Skip to main content
Top
Published in: BMC Immunology 1/2008

Open Access 01-12-2008 | Research article

Macropinocytosis is decreased in diabetic mouse macrophages and is regulated by AMPK

Authors: Christopher B Guest, Kenneth S Chakour, Gregory G Freund

Published in: BMC Immunology | Issue 1/2008

Login to get access

Abstract

Background

Macrophages (MΦs) utilize macropinocytosis to integrate immune and metabolic signals in order to initiate an effective immune response. Diabetes is characterized by metabolic abnormalities and altered immune function. Here we examine the influence of diabetes on macropinocytosis in primary mouse macrophages and in an in vitro diabetes model.

Results

The data demonstrate that peritoneal MΦs from diabetic (db/db) mice had reduced macropinocytosis when compared to MΦs from non-diabetic (db/+) mice. Additionally, MΦs cultured in hyperglycemic conditions were less adept at macropinocytosis than those cultured in low glucose. Notably, AMP-activated protein kinase (AMPK) activity was decreased in MΦs cultured in hyperglycemic conditions. Activation of AMPK with leptin or 5-aminoimidazole-4-carboxamide-1-β-riboside (AICAR) increased macropinocytosis and inhibition of AMPK with compound C decreased macropinocytosis.

Conclusion

Taken together, these findings indicate that MΦs from diabetic mice have decreased macropinocytosis. This decrease appears dependent on reduced AMPK activity. These results demonstrate a previously unrealized role for AMPK in MΦs and suggest that increasing AMPK activity in diabetic MΦs could improve innate immunity and decrease susceptibility to infection.
Appendix
Available only for authorised users
Literature
1.
go back to reference Gordon S, Taylor PR: Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005, 5 (12): 953-964. 10.1038/nri1733.CrossRefPubMed Gordon S, Taylor PR: Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005, 5 (12): 953-964. 10.1038/nri1733.CrossRefPubMed
2.
go back to reference Araki N, Johnson MT, Swanson JA: A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages. J Cell Biol. 1996, 135 (5): 1249-1260. 10.1083/jcb.135.5.1249.CrossRefPubMed Araki N, Johnson MT, Swanson JA: A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages. J Cell Biol. 1996, 135 (5): 1249-1260. 10.1083/jcb.135.5.1249.CrossRefPubMed
3.
go back to reference Swanson JA, Watts C: Macropinocytosis. Trends Cell Biol. 1995, 5 (11): 424-428. 10.1016/S0962-8924(00)89101-1.CrossRefPubMed Swanson JA, Watts C: Macropinocytosis. Trends Cell Biol. 1995, 5 (11): 424-428. 10.1016/S0962-8924(00)89101-1.CrossRefPubMed
4.
go back to reference Mattei F, Schiavoni G, Borghi P, Venditti M, Canini I, Sestili P, Pietraforte I, Morse HC, Ramoni C, Belardelli F, Gabriele L: ICSBP/IRF-8 differentially regulates antigen uptake during dendritic-cell development and affects antigen presentation to CD4+ T cells. Blood. 2006, 108 (2): 609-617. 10.1182/blood-2005-11-4490.CrossRefPubMed Mattei F, Schiavoni G, Borghi P, Venditti M, Canini I, Sestili P, Pietraforte I, Morse HC, Ramoni C, Belardelli F, Gabriele L: ICSBP/IRF-8 differentially regulates antigen uptake during dendritic-cell development and affects antigen presentation to CD4+ T cells. Blood. 2006, 108 (2): 609-617. 10.1182/blood-2005-11-4490.CrossRefPubMed
5.
