Skip to main content
Top
Published in: Diabetologia 8/2003

01-08-2003 | Review

Insulin granule dynamics in pancreatic beta cells

Authors: Dr. P. Rorsman, E. Renström

Published in: Diabetologia | Issue 8/2003

Login to get access

Abstract

Glucose-induced insulin secretion in response to a step increase in blood glucose concentrations follows a biphasic time course consisting of a rapid and transient first phase followed by a slowly developing and sustained second phase. Because Type 2 diabetes involves defects of insulin secretion, manifested as a loss of first phase and a reduction of second phase, it is important to understand the cellular mechanisms underlying biphasic insulin secretion. Insulin release involves the packaging of insulin in small (diameter ≈0.3 µm) secretory granules, the trafficking of these granules to the plasma membrane, the exocytotic fusion of the granules with the plasma membrane and eventually the retrieval of the secreted membranes by endocytosis. Until recently, studies on insulin secretion have been confined to the appearance of insulin in the extracellular space and the cellular events preceding exocytosis have been inaccessible to more detailed analysis. Evidence from a variety of secretory tissues, including pancreatic islet cells suggests, however, that the secretory granules can be functionally divided into distinct pools that are distinguished by their release competence and/or proximity to the plasma membrane. The introduction of fluorescent proteins that can be targeted to the secretory granules, in combination with the advent of new techniques that allow real-time imaging of granule trafficking in living cells (granule dynamics), has led to an explosion of our knowledge of the pre-exocytotic and post-exocytotic processes in the beta cell. Here we discuss these observations in relation to previous functional and ultra-structural data as well as the secretory defects of Type 2 diabetes.
Literature
1.
go back to reference Dean PM (1973) Ultrastructural morphometry of the pancreatic β-cell. Diabetologia 9:115–119PubMed Dean PM (1973) Ultrastructural morphometry of the pancreatic β-cell. Diabetologia 9:115–119PubMed
2.
go back to reference Olofsson CS, Göpel SO, Barg S et al. (2002) Fast insulin secretion reflects exocytosis of docked granules in mouse pancreatic B-cells. Pflugers Arch 444:43–51CrossRefPubMed Olofsson CS, Göpel SO, Barg S et al. (2002) Fast insulin secretion reflects exocytosis of docked granules in mouse pancreatic B-cells. Pflugers Arch 444:43–51CrossRefPubMed
3.
go back to reference Orci L, Malaisse-Lagae F, Ravazzola M, Amherdt M, Renold AE (1973) Exocytosis-endocytosis coupling in the pancreatic beta cell. Science 181:561–562PubMed Orci L, Malaisse-Lagae F, Ravazzola M, Amherdt M, Renold AE (1973) Exocytosis-endocytosis coupling in the pancreatic beta cell. Science 181:561–562PubMed
4.
go back to reference Orci L, Amherdt M, Malaisse-Lagae F, Rouiller C, Renold AE (1973) Insulin release by emiocytosis: demonstration with freeze-etching technique. Science 179:82–84PubMed Orci L, Amherdt M, Malaisse-Lagae F, Rouiller C, Renold AE (1973) Insulin release by emiocytosis: demonstration with freeze-etching technique. Science 179:82–84PubMed
5.
go back to reference Wollheim CB, Sharp GW (1981) Regulation of insulin release by calcium. Physiol Rev 61:914–973PubMed Wollheim CB, Sharp GW (1981) Regulation of insulin release by calcium. Physiol Rev 61:914–973PubMed
6.
go back to reference Ämmälä C, Ashcroft FM, Rorsman P (1993) Calcium-independent potentiation of insulin release by cyclic AMP in single β-cells. Nature 363:356–358PubMed Ämmälä C, Ashcroft FM, Rorsman P (1993) Calcium-independent potentiation of insulin release by cyclic AMP in single β-cells. Nature 363:356–358PubMed
7.
go back to reference Neher E, Marty A (1982) Discrete changes of cell membrane capacitance observed under conditions of enhanced secretion in bovine adrenal chromaffin cells. Proc Natl Acad Sci USA 79:6712–6716PubMed Neher E, Marty A (1982) Discrete changes of cell membrane capacitance observed under conditions of enhanced secretion in bovine adrenal chromaffin cells. Proc Natl Acad Sci USA 79:6712–6716PubMed
8.
go back to reference Wightman RM, Jankowski JA, Kennedy RT et al. (1991) Temporally resolved catecholamine spikes correspond to single vesicle release from individual chromaffin cells. Proc Natl Acad Sci USA 88:10754–10758PubMed Wightman RM, Jankowski JA, Kennedy RT et al. (1991) Temporally resolved catecholamine spikes correspond to single vesicle release from individual chromaffin cells. Proc Natl Acad Sci USA 88:10754–10758PubMed
9.
go back to reference Steyer JA, Horstmann H, Almers W (1997) Transport, docking and exocytosis of single secretory granules in live chromaffin cells. Nature 388:474–478PubMed Steyer JA, Horstmann H, Almers W (1997) Transport, docking and exocytosis of single secretory granules in live chromaffin cells. Nature 388:474–478PubMed
10.
go back to reference Lang T, Wacker I, Steyer J et al. (1997) Ca2+-triggered peptide secretion in single cells imaged with green fluorescent protein and evanescent-wave microscopy. Neuron 18:857–863PubMed Lang T, Wacker I, Steyer J et al. (1997) Ca2+-triggered peptide secretion in single cells imaged with green fluorescent protein and evanescent-wave microscopy. Neuron 18:857–863PubMed
11.
go back to reference Henquin JC, Meissner HP (1984) Significance of ionic fluxes and changes in membrane potential for stimulus-secretion coupling in pancreatic B-cells. Experientia 40:1043–1052PubMed Henquin JC, Meissner HP (1984) Significance of ionic fluxes and changes in membrane potential for stimulus-secretion coupling in pancreatic B-cells. Experientia 40:1043–1052PubMed
12.
go back to reference Ashcroft FM, Rorsman P (1989) Electrophysiology of the pancreatic β-cell. Prog Biophys Mol Biol 54:87–143PubMed Ashcroft FM, Rorsman P (1989) Electrophysiology of the pancreatic β-cell. Prog Biophys Mol Biol 54:87–143PubMed
13.
go back to reference Valdeolmillos M, Santos RM, Contreras D, Soria B, Rosario LM (1989) Glucose-induced oscillations of intracellular Ca2+ concentration resembling bursting electrical activity in single mouse islets of Langerhans. FEBS Lett 259:19–23CrossRefPubMed Valdeolmillos M, Santos RM, Contreras D, Soria B, Rosario LM (1989) Glucose-induced oscillations of intracellular Ca2+ concentration resembling bursting electrical activity in single mouse islets of Langerhans. FEBS Lett 259:19–23CrossRefPubMed
14.
