Abstract
The fate of3H- and14C-labelled A-4166 was examined in rat pancreatic islets. The net uptake of the meglitinide analogue by islets incubated for 60 min in the presence of 0.1 mM A-4166 and then submitted to repeated washes was close to 0.1 pmol/islet. It was significantly increased when the concentration ofd-glucose in the incubation medium was raised from 2.8 to 16.7 mM. No sizeable internalization of tritiated A-4166 into insulin-producing cells could be detected by autoradiography. These findings suggest that the interaction of A-4166 with the beta-cell may be restricted to its insertion on the plasma membrane and binding to sulphonylurea receptors.
References
Malaisse WJ, Stimulation of insulin release by non-sulfonylurea hypoglycemic agents: the meglitinide family. Horm Metab Res 27:263–266, 1995
Malaisse WJ, Sato F, Insulinotropic action of sodium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate. I. Secretory and cationic aspects. Gen Pharmacol 26:1313–1318, 1995
Lins L, Brasseur R, Malaisse WJ, Conformational analysis of non-sulfonylurea hypoglycemic agents of the meglitinide family. Biochem Pharmacol 50:1879–1884, 1995
Bakkali Nadi A, Malaisse-Lagae F, Malaisse WJ, Insulinotropic action of meglitinide analogs: concentration-response relationship and nutrient dependency. Diabetes Res 27:81–87, 1994
Van Onderbergen A, Malaisse-Lagae F, Malaisse WJ, Effect of ATP and hypoglycaemic agents on45Ca uptake by subcellular fractions prepared from rat pancreatic islets. Med Sci Res 23:843–844, 1995
Viñambres C, Garcia-Martinez JA, Villanueva-Peñacarrillo ML, Valverde I, Malaisse WJ, Preservation of nutrient-stimulated biosynthetic activity in pancreatic islets exposed to a meglitinide analogue. Med Sci Res 23:779–780, 1995
Bakkali Nadi A, Zhang T-M, Malaisse WJ, Effects of the methyl esters of pyruvate, succinate and glutamate on the secretory response to meglitinide analogues in rat pancreatic islets. Pharmacol Res 33:191–194, 1996
Malaisse WJ, Insulinotropic action of meglitinide analogs: modulation by an activator of ATP-sensitive K+ channels and high extracellular K+ concentrations. Pharmacol Res 32:111–114, 1995
Malaisse-Lagae F, Malaisse WJ, Insulin release by pancreatic islets. In: Larner R, Pohl SL (eds) Methods in diabetes research. Wiley, New York, pp 147–152, 1984
Malaisse-Lagae F, Malaisse WJ, The stimulus-secretion coupling of glucose-induced insulin release. III. Uptake of45calcium by isolated islets of Langerhans. Endocrinology 88:72–89, 1971
Marynissen G, Smets G, Klöppel G, Gerlache L, Malaisse WJ, Internalization of glimepiride and glibenclamide in the pancreatic B-cell. Acta Diabetol 29:113–114, 1992
Sehlin J, Evidence for specific binding of tolbutamide to the plasma membrane of the pancreatic B-cells. Acta Diabetol Lat 10:1052–1060, 1973
Carpentier J-L, Sawano F, Ravazzola M, Malaisse WJ, Internalization of3H-glibenclamide in pancreatic islet cells. Diabetologia 29:259–261, 1986
Malaisse WJ, Lebrun P, Iterative stimulation of pancreatic islets by glipizide. Pharmacology 46:43–49, 1993
Lebrun P, Malaisse WJ, Herchuelz A, Modalities of gliclazide-induced Ca2+ influx into the pancreatic B-cell. Diabetes 31: 1010–1015, 1982
Lebrun P, Malaisse WJ, Cationic and secretory effects of glimepiride and glibenclamide in perifused rat islets. Pharmacol Toxicol 70:357–360, 1992
Malaisse WJ, Lebrun P, Sener A, Modulation of the insulinotropic action of glibenclamide and glimepiride by nutrient secretagogues in pancreatic islets from normoglycemic and hyperglycemic rats. Biochem Pharmacol 45:1845–1849, 1993
Täljedal I-B, Uptake of glibornuride by microdissected pancreatic islets. Horm Res 5:211–216, 1974
Deleers M, Ruysschaert J-M, Malaisse WJ, Glucose induces membrane changes detected by fluorescence polarization in endocrine pancreatic cells. Biochem Biophys Res Commun 98:255–260, 1981
Deleers M, Malaisse WJ, Binding of hypoglycaemic sulfonylureas to an artificial phospholipid bilayer. Diabetologia 26: 55–59, 1984
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Malaisse-Lagae, F., Malaisse, W.J. Fate of3H- and14C-labelled A-4166 in pancreatic islets. Acta Diabetol 33, 298–300 (1996). https://doi.org/10.1007/BF00571569
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DOI: https://doi.org/10.1007/BF00571569