go back to reference O'Connor JC, Satpathy A, Hartman ME, Horvath EM, Kelley KW, Dantzer R, Johnson RW, Freund GG: IL-1beta-mediated innate immunity is amplified in the db/db mouse model of type 2 diabetes. J Immunol. 2005, 174 (8): 4991-4997.CrossRefPubMed O'Connor JC, Satpathy A, Hartman ME, Horvath EM, Kelley KW, Dantzer R, Johnson RW, Freund GG: IL-1beta-mediated innate immunity is amplified in the db/db mouse model of type 2 diabetes. J Immunol. 2005, 174 (8): 4991-4997.CrossRefPubMed
6.
go back to reference Johnson DR, O'Connor JC, Dantzer R, Freund GG: Inhibition of vagally mediated immune-to-brain signaling by vanadyl sulfate speeds recovery from sickness. Proc Natl Acad Sci U S A. 2005, 102 (42): 15184-15189. 10.1073/pnas.0507191102.PubMedCentralCrossRefPubMed Johnson DR, O'Connor JC, Dantzer R, Freund GG: Inhibition of vagally mediated immune-to-brain signaling by vanadyl sulfate speeds recovery from sickness. Proc Natl Acad Sci U S A. 2005, 102 (42): 15184-15189. 10.1073/pnas.0507191102.PubMedCentralCrossRefPubMed
7.
go back to reference Sherry CL, O'Connor JC, Kramer JM, Freund GG: Augmented lipopolysaccharide-induced TNF-alpha production by peritoneal macrophages in type 2 diabetic mice is dependent on elevated glucose and requires p38 MAPK. J Immunol. 2007, 178 (2): 663-670.CrossRefPubMed Sherry CL, O'Connor JC, Kramer JM, Freund GG: Augmented lipopolysaccharide-induced TNF-alpha production by peritoneal macrophages in type 2 diabetic mice is dependent on elevated glucose and requires p38 MAPK. J Immunol. 2007, 178 (2): 663-670.CrossRefPubMed
8.
go back to reference Joshi N, Caputo GM, Weitekamp MR, Karchmer AW: Infections in patients with diabetes mellitus. N Engl J Med. 1999, 341 (25): 1906-1912. 10.1056/NEJM199912163412507.CrossRefPubMed Joshi N, Caputo GM, Weitekamp MR, Karchmer AW: Infections in patients with diabetes mellitus. N Engl J Med. 1999, 341 (25): 1906-1912. 10.1056/NEJM199912163412507.CrossRefPubMed
9.
go back to reference Zhang F, Basinski MB, Beals JM, Briggs SL, Churgay LM, Clawson DK, DiMarchi RD, Furman TC, Hale JE, Hsiung HM, Schoner BE, Smith DP, Zhang XY, Wery JP, Schevitz RW: Crystal structure of the obese protein leptin-E100. Nature. 1997, 387 (6629): 206-209. 10.1038/387206a0.CrossRefPubMed Zhang F, Basinski MB, Beals JM, Briggs SL, Churgay LM, Clawson DK, DiMarchi RD, Furman TC, Hale JE, Hsiung HM, Schoner BE, Smith DP, Zhang XY, Wery JP, Schevitz RW: Crystal structure of the obese protein leptin-E100. Nature. 1997, 387 (6629): 206-209. 10.1038/387206a0.CrossRefPubMed
10.
go back to reference Friedman JM, Halaas JL: Leptin and the regulation of body weight in mammals. Nature. 1998, 395 (6704): 763-770. 10.1038/27376.CrossRefPubMed Friedman JM, Halaas JL: Leptin and the regulation of body weight in mammals. Nature. 1998, 395 (6704): 763-770. 10.1038/27376.CrossRefPubMed
11.
go back to reference Goren I, Kampfer H, Podda M, Pfeilschifter J, Frank S: Leptin and wound inflammation in diabetic ob/ob mice: differential regulation of neutrophil and macrophage influx and a potential role for the scab as a sink for inflammatory cells and mediators. Diabetes. 2003, 52 (11): 2821-2832. 10.2337/diabetes.52.11.2821.CrossRefPubMed Goren I, Kampfer H, Podda M, Pfeilschifter J, Frank S: Leptin and wound inflammation in diabetic ob/ob mice: differential regulation of neutrophil and macrophage influx and a potential role for the scab as a sink for inflammatory cells and mediators. Diabetes. 2003, 52 (11): 2821-2832. 10.2337/diabetes.52.11.2821.CrossRefPubMed