go back to reference Gilon P, Shepherd RM, Henquin JC (1993) Oscillations of secretion driven by oscillations of cytoplasmic Ca2+ as evidences in single pancreatic islets. J Biol Chem 268:22265–22268PubMed Gilon P, Shepherd RM, Henquin JC (1993) Oscillations of secretion driven by oscillations of cytoplasmic Ca2+ as evidences in single pancreatic islets. J Biol Chem 268:22265–22268PubMed
15.
go back to reference Barbosa RM, Silva AM, Tome AR, Stamford JA, Santos RM, Rosario LM (1998) Control of pulsatile 5-HT/insulin secretion from single mouse pancreatic islets by intracellular calcium dynamics. J Physiol 510:135–143PubMed Barbosa RM, Silva AM, Tome AR, Stamford JA, Santos RM, Rosario LM (1998) Control of pulsatile 5-HT/insulin secretion from single mouse pancreatic islets by intracellular calcium dynamics. J Physiol 510:135–143PubMed
16.
go back to reference Bergsten P (1995) Slow and fast oscillations of cytoplasmic Ca2+ in pancreatic islets correspond to pulsatile insulin release. Am J Physiol 268:E282–E287 Bergsten P (1995) Slow and fast oscillations of cytoplasmic Ca2+ in pancreatic islets correspond to pulsatile insulin release. Am J Physiol 268:E282–E287
17.
go back to reference Göpel S, Kanno T, Barg S, Galvanovskis J, Rorsman P (1999) Voltage-gated and resting membrane currents recorded from B-cells in intact mouse pancreatic islets. J Physiol 521:717–728PubMed Göpel S, Kanno T, Barg S, Galvanovskis J, Rorsman P (1999) Voltage-gated and resting membrane currents recorded from B-cells in intact mouse pancreatic islets. J Physiol 521:717–728PubMed
18.
go back to reference Ämmälä C, Eliasson L, Bokvist K, Larsson O, Ashcroft FM, Rorsman P (1993) Exocytosis elicited by action potentials and voltage-clamp calcium currents in individual mouse pancreatic B-cells. J Physiol 472:665–688PubMed Ämmälä C, Eliasson L, Bokvist K, Larsson O, Ashcroft FM, Rorsman P (1993) Exocytosis elicited by action potentials and voltage-clamp calcium currents in individual mouse pancreatic B-cells. J Physiol 472:665–688PubMed
19.
go back to reference Barg S, Ma X, Eliasson L et al. (2001) Fast exocytosis with few Ca2+ channels in insulin-secreting mouse pancreatic B cells. Biophys J 81:3308–3323PubMed Barg S, Ma X, Eliasson L et al. (2001) Fast exocytosis with few Ca2+ channels in insulin-secreting mouse pancreatic B cells. Biophys J 81:3308–3323PubMed
20.
go back to reference Wiser O, Trus M, Hernandez A et al. (1999) The voltage sensitive Lc-type Ca2+ channel is functionally coupled to the exocytotic machinery. Proc Natl Acad Sci USA 96:248–253CrossRefPubMed Wiser O, Trus M, Hernandez A et al. (1999) The voltage sensitive Lc-type Ca2+ channel is functionally coupled to the exocytotic machinery. Proc Natl Acad Sci USA 96:248–253CrossRefPubMed
21.
go back to reference Curry DL, Bennett LL, Grodsky GM (1968) Dynamics of insulin secretion by the perfused rat pancreas. Endocrinology 83:572–584PubMed Curry DL, Bennett LL, Grodsky GM (1968) Dynamics of insulin secretion by the perfused rat pancreas. Endocrinology 83:572–584PubMed
22.
go back to reference Anello M, Gilon P, Henquin JC (1999) Alterations of insulin secretion from mouse islets treated with sulphonylureas: perturbations of Ca2+ regulation prevail over changes in insulin content. Br J Pharmacol 127:1883–1891PubMed Anello M, Gilon P, Henquin JC (1999) Alterations of insulin secretion from mouse islets treated with sulphonylureas: perturbations of Ca2+ regulation prevail over changes in insulin content. Br J Pharmacol 127:1883–1891PubMed
23.
go back to reference Bratanova-Tochkova TK, Cheng H, Daniel S et al. (2002) Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion. Diabetes 51 [Suppl 1]:S83–S90 Bratanova-Tochkova TK, Cheng H, Daniel S et al. (2002) Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion. Diabetes 51 [Suppl 1]:S83–S90
24.
go back to reference Grodsky GM (1994) An update on implications of phsic insulin secretion. In: Flatt PR, Lenzen S (eds) Insulin secretion and pancreatic B-cell research. Smith Gordon, London, pp 421–430 Grodsky GM (1994) An update on implications of phsic insulin secretion. In: Flatt PR, Lenzen S (eds) Insulin secretion and pancreatic B-cell research. Smith Gordon, London, pp 421–430
25.
go back to reference Henquin JC (2000) Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes 49:1751–1760PubMed Henquin JC (2000) Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes 49:1751–1760PubMed
26.
go back to reference Westerlund J, Bergsten P (2001) Glucose metabolism and pulsatile insulin release from isolated islets. Diabetes 50:1785–1790PubMed Westerlund J, Bergsten P (2001) Glucose metabolism and pulsatile insulin release from isolated islets. Diabetes 50:1785–1790PubMed
27.
go back to reference Neher E (1998) Vesicle pools and Ca2+ microdomains: new tools for understanding their roles in neurotransmitter release. Neuron 20:389–399PubMed Neher E (1998) Vesicle pools and Ca2+ microdomains: new tools for understanding their roles in neurotransmitter release. Neuron 20:389–399PubMed
28.
go back to reference Gentet LJ, Stuart GJ, Clements JD (2000) Direct measurement of specific membrane capacitance in neurons. Biophys J 79:314–320PubMed Gentet LJ, Stuart GJ, Clements JD (2000) Direct measurement of specific membrane capacitance in neurons. Biophys J 79:314–320PubMed
29.
go back to reference Reetz A, Solimena M, Matteoli M, Folli F, Takei K, De Camilli P (1991) GABA and pancreatic beta-cells: colocalization of glutamic acid decarboxylase (GAD) and GABA with synaptic-like microvesicles suggests their role in GABA storage and secretion. Embo J 10:1275–1284PubMed Reetz A, Solimena M, Matteoli M, Folli F, Takei K, De Camilli P (1991) GABA and pancreatic beta-cells: colocalization of glutamic acid decarboxylase (GAD) and GABA with synaptic-like microvesicles suggests their role in GABA storage and secretion. Embo J 10:1275–1284PubMed
30.
go back to reference Kasai H (1999) Comparative biology of Ca2+-dependent exocytosis: implications of kinetic diversity for secretory function. Trends Neurosci 22:88–93CrossRefPubMed Kasai H (1999) Comparative biology of Ca2+-dependent exocytosis: implications of kinetic diversity for secretory function. Trends Neurosci 22:88–93CrossRefPubMed
31.
go back to reference Borgonovo B, Cocucci E, Racchetti G, Podini P, Bachi A, Meldolesi J (2002) Regulated exocytosis: a novel, widely expressed system. Nat Cell Biol 4:955–962CrossRefPubMed Borgonovo B, Cocucci E, Racchetti G, Podini P, Bachi A, Meldolesi J (2002) Regulated exocytosis: a novel, widely expressed system. Nat Cell Biol 4:955–962CrossRefPubMed
32.
go back to reference Amatore C, Bouret Y, Travis ER, Wightman RM (2000) Adrenaline release by chromaffin cells: constrained swelling of the vesicle matrix leads to full fusion. Angew Chem Int Ed Engl 39:1952–1955CrossRefPubMed Amatore C, Bouret Y, Travis ER, Wightman RM (2000) Adrenaline release by chromaffin cells: constrained swelling of the vesicle matrix leads to full fusion. Angew Chem Int Ed Engl 39:1952–1955CrossRefPubMed
33.
go back to reference Smith PA, Duchen MR, Ashcroft FM (1995) A fluorimetric and amperometric study of calcium and secretion in isolated mouse pancreatic beta-cells. Pflugers Arch 430:808–818PubMed Smith PA, Duchen MR, Ashcroft FM (1995) A fluorimetric and amperometric study of calcium and secretion in isolated mouse pancreatic beta-cells. Pflugers Arch 430:808–818PubMed
34.
go back to reference Zhou Z, Misler S (1996) Amperometric detection of quantal secretion from patch-clamped rat pancreatic beta-cells. J Biol Chem 271:270–277CrossRefPubMed Zhou Z, Misler S (1996) Amperometric detection of quantal secretion from patch-clamped rat pancreatic beta-cells. J Biol Chem 271:270–277CrossRefPubMed
35.
go back to reference Smith PA, Proks P, Ashcroft FM (1999) Quantal analysis of 5-hydroxytryptamine release from mouse pancreatic beta-cells. J Physiol 521:651–664PubMed Smith PA, Proks P, Ashcroft FM (1999) Quantal analysis of 5-hydroxytryptamine release from mouse pancreatic beta-cells. J Physiol 521:651–664PubMed
36.
go back to reference Bokvist K, Holmqvist M, Gromada J, Rorsman P (2000) Compound exocytosis in voltage-clamped mouse pancreatic beta-cells revealed by carbon fibre amperometry. Pflugers Arch 439:634–645CrossRefPubMed Bokvist K, Holmqvist M, Gromada J, Rorsman P (2000) Compound exocytosis in voltage-clamped mouse pancreatic beta-cells revealed by carbon fibre amperometry. Pflugers Arch 439:634–645CrossRefPubMed
37.
go back to reference Huang L, Shen H, Atkinson MA, Kennedy RT (1995) Detection of exocytosis at individual pancreatic beta cells by amperometry at a chemically modified microelectrode. Proc Natl Acad Sci USA 92:9608–9612PubMed Huang L, Shen H, Atkinson MA, Kennedy RT (1995) Detection of exocytosis at individual pancreatic beta cells by amperometry at a chemically modified microelectrode. Proc Natl Acad Sci USA 92:9608–9612PubMed
38.
go back to reference Aspinwall CA, Brooks SA, Kennedy RT, Lakey JR (1997) Effects of intravesicular H+ and extracellular H+ and Zn2+ on insulin secretion in pancreatic beta cells. J Biol Chem 272:31308–31314CrossRefPubMed Aspinwall CA, Brooks SA, Kennedy RT, Lakey JR (1997) Effects of intravesicular H+ and extracellular H+ and Zn2+ on insulin secretion in pancreatic beta cells. J Biol Chem 272:31308–31314CrossRefPubMed
39.
go back to reference Amatore C, Arbault S, Bonifas I, Bouret Y, Erard M, Guille M (2003) Dynamics of full fusion during vesicular exocytotic events: release of adrenaline by chromaffin cells. Chemphyschem 4:147–154CrossRefPubMed Amatore C, Arbault S, Bonifas I, Bouret Y, Erard M, Guille M (2003) Dynamics of full fusion during vesicular exocytotic events: release of adrenaline by chromaffin cells. Chemphyschem 4:147–154CrossRefPubMed
40.
go back to reference Travis ER, Wightman RM (1998) Spatio-temporal resolution of exocytosis from individual cells. Annu Rev Biophys Biomol Struct 27:77–103CrossRefPubMed Travis ER, Wightman RM (1998) Spatio-temporal resolution of exocytosis from individual cells. Annu Rev Biophys Biomol Struct 27:77–103CrossRefPubMed
41.
go back to reference Ohara-Imaizumi M, Nakamichi Y, Tanaka T, Katsuta H, Ishida H, Nagamatsu S (2002) Monitoring of exocytosis and endocytosis of insulin secretory granules in the pancreatic beta-cell line MIN6 using pH-sensitive green fluorescent protein (pHluorin) and confocal laser microscopy. Biochem J 363:73–80CrossRefPubMed Ohara-Imaizumi M, Nakamichi Y, Tanaka T, Katsuta H, Ishida H, Nagamatsu S (2002) Monitoring of exocytosis and endocytosis of insulin secretory granules in the pancreatic beta-cell line MIN6 using pH-sensitive green fluorescent protein (pHluorin) and confocal laser microscopy. Biochem J 363:73–80CrossRefPubMed
42.
43.
go back to reference Jahn R, Lang T, Sudhof TC (2003) Membrane fusion. Cell 112:519–533PubMed Jahn R, Lang T, Sudhof TC (2003) Membrane fusion. Cell 112:519–533PubMed
44.
go back to reference Lin RC, Scheller RH (2000) Mechanisms of synaptic vesicle exocytosis. Annu Rev Cell Dev Biol 16:19–49CrossRefPubMed Lin RC, Scheller RH (2000) Mechanisms of synaptic vesicle exocytosis. Annu Rev Cell Dev Biol 16:19–49CrossRefPubMed
45.
go back to reference Chapman ER (2002) Synaptotagmin: a Ca2+ sensor that triggers exocytosis? Nat Rev Mol Cell Biol 3:498–508 Chapman ER (2002) Synaptotagmin: a Ca2+ sensor that triggers exocytosis? Nat Rev Mol Cell Biol 3:498–508
46.
go back to reference Shin OH, Rizo J, Sudhof TC (2002) Synaptotagmin function in dense core vesicle exocytosis studied in cracked PC12 cells. Nat Neurosci 5:649–656PubMed Shin OH, Rizo J, Sudhof TC (2002) Synaptotagmin function in dense core vesicle exocytosis studied in cracked PC12 cells. Nat Neurosci 5:649–656PubMed
47.
go back to reference Sugita S, Shin OH, Han W, Lao Y, Sudhof TC (2002) Synaptotagmins form a hierarchy of exocytotic Ca2+ sensors with distinct Ca2+ affinities. Embo J 21:270–280CrossRefPubMed Sugita S, Shin OH, Han W, Lao Y, Sudhof TC (2002) Synaptotagmins form a hierarchy of exocytotic Ca2+ sensors with distinct Ca2+ affinities. Embo J 21:270–280CrossRefPubMed
48.