12.
go back to reference Kampfer H, Schmidt R, Geisslinger G, Pfeilschifter J, Frank S: Wound inflammation in diabetic ob/ob mice: functional coupling of prostaglandin biosynthesis to cyclooxygenase-1 activity in diabetes-impaired wound healing. Diabetes. 2005, 54 (5): 1543-1551. 10.2337/diabetes.54.5.1543.CrossRefPubMed Kampfer H, Schmidt R, Geisslinger G, Pfeilschifter J, Frank S: Wound inflammation in diabetic ob/ob mice: functional coupling of prostaglandin biosynthesis to cyclooxygenase-1 activity in diabetes-impaired wound healing. Diabetes. 2005, 54 (5): 1543-1551. 10.2337/diabetes.54.5.1543.CrossRefPubMed
13.
go back to reference Guest CB, Hartman ME, O'Connor JC, Chakour KS, Sovari AA, Freund GG: Phagocytosis of cholesteryl ester is amplified in diabetic mouse macrophages and is largely mediated by CD36 and SR-A. PLoS ONE. 2007, 2: e511-10.1371/journal.pone.0000511.PubMedCentralCrossRefPubMed Guest CB, Hartman ME, O'Connor JC, Chakour KS, Sovari AA, Freund GG: Phagocytosis of cholesteryl ester is amplified in diabetic mouse macrophages and is largely mediated by CD36 and SR-A. PLoS ONE. 2007, 2: e511-10.1371/journal.pone.0000511.PubMedCentralCrossRefPubMed
14.
go back to reference Mancuso P, Gottschalk A, Phare SM, Peters-Golden M, Lukacs NW, Huffnagle GB: Leptin-deficient mice exhibit impaired host defense in Gram-negative pneumonia. J Immunol. 2002, 168 (8): 4018-4024.CrossRefPubMed Mancuso P, Gottschalk A, Phare SM, Peters-Golden M, Lukacs NW, Huffnagle GB: Leptin-deficient mice exhibit impaired host defense in Gram-negative pneumonia. J Immunol. 2002, 168 (8): 4018-4024.CrossRefPubMed
15.
go back to reference Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Carling D, Kahn BB: Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature. 2002, 415 (6869): 339-343. 10.1038/415339a.CrossRefPubMed Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Carling D, Kahn BB: Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature. 2002, 415 (6869): 339-343. 10.1038/415339a.CrossRefPubMed
16.
go back to reference Uotani S, Abe T, Yamaguchi Y: Leptin activates AMP-activated protein kinase in hepatic cells via a JAK2-dependent pathway. Biochem Biophys Res Commun. 2006, 351 (1): 171-175. 10.1016/j.bbrc.2006.10.015.CrossRefPubMed Uotani S, Abe T, Yamaguchi Y: Leptin activates AMP-activated protein kinase in hepatic cells via a JAK2-dependent pathway. Biochem Biophys Res Commun. 2006, 351 (1): 171-175. 10.1016/j.bbrc.2006.10.015.CrossRefPubMed
17.
go back to reference Neumeier M, Weigert J, Schaffler A, Wehrwein G, Muller-Ladner U, Scholmerich J, Wrede C, Buechler C: Different effects of adiponectin isoforms in human monocytic cells. J Leukoc Biol. 2006, 79 (4): 803-808. 10.1189/jlb.0905521.CrossRefPubMed Neumeier M, Weigert J, Schaffler A, Wehrwein G, Muller-Ladner U, Scholmerich J, Wrede C, Buechler C: Different effects of adiponectin isoforms in human monocytic cells. J Leukoc Biol. 2006, 79 (4): 803-808. 10.1189/jlb.0905521.CrossRefPubMed
18.
go back to reference Giri S, Rattan R, Haq E, Khan M, Yasmin R, Won JS, Key L, Singh AK, Singh I: AICAR inhibits adipocyte differentiation in 3T3L1 and restores metabolic alterations in diet-induced obesity mice model. Nutr Metab (Lond). 2006, 3: 31-10.1186/1743-7075-3-31.CrossRef Giri S, Rattan R, Haq E, Khan M, Yasmin R, Won JS, Key L, Singh AK, Singh I: AICAR inhibits adipocyte differentiation in 3T3L1 and restores metabolic alterations in diet-induced obesity mice model. Nutr Metab (Lond). 2006, 3: 31-10.1186/1743-7075-3-31.CrossRef