49.
go back to reference Lang J (1999) Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion. Eur J Biochem 259:3–17CrossRefPubMed Lang J (1999) Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion. Eur J Biochem 259:3–17CrossRefPubMed
50.
go back to reference Martin F, Moya F, Gutierrez LM, Reig JA, Soria B (1995) Role of syntaxin in mouse pancreatic beta cells. Diabetologia 38:860–863CrossRefPubMed Martin F, Moya F, Gutierrez LM, Reig JA, Soria B (1995) Role of syntaxin in mouse pancreatic beta cells. Diabetologia 38:860–863CrossRefPubMed
51.
go back to reference Martin F, Salinas E, Vazquez J, Soria B, Reig JA (1996) Inhibition of insulin release by synthetic peptides shows that the H3 region at the C-terminal domain of syntaxin-1 is crucial for Ca2+- but not for guanosine 5′-[gamma-thio]triphosphate-induced secretion. Biochem J 320:201–205PubMed Martin F, Salinas E, Vazquez J, Soria B, Reig JA (1996) Inhibition of insulin release by synthetic peptides shows that the H3 region at the C-terminal domain of syntaxin-1 is crucial for Ca2+- but not for guanosine 5′-[gamma-thio]triphosphate-induced secretion. Biochem J 320:201–205PubMed
52.
go back to reference Lang J, Fukuda M, Zhang H, Mikoshiba K, Wollheim CB (1997) The first C2 domain of synaptotagmin is required for exocytosis of insulin from pancreatic beta-cells: action of synaptotagmin at low micromolar calcium. Embo J 16:5837–5846CrossRefPubMed Lang J, Fukuda M, Zhang H, Mikoshiba K, Wollheim CB (1997) The first C2 domain of synaptotagmin is required for exocytosis of insulin from pancreatic beta-cells: action of synaptotagmin at low micromolar calcium. Embo J 16:5837–5846CrossRefPubMed
53.
go back to reference Brown H, Meister B, Deeney J et al. (2000) Synaptotagmin III isoform is compartmentalized in pancreatic beta-cells and has a functional role in exocytosis. Diabetes 49:383–391PubMed Brown H, Meister B, Deeney J et al. (2000) Synaptotagmin III isoform is compartmentalized in pancreatic beta-cells and has a functional role in exocytosis. Diabetes 49:383–391PubMed
54.
go back to reference Gut A, Kiraly CE, Fukuda M, Mikoshiba K, Wollheim CB, Lang J (2001) Expression and localisation of synaptotagmin isoforms in endocrine beta-cells: their function in insulin exocytosis. J Cell Sci 114:1709–1716PubMed Gut A, Kiraly CE, Fukuda M, Mikoshiba K, Wollheim CB, Lang J (2001) Expression and localisation of synaptotagmin isoforms in endocrine beta-cells: their function in insulin exocytosis. J Cell Sci 114:1709–1716PubMed
55.
go back to reference Bokvist K, Eliasson L, Ämmälä C, Renström E, Rorsman P (1995) Co-localization of L-type Ca2+ channels and insulin-containing secretory granules and its significance for the initiation of exocytosis in mouse pancreatic B-cells. EMBO J 14:50–57PubMed Bokvist K, Eliasson L, Ämmälä C, Renström E, Rorsman P (1995) Co-localization of L-type Ca2+ channels and insulin-containing secretory granules and its significance for the initiation of exocytosis in mouse pancreatic B-cells. EMBO J 14:50–57PubMed
56.
go back to reference Takahashi N, Kadowaki T, Yazaki Y, Miyashita Y, Kasai H (1997) Multiple exocytotic pathways in pancreatic beta cells. J Cell Biol 138:55–64CrossRefPubMed Takahashi N, Kadowaki T, Yazaki Y, Miyashita Y, Kasai H (1997) Multiple exocytotic pathways in pancreatic beta cells. J Cell Biol 138:55–64CrossRefPubMed
57.
go back to reference Iezzi M, Escher G, Meda P et al. (1999) Subcellular distribution and function of Rab3A, B, C, and D isoforms in insulin-secreting cells. Mol Endocrinol 13:202–212PubMed Iezzi M, Escher G, Meda P et al. (1999) Subcellular distribution and function of Rab3A, B, C, and D isoforms in insulin-secreting cells. Mol Endocrinol 13:202–212PubMed
58.
go back to reference Geppert M, Goda Y, Stevens CF, Südhof TC (1997) The small GTP-binding protein Rab3A regulates a late step in synaptic vesicle fusion. Nature 387:810–814 Geppert M, Goda Y, Stevens CF, Südhof TC (1997) The small GTP-binding protein Rab3A regulates a late step in synaptic vesicle fusion. Nature 387:810–814
59.
go back to reference Regazzi R, Ravazzola M, Iezzi M et al. (1996) Expression, localization and functional role of small GTPases of the Rab3 family in insulin-secreting cells. J Cell Sci 109:2265–2273PubMed Regazzi R, Ravazzola M, Iezzi M et al. (1996) Expression, localization and functional role of small GTPases of the Rab3 family in insulin-secreting cells. J Cell Sci 109:2265–2273PubMed
60.
go back to reference Coppola T, Perret-Menoud V, Luthi S, Farnsworth CC, Glomset JA, Regazzi R (1999) Disruption of Rab3-calmodulin interaction, but not other effector interactions, prevents Rab3 inhibition of exocytosis. Embo J 18:5885–5891CrossRefPubMed Coppola T, Perret-Menoud V, Luthi S, Farnsworth CC, Glomset JA, Regazzi R (1999) Disruption of Rab3-calmodulin interaction, but not other effector interactions, prevents Rab3 inhibition of exocytosis. Embo J 18:5885–5891CrossRefPubMed
61.
go back to reference Yaekura K, Julyan R, Wicksteed BL et al. (2003) Insulin secretory deficiency and glucose intolerance in Rab3A null mice. J Biol Chem 278:9715–9721CrossRefPubMed Yaekura K, Julyan R, Wicksteed BL et al. (2003) Insulin secretory deficiency and glucose intolerance in Rab3A null mice. J Biol Chem 278:9715–9721CrossRefPubMed
62.
go back to reference Iezzi M, Regazzi R, Wollheim CB (2000) The Rab3-interacting molecule RIM is expressed in pancreatic beta-cells and is implicated in insulin exocytosis. FEBS Lett 474:66–70CrossRefPubMed Iezzi M, Regazzi R, Wollheim CB (2000) The Rab3-interacting molecule RIM is expressed in pancreatic beta-cells and is implicated in insulin exocytosis. FEBS Lett 474:66–70CrossRefPubMed
63.
go back to reference Coppola T, Magnin-Luthi S, Perret-Menoud V, Gattesco S, Schiavo G, Regazzi R (2001) Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin. J Biol Chem 276:32756–32762CrossRefPubMed Coppola T, Magnin-Luthi S, Perret-Menoud V, Gattesco S, Schiavo G, Regazzi R (2001) Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin. J Biol Chem 276:32756–32762CrossRefPubMed
64.
go back to reference Schoch S, Castillo PE, Jo T et al. (2002) RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone. Nature 415:321–326CrossRefPubMed Schoch S, Castillo PE, Jo T et al. (2002) RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone. Nature 415:321–326CrossRefPubMed
65.
go back to reference Ozaki N, Shibasaki T, Kashima Y et al. (2000) cAMP-GEFII is a direct target of cAMP in regulated exocytosis. Nat Cell Biol 2:805–811CrossRefPubMed Ozaki N, Shibasaki T, Kashima Y et al. (2000) cAMP-GEFII is a direct target of cAMP in regulated exocytosis. Nat Cell Biol 2:805–811CrossRefPubMed
66.
go back to reference Eliasson L, Ma X, Renström E et al. (2003) SUR1 Regulates PKA-independent cAMP-induced Granule Priming in Mouse Pancreatic B-cells. J Gen Physiol 121:181–197CrossRefPubMed Eliasson L, Ma X, Renström E et al. (2003) SUR1 Regulates PKA-independent cAMP-induced Granule Priming in Mouse Pancreatic B-cells. J Gen Physiol 121:181–197CrossRefPubMed
67.
go back to reference Xu T, Rammner B, Margittai M, Artalejo AR, Neher E, Jahn R (1999) Inhibition of SNARE complex assembly differentially affects kinetic components of exocytosis. Cell 99:713–722PubMed Xu T, Rammner B, Margittai M, Artalejo AR, Neher E, Jahn R (1999) Inhibition of SNARE complex assembly differentially affects kinetic components of exocytosis. Cell 99:713–722PubMed
68.
go back to reference Rettig J, Neher E (2002) Emerging roles of presynaptic proteins in Ca++-triggered exocytosis. Science 298:781–785CrossRefPubMed Rettig J, Neher E (2002) Emerging roles of presynaptic proteins in Ca++-triggered exocytosis. Science 298:781–785CrossRefPubMed
69.
go back to reference Grodsky G, Landahl H, Curry D, Bennett L (1970) A two-compartmental model for insulin secretion. Adv Metab Disord 1[Suppl 1]:45–50 Grodsky G, Landahl H, Curry D, Bennett L (1970) A two-compartmental model for insulin secretion. Adv Metab Disord 1[Suppl 1]:45–50
70.
go back to reference O'Connor MD, Landahl H, Grodsky GM (1980) Comparison of storage- and signal-limited models of pancreatic insulin secretion. Am J Physiol 238:R378–389PubMed O'Connor MD, Landahl H, Grodsky GM (1980) Comparison of storage- and signal-limited models of pancreatic insulin secretion. Am J Physiol 238:R378–389PubMed
71.
go back to reference Renström E, Eliasson L, Rorsman P (1997) Protein kinase A-dependent and -independent stimulation of exocytosis by cAMP in mouse pancreatic B-cells. J Physiol 502:105–118PubMed Renström E, Eliasson L, Rorsman P (1997) Protein kinase A-dependent and -independent stimulation of exocytosis by cAMP in mouse pancreatic B-cells. J Physiol 502:105–118PubMed
72.
go back to reference Gromada J, Hoy M, Renström E et al. (1999) CaM kinase II-dependent mobilization of secretory granules underlies acetylcholine-induced stimulation of exocytosis in mouse pancreatic B-cells. J Physiol 518:745–759PubMed Gromada J, Hoy M, Renström E et al. (1999) CaM kinase II-dependent mobilization of secretory granules underlies acetylcholine-induced stimulation of exocytosis in mouse pancreatic B-cells. J Physiol 518:745–759PubMed
73.
go back to reference Rorsman P, Eliasson L, Renstrom E, Gromada J, Barg S, Göpel S (2000) The cell physiology of biphasic insulin secretion. News Physiol Sci 15:72–77PubMed Rorsman P, Eliasson L, Renstrom E, Gromada J, Barg S, Göpel S (2000) The cell physiology of biphasic insulin secretion. News Physiol Sci 15:72–77PubMed
74.
go back to reference Eddlestone GT, Oldham SB, Lipson LG, Premdas FH, Beigelman PM (1985) Electrical activity, cAMP concentration, and insulin release in mouse islets of Langerhans. Am J Physiol 248:C145–C153PubMed Eddlestone GT, Oldham SB, Lipson LG, Premdas FH, Beigelman PM (1985) Electrical activity, cAMP concentration, and insulin release in mouse islets of Langerhans. Am J Physiol 248:C145–C153PubMed
75.
go back to reference Barg S, Eliasson L, Renström E, Rorsman P (2002) A subset of 50 secretory granules in close contact with L-type Ca2+ channels accounts for first-phase insulin secretion in mouse beta-cells. Diabetes 51 [Suppl 1]:S74–S82 Barg S, Eliasson L, Renström E, Rorsman P (2002) A subset of 50 secretory granules in close contact with L-type Ca2+ channels accounts for first-phase insulin secretion in mouse beta-cells. Diabetes 51 [Suppl 1]:S74–S82
76.
go back to reference Dean PM, Matthews EK (1970) Glucose-induced electrical activity in pancreatic islet cells. J Physiol 210:255–264PubMed Dean PM, Matthews EK (1970) Glucose-induced electrical activity in pancreatic islet cells. J Physiol 210:255–264PubMed
77.
go back to reference Henquin JC, Ishiyama N, Nenquin M, Ravier MA, Jonas JC (2002) Signals and pools underlying biphasic insulin secretion. Diabetes 51 [Suppl 1]:S60–S67 Henquin JC, Ishiyama N, Nenquin M, Ravier MA, Jonas JC (2002) Signals and pools underlying biphasic insulin secretion. Diabetes 51 [Suppl 1]:S60–S67
78.
go back to reference Daniel S, Noda M, Straub SG, Sharp GW (1999) Identification of the docked granule pool responsible for the first phase of glucose-stimulated insulin secretion. Diabetes 48:1686–1690PubMed Daniel S, Noda M, Straub SG, Sharp GW (1999) Identification of the docked granule pool responsible for the first phase of glucose-stimulated insulin secretion. Diabetes 48:1686–1690PubMed
79.
go back to reference Ohara-Imaizumi M, Nakamichi Y, Tanaka T, Ishida H, Nagamatsu S (2002) Imaging exocytosis of single insulin secretory granules with evanescent wave microscopy: distinct behavior of granule motion in biphasic insulin release. J Biol Chem 277:3805–3808CrossRefPubMed Ohara-Imaizumi M, Nakamichi Y, Tanaka T, Ishida H, Nagamatsu S (2002) Imaging exocytosis of single insulin secretory granules with evanescent wave microscopy: distinct behavior of granule motion in biphasic insulin release. J Biol Chem 277:3805–3808CrossRefPubMed
80.
go back to reference Renstrom E, Ding WG, Bokvist K, Rorsman P (1996) Neurotransmitter-induced inhibition of exocytosis in insulin-secreting beta cells by activation of calcineurin. Neuron 17:513–522PubMed Renstrom E, Ding WG, Bokvist K, Rorsman P (1996) Neurotransmitter-induced inhibition of exocytosis in insulin-secreting beta cells by activation of calcineurin. Neuron 17:513–522PubMed
81.