19.
go back to reference Kanellis J, Kandane RK, Etemadmoghadam D, Fraser SA, Mount PF, Levidiotis V, Kemp BE, Power DA: Activators of the energy sensing kinase AMPK inhibit random cell movement and chemotaxis in U937 cells. Immunol Cell Biol. 2006, 84 (1): 6-12. 10.1111/j.1440-1711.2005.01388.x.CrossRefPubMed Kanellis J, Kandane RK, Etemadmoghadam D, Fraser SA, Mount PF, Levidiotis V, Kemp BE, Power DA: Activators of the energy sensing kinase AMPK inhibit random cell movement and chemotaxis in U937 cells. Immunol Cell Biol. 2006, 84 (1): 6-12. 10.1111/j.1440-1711.2005.01388.x.CrossRefPubMed
20.
go back to reference Burcelin R, Crivelli V, Perrin C, Da Costa A, Mu J, Kahn BB, Birnbaum MJ, Kahn CR, Vollenweider P, Thorens B: GLUT4, AMP kinase, but not the insulin receptor, are required for hepatoportal glucose sensor-stimulated muscle glucose utilization. J Clin Invest. 2003, 111 (10): 1555-1562.PubMedCentralCrossRefPubMed Burcelin R, Crivelli V, Perrin C, Da Costa A, Mu J, Kahn BB, Birnbaum MJ, Kahn CR, Vollenweider P, Thorens B: GLUT4, AMP kinase, but not the insulin receptor, are required for hepatoportal glucose sensor-stimulated muscle glucose utilization. J Clin Invest. 2003, 111 (10): 1555-1562.PubMedCentralCrossRefPubMed
21.
go back to reference Ma HT, Lin WW, Zhao B, Wu WT, Huang W, Li Y, Jones NL, Kruth HS: Protein kinase C beta and delta isoenzymes mediate cholesterol accumulation in PMA-activated macrophages. Biochem Biophys Res Commun. 2006, 349 (1): 214-220. 10.1016/j.bbrc.2006.08.018.CrossRefPubMed Ma HT, Lin WW, Zhao B, Wu WT, Huang W, Li Y, Jones NL, Kruth HS: Protein kinase C beta and delta isoenzymes mediate cholesterol accumulation in PMA-activated macrophages. Biochem Biophys Res Commun. 2006, 349 (1): 214-220. 10.1016/j.bbrc.2006.08.018.CrossRefPubMed
22.
go back to reference Wipf P, Halter RJ: Chemistry and biology of wortmannin. Org Biomol Chem. 2005, 3 (11): 2053-2061. 10.1039/b504418a.CrossRefPubMed Wipf P, Halter RJ: Chemistry and biology of wortmannin. Org Biomol Chem. 2005, 3 (11): 2053-2061. 10.1039/b504418a.CrossRefPubMed
23.
go back to reference Hartman ME, O'Connor JC, Godbout JP, Minor KD, Mazzocco VR, Freund GG: Insulin receptor substrate-2-dependent interleukin-4 signaling in macrophages is impaired in two models of type 2 diabetes mellitus. J Biol Chem. 2004, 279 (27): 28045-50. Epub 2004 Apr 27.. 10.1074/jbc.M404368200.CrossRefPubMed Hartman ME, O'Connor JC, Godbout JP, Minor KD, Mazzocco VR, Freund GG: Insulin receptor substrate-2-dependent interleukin-4 signaling in macrophages is impaired in two models of type 2 diabetes mellitus. J Biol Chem. 2004, 279 (27): 28045-50. Epub 2004 Apr 27.. 10.1074/jbc.M404368200.CrossRefPubMed
24.
go back to reference Deszo EL, Brake DK, Cengel KA, Kelley KW, Freund GG: CD45 negatively regulates monocytic cell differentiation by inhibiting phorbol 12-myristate 13-acetate-dependent activation and tyrosine phosphorylation of protein kinase Cdelta. J Biol Chem. 2001, 276 (13): 10212-10217. 10.1074/jbc.M010589200.CrossRefPubMed Deszo EL, Brake DK, Cengel KA, Kelley KW, Freund GG: CD45 negatively regulates monocytic cell differentiation by inhibiting phorbol 12-myristate 13-acetate-dependent activation and tyrosine phosphorylation of protein kinase Cdelta. J Biol Chem. 2001, 276 (13): 10212-10217. 10.1074/jbc.M010589200.CrossRefPubMed