go back to reference Takahashi N, Kadowaki T, Yazaki Y, Ellis-Davies GC, Miyashita Y, Kasai H (1999) Post-priming actions of ATP on Ca2+-dependent exocytosis in pancreatic beta cells. Proc Natl Acad Sci USA 96:760–765CrossRefPubMed Takahashi N, Kadowaki T, Yazaki Y, Ellis-Davies GC, Miyashita Y, Kasai H (1999) Post-priming actions of ATP on Ca2+-dependent exocytosis in pancreatic beta cells. Proc Natl Acad Sci USA 96:760–765CrossRefPubMed
82.
go back to reference Ekholm R, Ericson LE, Lundquist I (1971) Monoamines in the pancreatic islets of the mouse. Subcellular localization of 5-hydroxytryptamine by electron microscopic autoradiography. Diabetologia 7:339–348PubMed Ekholm R, Ericson LE, Lundquist I (1971) Monoamines in the pancreatic islets of the mouse. Subcellular localization of 5-hydroxytryptamine by electron microscopic autoradiography. Diabetologia 7:339–348PubMed
83.
go back to reference Eliasson L, Proks P, Ämmälä C et al. (1996) Endocytosis of secretory granules in mouse pancreatic beta-cells evoked by transient elevation of cytosolic calcium. J Physiol 493:755–767PubMed Eliasson L, Proks P, Ämmälä C et al. (1996) Endocytosis of secretory granules in mouse pancreatic beta-cells evoked by transient elevation of cytosolic calcium. J Physiol 493:755–767PubMed
84.
go back to reference Takahashi N, Kishimoto T, Nemoto T, Kadowaki T, Kasai H (2002) Fusion pore dynamics and insulin granule exocytosis in the pancreatic islet. Science 297:1349–1352CrossRefPubMed Takahashi N, Kishimoto T, Nemoto T, Kadowaki T, Kasai H (2002) Fusion pore dynamics and insulin granule exocytosis in the pancreatic islet. Science 297:1349–1352CrossRefPubMed
85.
go back to reference Albillos A, Dernick G, Horstmann H, Almers W, Alvarez de Toledo G, Lindau M (1997) The exocytotic event in chromaffin cells revealed by patch amperometry. Nature 389:509–512CrossRefPubMed Albillos A, Dernick G, Horstmann H, Almers W, Alvarez de Toledo G, Lindau M (1997) The exocytotic event in chromaffin cells revealed by patch amperometry. Nature 389:509–512CrossRefPubMed
86.
go back to reference Pouli AE, Emmanouilidou E, Zhao C, Wasmeier C, Hutton JC, Rutter GA (1998) Secretory-granule dynamics visualized in vivo with a phogrin-green fluorescent protein chimaera. Biochem J 333:193–199PubMed Pouli AE, Emmanouilidou E, Zhao C, Wasmeier C, Hutton JC, Rutter GA (1998) Secretory-granule dynamics visualized in vivo with a phogrin-green fluorescent protein chimaera. Biochem J 333:193–199PubMed
87.
go back to reference Tsuboi T, Zhao C, Terakawa S, Rutter GA (2000) Simultaneous evanescent wave imaging of insulin vesicle membrane and cargo during a single exocytotic event. Curr Biol 10:1307–1310CrossRefPubMed Tsuboi T, Zhao C, Terakawa S, Rutter GA (2000) Simultaneous evanescent wave imaging of insulin vesicle membrane and cargo during a single exocytotic event. Curr Biol 10:1307–1310CrossRefPubMed
88.
go back to reference Barg S, Olofsson CS, Schriever-Abeln J et al. (2002) Delay between fusion pore opening and peptide release from large dense-core vesicles in neuroendocrine cells. Neuron 33:287–299PubMed Barg S, Olofsson CS, Schriever-Abeln J et al. (2002) Delay between fusion pore opening and peptide release from large dense-core vesicles in neuroendocrine cells. Neuron 33:287–299PubMed
89.
go back to reference Watkins S, Geng X, Li L, Papworth G, Robbins PD, Drain P (2002) Imaging secretory vesicles by fluorescent protein insertion in propeptide rather than mature secreted peptide. Traffic 3:461–471CrossRefPubMed Watkins S, Geng X, Li L, Papworth G, Robbins PD, Drain P (2002) Imaging secretory vesicles by fluorescent protein insertion in propeptide rather than mature secreted peptide. Traffic 3:461–471CrossRefPubMed
90.
go back to reference Varadi A, Ainscow EK, Allan VJ, Rutter GA (2002) Involvement of conventional kinesin in glucose-stimulated secretory granule movements and exocytosis in clonal pancreatic beta-cells. J Cell Sci 115:4177–4189CrossRefPubMed Varadi A, Ainscow EK, Allan VJ, Rutter GA (2002) Involvement of conventional kinesin in glucose-stimulated secretory granule movements and exocytosis in clonal pancreatic beta-cells. J Cell Sci 115:4177–4189CrossRefPubMed
91.
go back to reference Amatore C, Bouret Y, Travis ER, Wightman RM (2000) Interplay between membrane dynamics, diffusion and swelling pressure governs individual vesicular exocytotic events during release of adrenaline by chromaffin cells. Biochimie 82:481–496CrossRefPubMed Amatore C, Bouret Y, Travis ER, Wightman RM (2000) Interplay between membrane dynamics, diffusion and swelling pressure governs individual vesicular exocytotic events during release of adrenaline by chromaffin cells. Biochimie 82:481–496CrossRefPubMed
92.
go back to reference Tsuboi T, Rutter GA (2003) Multiple forms of "kiss-and-run" exocytosis revealed by evanescent wave microscopy. Curr Biol 13:563–567CrossRefPubMed Tsuboi T, Rutter GA (2003) Multiple forms of "kiss-and-run" exocytosis revealed by evanescent wave microscopy. Curr Biol 13:563–567CrossRefPubMed
93.
go back to reference Hutton JC, Peshavaria M, Tooke NE (1983) 5-Hydroxytryptamine transport in cells and secretory granules from a transplantable rat insulinoma. Biochem J 210:803–810PubMed Hutton JC, Peshavaria M, Tooke NE (1983) 5-Hydroxytryptamine transport in cells and secretory granules from a transplantable rat insulinoma. Biochem J 210:803–810PubMed
94.
go back to reference Hutton JC, Penn EJ, Peshavaria M (1983) Low-molecular-weight constituents of isolated insulin-secretory granules. Bivalent cations, adenine nucleotides and inorganic phosphate. Biochem J 210:297–305PubMed Hutton JC, Penn EJ, Peshavaria M (1983) Low-molecular-weight constituents of isolated insulin-secretory granules. Bivalent cations, adenine nucleotides and inorganic phosphate. Biochem J 210:297–305PubMed
95.
go back to reference Maechler P, Wollheim CB (1999) Mitochondrial glutamate acts as a messenger in glucose-induced insulin exocytosis. Nature 402:685–689PubMed Maechler P, Wollheim CB (1999) Mitochondrial glutamate acts as a messenger in glucose-induced insulin exocytosis. Nature 402:685–689PubMed
96.
go back to reference Ericson LE, Hеkanson R, Lundquist I (1977) Accumulation of dopamine in mouse pancreatic B-cells following injection of L-DOPA. Localization to secretory granules and inhibition of insulin secretion. Diabetologia 13:117–124PubMed Ericson LE, Hеkanson R, Lundquist I (1977) Accumulation of dopamine in mouse pancreatic B-cells following injection of L-DOPA. Localization to secretory granules and inhibition of insulin secretion. Diabetologia 13:117–124PubMed
97.
go back to reference Eliasson L, Renström E, Ding WG, Proks P, Rorsman P (1997) Rapid ATP-dependent priming of secretory granules precedes Ca2+-induced exocytosis in mouse pancreatic B-cells. J Physiol 503:399–412PubMed Eliasson L, Renström E, Ding WG, Proks P, Rorsman P (1997) Rapid ATP-dependent priming of secretory granules precedes Ca2+-induced exocytosis in mouse pancreatic B-cells. J Physiol 503:399–412PubMed
98.
go back to reference Somers G, Blondel B, Orci L, Malaisse WJ (1979) Motile events in pancreatic endocrine cells. Endocrinology 104:255–264PubMed Somers G, Blondel B, Orci L, Malaisse WJ (1979) Motile events in pancreatic endocrine cells. Endocrinology 104:255–264PubMed
99.
go back to reference Bertrand G, Ishiyama N, Nenquin M, Ravier MA, Henquin JC (2002) The elevation of glutamate content and the amplification of insulin secretion in glucose-stimulated pancreatic islets are not causally related. J Biol Chem 277:32883–32891CrossRefPubMed Bertrand G, Ishiyama N, Nenquin M, Ravier MA, Henquin JC (2002) The elevation of glutamate content and the amplification of insulin secretion in glucose-stimulated pancreatic islets are not causally related. J Biol Chem 277:32883–32891CrossRefPubMed
100.
go back to reference Aizawa T, Sato Y, Komatsu M, Hashizume K (1992) ATP-sensitive K+ channel-independent, insulinotropic action of glucose in the B-cells. Endocr Regul 26:159–162PubMed Aizawa T, Sato Y, Komatsu M, Hashizume K (1992) ATP-sensitive K+ channel-independent, insulinotropic action of glucose in the B-cells. Endocr Regul 26:159–162PubMed
101.
go back to reference Baukrowitz T, Fakler B (2000) KATP channels gated by intracellular nucleotides and phospholipids. Eur J Biochem 267:5842–5848CrossRefPubMed Baukrowitz T, Fakler B (2000) KATP channels gated by intracellular nucleotides and phospholipids. Eur J Biochem 267:5842–5848CrossRefPubMed
102.
go back to reference Ashcroft FM, Gribble FM (1999) ATP-sensitive K+ channels and insulin secretion: their role in health and disease. Diabetologia 42:903–919PubMed Ashcroft FM, Gribble FM (1999) ATP-sensitive K+ channels and insulin secretion: their role in health and disease. Diabetologia 42:903–919PubMed
103.
go back to reference Bryan J, Aguilar-Bryan L (1999) Sulfonylurea receptors: ABC transporters that regulate ATP-sensitive K+ channels. Biochim Biophys Acta 1461:285–303CrossRefPubMed Bryan J, Aguilar-Bryan L (1999) Sulfonylurea receptors: ABC transporters that regulate ATP-sensitive K+ channels. Biochim Biophys Acta 1461:285–303CrossRefPubMed
104.
go back to reference Nichols CG, Koster JC (2002) Diabetes and insulin secretion: whither KATP? Am J Physiol Endocrinol Metab 283:E403–E412 Nichols CG, Koster JC (2002) Diabetes and insulin secretion: whither KATP? Am J Physiol Endocrinol Metab 283:E403–E412
105.
go back to reference Malaisse WJ, Herchuelz, A (1982) Nutritional regulation of K+ conductance: an unsettled aspect of pancreatic B cell physiology. In: Litwack G (ed.) Biochemical actions of hormones. Academic Press, New York, pp 69–92 Malaisse WJ, Herchuelz, A (1982) Nutritional regulation of K+ conductance: an unsettled aspect of pancreatic B cell physiology. In: Litwack G (ed.) Biochemical actions of hormones. Academic Press, New York, pp 69–92
106.
go back to reference Detimary P, Dejonghe S, Ling Z, Pipeleers D, Schuit F, Henquin JC (1998) The changes in adenine nucleotides measured in glucose-stimulated rodent islets occur in beta cells but not in alpha cells and are also observed in human islets. J Biol Chem 273:33905–33908PubMed Detimary P, Dejonghe S, Ling Z, Pipeleers D, Schuit F, Henquin JC (1998) The changes in adenine nucleotides measured in glucose-stimulated rodent islets occur in beta cells but not in alpha cells and are also observed in human islets. J Biol Chem 273:33905–33908PubMed
107.
go back to reference Olsen HL, Hoy M, Zhang W et al. (2003) Phosphatidylinositol 4-kinase serves as a metabolic sensor and regulates priming of secretory granules in pancreatic beta cells. Proc Natl Acad Sci USA 100:5187–5192CrossRefPubMed Olsen HL, Hoy M, Zhang W et al. (2003) Phosphatidylinositol 4-kinase serves as a metabolic sensor and regulates priming of secretory granules in pancreatic beta cells. Proc Natl Acad Sci USA 100:5187–5192CrossRefPubMed
108.
go back to reference Ghosh A, Ronner P, Cheong E, Khalid P, Matschinsky FM (1991) The role of ATP and free ADP in metabolic coupling during fuel-stimulated insulin release from islet beta-cells in the isolated perfused rat pancreas. J Biol Chem 266:22887–22892PubMed Ghosh A, Ronner P, Cheong E, Khalid P, Matschinsky FM (1991) The role of ATP and free ADP in metabolic coupling during fuel-stimulated insulin release from islet beta-cells in the isolated perfused rat pancreas. J Biol Chem 266:22887–22892PubMed
109.
go back to reference Barg S, Huang P, Eliasson L et al. (2001) Priming of insulin granules for exocytosis by granular Cl– uptake and acidification. J Cell Sci 114:2145–2154PubMed Barg S, Huang P, Eliasson L et al. (2001) Priming of insulin granules for exocytosis by granular Cl uptake and acidification. J Cell Sci 114:2145–2154PubMed
110.
go back to reference Thevenod F (2002) Ion channels in secretory granules of the pancreas and their role in exocytosis and release of secretory proteins. Am J Physiol Cell Physiol 283:C651–C672PubMed Thevenod F (2002) Ion channels in secretory granules of the pancreas and their role in exocytosis and release of secretory proteins. Am J Physiol Cell Physiol 283:C651–C672PubMed
111.
go back to reference Galli T, Haucke V (2001) Cycling of synaptic vesicles: how far? How fast! Sci STKE 2001:RE1 Galli T, Haucke V (2001) Cycling of synaptic vesicles: how far? How fast! Sci STKE 2001:RE1
112.
113.
go back to reference Taraska JW, Perrais D, Ohara-Imaizumi M, Nagamatsu S, Almers W (2003) Secretory granules are recaptured largely intact after stimulated exocytosis in cultured endocrine cells. Proc Natl Acad Sci USA 100:2070–2075CrossRefPubMed Taraska JW, Perrais D, Ohara-Imaizumi M, Nagamatsu S, Almers W (2003) Secretory granules are recaptured largely intact after stimulated exocytosis in cultured endocrine cells. Proc Natl Acad Sci USA 100:2070–2075CrossRefPubMed
114.
go back to reference Neves G, Lagnado L (1999) The kinetics of exocytosis and endocytosis in the synaptic terminal of goldfish retinal bipolar cells. J Physiol 515:181–202PubMed Neves G, Lagnado L (1999) The kinetics of exocytosis and endocytosis in the synaptic terminal of goldfish retinal bipolar cells. J Physiol 515:181–202PubMed
115.
go back to reference Hosker JP, Rudenski AS, Burnett MA, Matthews DR, Turner RC (1989) Similar reduction of first- and second-phase B-cell responses at three different glucose levels in type II diabetes and the effect of gliclazide therapy. Metabolism 38:767–772PubMed Hosker JP, Rudenski AS, Burnett MA, Matthews DR, Turner RC (1989) Similar reduction of first- and second-phase B-cell responses at three different glucose levels in type II diabetes and the effect of gliclazide therapy. Metabolism 38:767–772PubMed
116.
go back to reference Gromada J, Holst JJ, Rorsman P (1998) Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1. Pflugers Arch 435:583–594PubMed Gromada J, Holst JJ, Rorsman P (1998) Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1. Pflugers Arch 435:583–594PubMed
117.
go back to reference Efendic S, Wajngot A, Vranic M (1985) Increased activity of the glucose cycle in the liver: early characteristic of type 2 diabetes. Proc Natl Acad Sci USA 82:2965–2969PubMed Efendic S, Wajngot A, Vranic M (1985) Increased activity of the glucose cycle in the liver: early characteristic of type 2 diabetes. Proc Natl Acad Sci USA 82:2965–2969PubMed
118.
go back to reference Maechler P, Wollheim CB (2001) Mitochondrial function in normal and diabetic beta-cells. Nature 414:807–812PubMed Maechler P, Wollheim CB (2001) Mitochondrial function in normal and diabetic beta-cells. Nature 414:807–812PubMed
119.
go back to reference Chan CB, De Leo D, Joseph JW et al. (2001) Increased uncoupling protein-2 levels in beta-cells are associated with impaired glucose-stimulated insulin secretion: mechanism of action. Diabetes 50:1302–1310PubMed Chan CB, De Leo D, Joseph JW et al. (2001) Increased uncoupling protein-2 levels in beta-cells are associated with impaired glucose-stimulated insulin secretion: mechanism of action. Diabetes 50:1302–1310PubMed
120.
go back to reference Lameloise N, Muzzin P, Prentki M, Assimacopoulos-Jeannet F (2001) Uncoupling protein 2: a possible link between fatty acid excess and impaired glucose-induced insulin secretion? Diabetes 50:803–809 Lameloise N, Muzzin P, Prentki M, Assimacopoulos-Jeannet F (2001) Uncoupling protein 2: a possible link between fatty acid excess and impaired glucose-induced insulin secretion? Diabetes 50:803–809
121.
go back to reference Nagamatsu S, Nakamichi Y, Yamamura C et al. (1999) Decreased expression of t-SNARE, syntaxin 1, and SNAP-25 in pancreatic beta-cells is involved in impaired insulin secretion from diabetic GK rat islets: restoration of decreased t-SNARE proteins improves impaired insulin secretion. Diabetes 48:2367–2373PubMed Nagamatsu S, Nakamichi Y, Yamamura C et al. (1999) Decreased expression of t-SNARE, syntaxin 1, and SNAP-25 in pancreatic beta-cells is involved in impaired insulin secretion from diabetic GK rat islets: restoration of decreased t-SNARE proteins improves impaired insulin secretion. Diabetes 48:2367–2373PubMed
122.
go back to reference Zhang W, Khan A, Ostenson CG, Berggren PO, Efendic S, Meister B (2002) Down-regulated expression of exocytotic proteins in pancreatic islets of diabetic GK rats. Biochem Biophys Res Commun 291:1038–1044CrossRefPubMed Zhang W, Khan A, Ostenson CG, Berggren PO, Efendic S, Meister B (2002) Down-regulated expression of exocytotic proteins in pancreatic islets of diabetic GK rats. Biochem Biophys Res Commun 291:1038–1044CrossRefPubMed
123.
go back to reference Tsunoda K, Sanke T, Nakagawa T, Furuta H, Nanjo K (2001) Single nucleotide polymorphism (D68D, T to C) in the syntaxin 1A gene correlates to age at onset and insulin requirement in Type II diabetic patients. Diabetologia 44:2092–2097CrossRefPubMed Tsunoda K, Sanke T, Nakagawa T, Furuta H, Nanjo K (2001) Single nucleotide polymorphism (D68D, T to C) in the syntaxin 1A gene correlates to age at onset and insulin requirement in Type II diabetic patients. Diabetologia 44:2092–2097CrossRefPubMed
124.
go back to reference Bell GI, Polonsky KS (2001) Diabetes mellitus and genetically programmed defects in beta-cell function. Nature 414:788–791PubMed Bell GI, Polonsky KS (2001) Diabetes mellitus and genetically programmed defects in beta-cell function. Nature 414:788–791PubMed
125.
126.
go back to reference Froguel P, Velho G (2001) Genetic determinants of type 2 diabetes. Recent Prog Horm Res 56:91–105PubMed Froguel P, Velho G (2001) Genetic determinants of type 2 diabetes. Recent Prog Horm Res 56:91–105PubMed
127.
go back to reference Ward WK, Bolgiano DC, McKnight B, Halter JB, Porte D Jr (1984) Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Invest 74:1318–1328PubMed Ward WK, Bolgiano DC, McKnight B, Halter JB, Porte D Jr (1984) Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Invest 74:1318–1328PubMed
128.
go back to reference Smith PA, Sakura H, Coles B, Gummerson N, Proks P, Ashcroft FM (1997) Electrogenic arginine transport mediates stimulus-secretion coupling in mouse pancreatic beta-cells. J Physiol 499:625–635PubMed Smith PA, Sakura H, Coles B, Gummerson N, Proks P, Ashcroft FM (1997) Electrogenic arginine transport mediates stimulus-secretion coupling in mouse pancreatic beta-cells. J Physiol 499:625–635PubMed
Metadata
Title
Insulin granule dynamics in pancreatic beta cells
Authors
Dr. P. Rorsman
E. Renström
Publication date
01-08-2003
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 8/2003
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-003-1153-1

Other articles of this Issue 8/2003

Diabetologia 8/2003 Go to the issue