25.
go back to reference Kahn BB, Alquier T, Carling D, Hardie DG: AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005, 1 (1): 15-25. 10.1016/j.cmet.2004.12.003.CrossRefPubMed Kahn BB, Alquier T, Carling D, Hardie DG: AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005, 1 (1): 15-25. 10.1016/j.cmet.2004.12.003.CrossRefPubMed
26.
go back to reference Kramer DK, Al-Khalili L, Guigas B, Leng Y, Garcia-Roves PM, Krook A: Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle. J Biol Chem. 2007, 282 (27): 19313-19320. 10.1074/jbc.M702329200.CrossRefPubMed Kramer DK, Al-Khalili L, Guigas B, Leng Y, Garcia-Roves PM, Krook A: Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle. J Biol Chem. 2007, 282 (27): 19313-19320. 10.1074/jbc.M702329200.CrossRefPubMed
27.
go back to reference Guigas B, Bertrand L, Taleux N, Foretz M, Wiernsperger N, Vertommen D, Andreelli F, Viollet B, Hue L: 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation. Diabetes. 2006, 55 (4): 865-874. 10.2337/diabetes.55.04.06.db05-1178.CrossRefPubMed Guigas B, Bertrand L, Taleux N, Foretz M, Wiernsperger N, Vertommen D, Andreelli F, Viollet B, Hue L: 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation. Diabetes. 2006, 55 (4): 865-874. 10.2337/diabetes.55.04.06.db05-1178.CrossRefPubMed
28.
go back to reference Bertrand L, Ginion A, Beauloye C, Hebert AD, Guigas B, Hue L, Vanoverschelde JL: AMPK activation restores the stimulation of glucose uptake in an in vitro model of insulin-resistant cardiomyocytes via the activation of protein kinase B. Am J Physiol Heart Circ Physiol. 2006, 291 (1): H239-50. 10.1152/ajpheart.01269.2005.CrossRefPubMed Bertrand L, Ginion A, Beauloye C, Hebert AD, Guigas B, Hue L, Vanoverschelde JL: AMPK activation restores the stimulation of glucose uptake in an in vitro model of insulin-resistant cardiomyocytes via the activation of protein kinase B. Am J Physiol Heart Circ Physiol. 2006, 291 (1): H239-50. 10.1152/ajpheart.01269.2005.CrossRefPubMed
29.
go back to reference Steinberg GR: Inflammation in obesity is the common link between defects in fatty acid metabolism and insulin resistance. Cell Cycle. 2007, 6 (8): 888-894.CrossRefPubMed Steinberg GR: Inflammation in obesity is the common link between defects in fatty acid metabolism and insulin resistance. Cell Cycle. 2007, 6 (8): 888-894.CrossRefPubMed
30.
go back to reference Stroschein-Stevenson SL, Foley E, O'Farrell PH, Johnson AD: Identification of Drosophila gene products required for phagocytosis of Candida albicans. PLoS Biol. 2006, 4 (1): e4-10.1371/journal.pbio.0040004.PubMedCentralCrossRefPubMed Stroschein-Stevenson SL, Foley E, O'Farrell PH, Johnson AD: Identification of Drosophila gene products required for phagocytosis of Candida albicans. PLoS Biol. 2006, 4 (1): e4-10.1371/journal.pbio.0040004.PubMedCentralCrossRefPubMed
31.
go back to reference Stein SC, Woods A, Jones NA, Davison MD, Carling D: The regulation of AMP-activated protein kinase by phosphorylation. Biochem J. 2000, 345 Pt 3: 437-443. 10.1042/0264-6021:3450437.CrossRefPubMed Stein SC, Woods A, Jones NA, Davison MD, Carling D: The regulation of AMP-activated protein kinase by phosphorylation. Biochem J. 2000, 345 Pt 3: 437-443. 10.1042/0264-6021:3450437.CrossRefPubMed
32.
go back to reference Laderoute KR, Amin K, Calaoagan JM, Knapp M, Le T, Orduna J, Foretz M, Viollet B: 5'-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments. Mol Cell Biol. 2006, 26 (14): 5336-5347. 10.1128/MCB.00166-06.PubMedCentralCrossRefPubMed Laderoute KR, Amin K, Calaoagan JM, Knapp M, Le T, Orduna J, Foretz M, Viollet B: 5'-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments. Mol Cell Biol. 2006, 26 (14): 5336-5347. 10.1128/MCB.00166-06.PubMedCentralCrossRefPubMed
33.
go back to reference Halse R, Fryer LG, McCormack JG, Carling D, Yeaman SJ: Regulation of glycogen synthase by glucose and glycogen: a possible role for AMP-activated protein kinase. Diabetes. 2003, 52 (1): 9-15. 10.2337/diabetes.52.1.9.CrossRefPubMed Halse R, Fryer LG, McCormack JG, Carling D, Yeaman SJ: Regulation of glycogen synthase by glucose and glycogen: a possible role for AMP-activated protein kinase. Diabetes. 2003, 52 (1): 9-15. 10.2337/diabetes.52.1.9.CrossRefPubMed
34.
go back to reference Ruderman NB, Keller C, Richard AM, Saha AK, Luo Z, Xiang X, Giralt M, Ritov VB, Menshikova EV, Kelley DE, Hidalgo J, Pedersen BK, Kelly M: Interleukin-6 regulation of AMP-activated protein kinase. Potential role in the systemic response to exercise and prevention of the metabolic syndrome. Diabetes. 2006, 55 Suppl 2: S48-54. 10.2337/db06-S007.CrossRefPubMed Ruderman NB, Keller C, Richard AM, Saha AK, Luo Z, Xiang X, Giralt M, Ritov VB, Menshikova EV, Kelley DE, Hidalgo J, Pedersen BK, Kelly M: Interleukin-6 regulation of AMP-activated protein kinase. Potential role in the systemic response to exercise and prevention of the metabolic syndrome. Diabetes. 2006, 55 Suppl 2: S48-54. 10.2337/db06-S007.CrossRefPubMed
35.
go back to reference Kim JH, Kim JE, Liu HY, Cao W, Chen J: Regulation of IL-6 induced hepatic insulin resistance by mtor through the STAT3-SOCS3 pathway. J Biol Chem. 2007 Kim JH, Kim JE, Liu HY, Cao W, Chen J: Regulation of IL-6 induced hepatic insulin resistance by mtor through the STAT3-SOCS3 pathway. J Biol Chem. 2007
36.
go back to reference O'Connor JC, Sherry CL, Guest CB, Freund GG: Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. J Immunol. 2007, 178 (11): 6886-6893.CrossRefPubMed O'Connor JC, Sherry CL, Guest CB, Freund GG: Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3. J Immunol. 2007, 178 (11): 6886-6893.CrossRefPubMed
37.
go back to reference Steinberg GR, McAinch AJ, Chen MB, O'Brien PE, Dixon JB, Cameron-Smith D, Kemp BE: The suppressor of cytokine signaling 3 inhibits leptin activation of AMP-kinase in cultured skeletal muscle of obese humans. J Clin Endocrinol Metab. 2006, 91 (9): 3592-3597. 10.1210/jc.2006-0638.CrossRefPubMed Steinberg GR, McAinch AJ, Chen MB, O'Brien PE, Dixon JB, Cameron-Smith D, Kemp BE: The suppressor of cytokine signaling 3 inhibits leptin activation of AMP-kinase in cultured skeletal muscle of obese humans. J Clin Endocrinol Metab. 2006, 91 (9): 3592-3597. 10.1210/jc.2006-0638.CrossRefPubMed
38.
go back to reference Shaw RJ, Kosmatka M, Bardeesy N, Hurley RL, Witters LA, DePinho RA, Cantley LC: The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci U S A. 2004, 101 (10): 3329-3335. 10.1073/pnas.0308061100.PubMedCentralCrossRefPubMed Shaw RJ, Kosmatka M, Bardeesy N, Hurley RL, Witters LA, DePinho RA, Cantley LC: The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci U S A. 2004, 101 (10): 3329-3335. 10.1073/pnas.0308061100.PubMedCentralCrossRefPubMed
39.
go back to reference Hurley RL, Anderson KA, Franzone JM, Kemp BE, Means AR, Witters LA: The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J Biol Chem. 2005, 280 (32): 29060-29066. 10.1074/jbc.M503824200.CrossRefPubMed Hurley RL, Anderson KA, Franzone JM, Kemp BE, Means AR, Witters LA: The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J Biol Chem. 2005, 280 (32): 29060-29066. 10.1074/jbc.M503824200.CrossRefPubMed
40.
go back to reference An Z, Wang H, Song P, Zhang M, Gong X, Zou MH: Nicotine-induced activation of AMP-activated protein kinase Inhibits fatty acid synthase in 3T3-L1 adipocytes: A role for oxidant stress. J Biol Chem. 2007 An Z, Wang H, Song P, Zhang M, Gong X, Zou MH: Nicotine-induced activation of AMP-activated protein kinase Inhibits fatty acid synthase in 3T3-L1 adipocytes: A role for oxidant stress. J Biol Chem. 2007
41.
go back to reference Meley D, Bauvy C, Houben-Weerts JH, Dubbelhuis PF, Helmond MT, Codogno P, Meijer AJ: AMP-activated protein kinase and the regulation of autophagic proteolysis. J Biol Chem. 2006, 281 (46): 34870-34879. 10.1074/jbc.M605488200.CrossRefPubMed Meley D, Bauvy C, Houben-Weerts JH, Dubbelhuis PF, Helmond MT, Codogno P, Meijer AJ: AMP-activated protein kinase and the regulation of autophagic proteolysis. J Biol Chem. 2006, 281 (46): 34870-34879. 10.1074/jbc.M605488200.CrossRefPubMed
42.
go back to reference Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Eagle AR, Vats D, Brombacher F, Ferrante AW, Chawla A: Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature. 2007, 447 (7148): 1116-1120. 10.1038/nature05894.PubMedCentralCrossRefPubMed Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Eagle AR, Vats D, Brombacher F, Ferrante AW, Chawla A: Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature. 2007, 447 (7148): 1116-1120. 10.1038/nature05894.PubMedCentralCrossRefPubMed
43.
go back to reference Hackstein H, Taner T, Logar AJ, Thomson AW: Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells. Blood. 2002, 100 (3): 1084-1087. 10.1182/blood.V100.3.1084.CrossRefPubMed Hackstein H, Taner T, Logar AJ, Thomson AW: Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells. Blood. 2002, 100 (3): 1084-1087. 10.1182/blood.V100.3.1084.CrossRefPubMed
44.
go back to reference Hackstein H, Morelli AE, Larregina AT, Ganster RW, Papworth GD, Logar AJ, Watkins SC, Falo LD, Thomson AW: Aspirin inhibits in vitro maturation and in vivo immunostimulatory function of murine myeloid dendritic cells. J Immunol. 2001, 166 (12): 7053-7062.CrossRefPubMed Hackstein H, Morelli AE, Larregina AT, Ganster RW, Papworth GD, Logar AJ, Watkins SC, Falo LD, Thomson AW: Aspirin inhibits in vitro maturation and in vivo immunostimulatory function of murine myeloid dendritic cells. J Immunol. 2001, 166 (12): 7053-7062.CrossRefPubMed
Metadata
Title
Macropinocytosis is decreased in diabetic mouse macrophages and is regulated by AMPK
Authors
Christopher B Guest
Kenneth S Chakour
Gregory G Freund
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2008
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/1471-2172-9-42

Other articles of this Issue 1/2008

BMC Immunology 1/2008 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine