Skip to main content

Assays for the Expression and Release of Insulin and Glucose-Regulating Peptide Hormones from Pancreatic β-Cell

  • Living reference work entry
  • First Online:
Drug Discovery and Evaluation: Pharmacological Assays
  • 660 Accesses

Abstract

The in vitro perfusion of the isolated rat pancreas as described by Anderson and Long (1947), Ross (1972), Grodsky and coworkers (1983, 1984), and Muñoz and coworkers (1995) offers the advantage to study the influence of carbohydrates, hormones, and drugs such as sulfonylureas not only on insulin but also on glucagon and somatostatin secretion without interference of secondary effects resulting from changes in hepatic, pituitary, or adrenal functions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References and Further Reading

Insulin Release from the Isolated Perfused Rat Pancreas; Insulin Release from the Isolated Perifused Rat Pancreatic Islets

  • Anderson E, Long JA (1947) The effect of hyperglycemia on insulin secretion as determined with the isolated rat pancreas in a perfusion apparatus. Endocrinology 40:92–97

    CAS  PubMed  Google Scholar 

  • Fletcher DJ, Weir G (1984) Tissue culture of dispersed islet cells. In: Larner J, Pohl SL (eds) Methods in diabetes research, vol I, Laboratory methods, Part A. Wiley, New York, pp 167–173

    Google Scholar 

  • Geisen K (1988) Special pharmacology of the new sulfonylurea glimepiride. Arzneim Forsch/Drug Res 38:1120–1130

    CAS  Google Scholar 

  • Grodsky GM, Heldt A (1984) Method for the in vitro perfusion of the pancreas. In: Larner J, Pohl SL (eds) Methods in diabetes research, vol I, Laboratory methods, Part B. Wiley, New York, pp 137–146

    Google Scholar 

  • Grodsky GM, Batts AA, Bennett LL, Vicella C, McWilliams NB, Smith DF (1983) Effects of carbohydrates on secretion of insulin from isolated rat pancreas. Am J Physiol 205:638–644

    Google Scholar 

  • Horaguchi A, Merrell RC (1981) Preparation of viable islet cells from dogs by a new method. Diabetes 30:455–458

    CAS  PubMed  Google Scholar 

  • Idahl L (1972) A microperifusion device for pancreatic islets allowing concomitant recordings of intermediate metabolites and insulin release. Anal Biochem 50:386–398

    CAS  PubMed  Google Scholar 

  • Kaiser N, Cerasi E (1991) Long term monolayer culture of adult rat islet of Langerhans. An experimental model for studying chronic modulation of β-cell function. In: Greenstein B (ed) Neuroendocrine research methods, vol 1. Harwood Academic, Springfield, Massachussetts, pp 131–147. Chapter 6

    Google Scholar 

  • Lernmark Å (1974) The preparation of, and studies on, free cell suspensions from mouse pancreatic islets. Diabetologia 10:431–438

    CAS  PubMed  Google Scholar 

  • Malaisse-Lagae F, Malaisse WJ (1984) Insulin release by pancreatic islets. In: Larner J, Pohl SL (eds) Methods in diabetes research, vol I, Laboratory methods, Part B. Wiley, New York, pp 147–152

    Google Scholar 

  • Marchetti P, Giannarelli R, di Carlo A, Zappella A, Masoni A, Masiello P, Marchetti A, Picaro L, Navalesi R (1989) In vitro function of porcine islets of Langerhans. Diabet Nutr Metab Clin Exp 2:105–109

    Google Scholar 

  • McDaniel ML, Colca JR, Kotagal N (1984) Islet cell membrane isolation and characterization. In: Larner J, Pohl SL (eds) Methods in diabetes research, vol I, Laboratory methods, Part A. Wiley, New York, pp 153–166

    Google Scholar 

  • Muñoz M, Sweiry JH, Mann GE (1995) Insulin stimulates cationic amino acid transport in the isolated perfused rat pancreas. Exp Physiol 80:745–753

    PubMed  Google Scholar 

  • Panten U, Ishida H, Schauder P, Frerichs H, Hasselblatt A (1977) A versatile microperifusion system. Anal Biochem 82:317–326

    CAS  PubMed  Google Scholar 

  • Pipeleers DG (1984) Islet cell purification. In: Larner J, Pohl SL (eds) Methods in diabetes research, vol I, Laboratory methods, Part B. Wiley, New York, pp 185–211

    Google Scholar 

  • Ross BD (1972) Endocrine organs: pancreas. In: Ross BD (ed) Perfusion techniques in biochemistry. A laboratory manual in the use of isolated perfused organs in biochemical experimentation. Clarendon Press, Oxford, pp 321–355

    Google Scholar 

  • Schatz H, Maier V, Hinz M, Nierle C, Pfeiffer EF (1972) The effect of tolbutamide and glibenclamide on the incorporation of [3H] leucine and on the conversion of proinsulin to insulin in isolated pancreatic islets. FEBS Lett 26:237–240

    CAS  PubMed  Google Scholar 

Insulin Release from Cultured β-Cells; Lipolysis in β-Cell

  • Lindvall H, Nevsten P, Strom K, Wallenberg R, Sundler F, Langin D, Sorhede-Winzell M, Holm C (2004) A novel hormone-sensitive lipase isoform expressed in pancreatic β-cells. J Biol Chem 279:3828–3836

    CAS  PubMed  Google Scholar 

  • Listenberger LL, Han X, Lewis SE, Cases S, Farese RV, Ory DS, Schaffer JE (2003) Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci U S A 100:3077–3082

    CAS  PubMed Central  PubMed  Google Scholar 

  • Merglen A, Theander S, Rubi B, Chaffard G, Wollheim CB, Maechler P (2004) Glucose sensitivity and metabolism-secretion coupling studied during two-year continuous culture in INS-1E insulinoma cells. Endocrinology 145:667–678

    CAS  PubMed  Google Scholar 

  • Mulder H, Holst LS, Svensson H, Degerman E, Sundler F, Ahren B, Rorsman P, Holm C (1999) Hormone-sensitive lipase, the rate-lmiting enzyme in triglyceride hydrolysis is expressed and active in β-cells. Diabetes 48:228–232

    Google Scholar 

  • Mulder H, Sorhede-Winzell M, Contreras JA, Fex M, Strom K, Ploug T, Galbo H, Arner P, Lundberg C, Sundler F (2003) Hormone-sensitive lipase null mice exhibits signs of impaired insulin sensitivity whereas insulin secretion is intact. J Biol Chem 278:36380–36388

    CAS  PubMed  Google Scholar 

  • Roduit R, Masiello P, Wang SP, Li H, Mitchell GA, Prentki M (2001) A role for hormone-sensitive lipase in glucose-stimulated insulin secretion. A study in hormone-sensitive lipase-deficient mice. Diabetes 50:1970–1975

    Google Scholar 

  • Sorhede-Winzell M, Svensson H, Arner P, Ahren B, Holm C (2001) The expression of hormone-sensitive lipase in clonal β-cells and rat islets is induced by long-term exposure to high glucose. Diabetes 50:2225–2230

    CAS  Google Scholar 

  • Sorhede-Winzell M, Holm C, Ahren B (2003a) Downregulation of islet hormone-sensitive lipase during long-term high-fat feeding. Biochem Biophys Res Commun 304:273–278

    CAS  Google Scholar 

  • Sorhede-Winzell M, Svensson H, Enerback S, Ravnskjaer K, Mandrup S, Esser V, Arner P, Alves-Guerra M-C, Miroux B, Sandler F (2003b) Pancreatic β-cell lipotoxicity induced by overexpression of hormone-sensitive lipase. Diabetes 52:2057–2065

    Google Scholar 

  • Yaney GC, Korchak HM, Corkey BE (2000) Long-chain acyl-CoA regulation of protein kinase C and fatty acid potentiation of glucose-stimulated insulin secretion in clonal beta-cells. Endocrinology 141:1989–1998

    CAS  PubMed  Google Scholar 

  • Yeaman SJ (2004) Hormone-sensitive lipase-new roles for an old enzyme. Biochem J 379:11–22

    CAS  PubMed Central  PubMed  Google Scholar 

Measurement of Ca2+ Levels; Measurement of 86Rb+ Efflux

  • Boyd III AE, Aguilar-Bryan L, Bryan J, Kunze DL, Moss L, Nelson DA, Rajan AS, Raef H, Xiang H, Yaney GC (1991) Sulfonylurea signal transduction. Recent Prog Horm Res 47:299–317

    Google Scholar 

  • Daniel S, Malkowitz L, Wang HC, Beer B, Blume AJ, Ziai MR (1991) Screening for potassium channel modulators by a high through-put 86-Rubidium efflux assay in a 96-well microtiter plate. J Pharmacol Methods 25:185–193

    CAS  PubMed  Google Scholar 

  • Freeman H, Shimomura K, Horner E, Cox RD, Ashcroft FM (2006) Nicotinamide nucleotide transhydrogenase: a key role in insulin secretion. Cell Metab 3:35–45

    CAS  PubMed  Google Scholar 

  • Hu W, Toral J, Cernovi P, Ziai R, Sokol PT (1995) Depolarization-induced 86Rb+ efflux in CHO cells expressing a recombinant potassium channel. J Pharmacol Toxicol Methods 34:1–7

    CAS  PubMed  Google Scholar 

  • Nelson TY, Gaines KL, Rajan AS, Berg M, Boyd AE III (1987) Increased cytosolic calcium. A signal for sulfonylurea-stimulated insulin release from beta cells. J Biol Chem 262:2606–2612

    Google Scholar 

  • Nichols CG et al (1996) Adenosine diphosphate as an intracellular regulator of insulin secretion. Science 272:1785–1887

    CAS  PubMed  Google Scholar 

  • Niki I, Kelly RP, Ashcroft SJH, Ashcroft FM (1989) ATP-sensitive K-channels in HIT T15 β-cells studied by patchclamp methods, 86Rb efflux and glibenclamide binding. Pflügers Arch 415:47–55

    Google Scholar 

  • Rorsman P, Trube G (1986) Calcium and delayed potassium currents in mouse pancreatic β-cells under voltage-clamp conditions. J Physiol 374:531–550

    CAS  PubMed Central  PubMed  Google Scholar 

  • Toye AA, Lippiat JD, Proks P, Shimomura K, Bentley L, Hugill A, Mijat V, Goldsworthy M, Moir L, Haynes A, Quarterman J, Freeman HC, Ashcroft FM, Cox RD (2005) A genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice. Diabetologia 48:675–686

    CAS  PubMed  Google Scholar 

Measurement of Cell Membrane Potential; Measurement of Cytosolic ATP Levels; Analysis of Lipotoxicity

  • Ashcroft FM (2005) ATP-sensitive potassium channelopathies: focus on insulin secretion. J Clin Invest 115:2047–2058

    Google Scholar 

  • Ashcroft FM, Rorsman P (1989) Electrophysiology of the pancreatic β-cell. Prog Biophys Mol Biol 54:87–143

    CAS  PubMed  Google Scholar 

  • Bryan J, Aguilar-Bryan (1997) The ABCs of ATP-sensitive potassium channels. Curr Opin Cell Biol 9:553–559

    Google Scholar 

  • Burdge GC, Wright P, Jones AE, Wooton SA (2000) A method for separation of phosphatidylcholine, triacylglycerol, nonesterified fatty acids and cholesterol esters from plasma by solid-phase extraction. Br J Nutr 84:781–787

    CAS  PubMed  Google Scholar 

  • Carpentier A, Giacca A, Lewis GF (2001) Effect of increased plasma non-esterified fatty acids (NEFA) on arginine-stimulated insulin secretion in obese humans. Diabetologia 44:1989–1997

    CAS  PubMed  Google Scholar 

  • Chutkow WA, Simon MC, Beau MML, Burant CF (1996) Cloning, tissue expression, and chromosomal localization of SUR2, the putative drug-binding subunit of cardiac, skeletal muscle and vascular KATP channels. Diabetes 45:1439–1445

    Google Scholar 

  • Cnop M, Hannaert JC, Hoorens A, Eizirik DL, Pipeleers DG (2001) Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation. Diabetes 50:1771–1777

    CAS  PubMed  Google Scholar 

  • Daut J, Klieber HG, Cyrys S, Noak T (1994) KATP channels and basal coronary vascular tone. Cardiovasc Res 28:811–817

    CAS  PubMed  Google Scholar 

  • Dobbins RL, Szczepaniak LS, Myhill J (2002) The composition of dietary fat directly influences glucose-stimulated insulin secretion in rats. Diabetes 51:1825–1833

    CAS  PubMed  Google Scholar 

  • Dunne MJ, Cosgrove KE, Shepherd RM, Aynsley-Green A, Lindley KJ (2004) Hyperinsulinemia in infancy: from basic science to clinical disease. Physiol Rev 84:239–275

    CAS  PubMed  Google Scholar 

  • El-Assaad W, Buteau J, Peyot ML (2003) Saturated fatty acids synergize with elevated glucose to cause pancreatic betacell death. Endocrinology 144:4154–4163

    CAS  PubMed  Google Scholar 

  • Fex M, Olofsson CS, Fransson U, Bacos K, Lindvall H, Sörhede-Winzell M, Rorsman P, Holm C, Mulder H (2004) Hormone-sensitive lipase deficiency in mouse islets abolishes neutral cholesterol ester hydrolase activity but leaves lipolysis, acylglycerides, fat oxidation, and insulin secretion intact. Endocrinology 145:3746–3753

    CAS  PubMed  Google Scholar 

  • Ford ES, Giles WH, Dietz WH (2002) Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 287:356–359

    PubMed  Google Scholar 

  • Gloyn AL et al (2004) Activating mutations in the ATP-sensitive potassium channel subunit Kir6.2 gene are associated with permanent neonatal diabetes. N Engl J Med 350:1838–1849

    CAS  PubMed  Google Scholar 

  • Gögelein H, Hartung J, Englert HC, Schölkens BA (1998) HMR 1883, a novel cardioselective inhibitor of the ATP-sensitive potassium channel. Part I. Effects on cardiomyocytes, coronary flow and pancreatic β-cells. J Pharmacol Exp Ther 286:1453–1464

    PubMed  Google Scholar 

  • Gomora JC, Enyeart JJ (1999) Dual pharmacological properties of a cyclic AMP-sensitive potassium channel. J Pharmacol Exp Ther 290:266–275

    CAS  PubMed  Google Scholar 

  • Gopel SO et al (2000a) Regulation of glucagon release in mouse alpha-cells by KATP channels and inactivation of TTX-sensitive Na+ channels. J Physiol 528:509–520

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gopel SO, Kanno T, Barg S, Rorsman P (2000b) Patch-clamp characterization of somatostatin-secreting 5-cells in intact mouse pancreatic islets. J Physiol 528:497–507

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gribble FM, Reimann F (2003) Sulphonylurea action revisited: the post-cloning era. Diabetologia 46:875–891

    Google Scholar 

  • Gribble FM, Williams L, Simpson AK, Reimann F (2003) A novel glucose-sensing mechanism contributing to glucagon-like peptide-1 secretion from the GLUTag cell line. Diabetes 52:1147–1154

    CAS  PubMed  Google Scholar 

  • Gumina RJ et al (2003) Knockout of Kir6.2 negates ischemic preconditioning-induced protection of myocardial energetics. Am J Physiol Heart Circ Physiol 284:H2106–H2113

    CAS  PubMed  Google Scholar 

  • Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recordings from cells and cell-free membrane patches. Pflugers Arch 391:85–100

    CAS  PubMed  Google Scholar 

  • Henquin JC (2000) Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes 49:1751–1760

    Google Scholar 

  • Henquin JC, Meissner HP (1984) Effects of theophylline and dibutyryl cyclic adenosine monophosphate on the membrane potential of mouse pancreatic β-cells. J Physiol 351:595–612

    CAS  PubMed Central  PubMed  Google Scholar 

  • Henquin JC, Schmeer W, Henquin M, Meissner HP (1984) Forskolin suppresses the slow cyclic variations of glucose-induced electrical activity in pancreatic β cells. Biochem Biophys Res Commun 120:797–803

    CAS  PubMed  Google Scholar 

  • Henquin JC, Schmeer W, Henquin M, Meissner HP (1985) Effects of a calcium channel agonist on the electrical, ionic and secretory events in mouse pancreatic β-cells. Biochem Biophys Res Commun 131:980–986

    CAS  PubMed  Google Scholar 

  • Hu S, Wang S, Fanelli B, Bell PA, Dunning BE, Geisse S, Schmitz R, Boettcher BR (2000) Pancreatic β-cell KATP channel activity and membrane binding studies with nateglinide: a comparison with sulfonylureas and repaglinide. J Pharmacol Exp Ther 293:444–452

    CAS  PubMed  Google Scholar 

  • Huopio H et al (2000) Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type I. J Clin Invest 106:897–906

    CAS  PubMed Central  PubMed  Google Scholar 

  • Koster JC, Marshall BA, Ensor N, Corbett JA, Nichols CG (2000) Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes. Cell 100:645–654

    Google Scholar 

  • Lindau M, Neher E (1988) Patch-clamp techniques for time-resolved capacitance measurements in single cells. Pflugers Arch 411:137–146

    CAS  PubMed  Google Scholar 

  • Maechler P, Wang H, Wollheim CB (1998) Continuous monitoring of ATP levels in living insulin secreting cells expressing cytosolic firefly luciferase. FEBS Lett 422:328–332

    CAS  PubMed  Google Scholar 

  • Maedler K, Spinas GA, Dyntar D (2001) Distinct effects of saturated and monounsaturated fatty acids on beta-cell turnover and function. Diabetes 50:69–76

    CAS  PubMed  Google Scholar 

  • Magge SN et al (2004) Familial leucine-sensitive hypoglycemia of infancy due to a dominant mutation of the beta-cell sulfonylurea receptor. J Clin Endocrinol Metab 89:4450–4456

    CAS  PubMed  Google Scholar 

  • Meissner HP (1990) Membrane potential measurements in pancreatic β cells with intracellular microelectrodes. Methods Enzymol 192:235–246

    CAS  PubMed  Google Scholar 

  • Miki T et al (2001) ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis. Nat Neurosci 4:507–512

    CAS  PubMed  Google Scholar 

  • Mulder H, Holst LS, Svensson H (1999) Hormone-sensitive lipase deficiency in mouse islets abolishes neutral cholesterol ester hydrolase activity but leaves lipolysis, acylglycerides, fat oxidation, and insulin secretion intact. Endocrinology 145:3746–3753

    Google Scholar 

  • Niki I, Kelly RP, Ashcroft SJH, Ashroft FM (1989) ATP-sensitive K-channels in HIT T15 β-cells studied by patchclamp methods, 86Rb efflux and glibenclamide binding. Pflügers Arch 415:47–55

    Google Scholar 

  • Poitout V, Robertson RP (2002) Minireview: secondary beta-cell failure in type 2 diabetes-a convergence of glucotoxicity and lipotoxicity. Endocrinology 143:339–342

    CAS  PubMed  Google Scholar 

  • Prentki M, Corkey BE (1996) Are the beta-cell signalling molecules malonyl-CoA and cytosolic long-chain acyl-CoA implicated in multiple tissue defects of obesity and NIDDM? Diabetes 45:1086–1094

    Google Scholar 

  • Rajan AS, Aguilar-Bryan L, Nelson DA, Nichols CG, Wechsler SW, Lechago J, Bryan J (1993a) Sulfonylurea receptors and ATP-sensitive K+ channels in clonal pancreatic β cells. Evidence for two high affinity sulfonylurea receptors. J Biol Chem 268:15221–15228

    CAS  PubMed  Google Scholar 

  • Randle PJ, Garland PB, Hales CN, Newsholme EA (1963) The glucose fatty acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785–789

    CAS  PubMed  Google Scholar 

  • Roche E, Farfari S, Witters LA (1998) Long-term exposure of beta-INS cells to high glucose concentrations increases anaplerosis, lipogenesis, and lipogenic gene expression. Diabetes 47:1086–1094

    CAS  PubMed  Google Scholar 

  • Roduit R, Masiello P, Wang SP, Li H, Mitchell GA, Prentki M (2001) A role for hormone-sensitive lipase in glucose-stimulated insulin secretion. A study in hormone-sensitive lipase-deficient mice. Diabetes 50:1970–1975

    Google Scholar 

  • Rorsman P, Trube G (1985) Glucose dependent K+ channels in pancreatic B-cells are regulated by intracellular ATP. Pflugers Arch 405:305–309

    CAS  PubMed  Google Scholar 

  • Rorsman P, Bokvist K, Ämmälä C, Eliasson L, Renström E, Gäbel J (1994) Ion channels, electrical activity and insulin secretion. Diabete Metab (Paris) 20:138–145

    CAS  Google Scholar 

  • Rubi B, Ishihara H, Hegardt FG, Wollheim CB, Maechler P (2001) GAD65-mediated glutamate decarboxylation reduces glucose-stimulated insulin secretion in pancreatic β cells. J Biol Chem 276:36391–36396

    CAS  PubMed  Google Scholar 

  • Seghers V, Nakazaki M, DeMayo F, Aguilar-Bryan L, Bryan J (2000) Sur1 knockout mice. A model for K(ATP) channel-independent regulation of insulin secretion. J Biol Chem 275:9270–9277

    CAS  PubMed  Google Scholar 

  • Seino S, Miki T (2004) Gene targeting approach to clarification of ion channel function: studies of Kir6.x null mice. J Physiol 554:295–300

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shieh C-C, Feng J, Buckner SA, Brioni JD, Coghlan MJ, Sullivan JP, Gopalakrishnan M (2000) Functional implication of spare ATP-sensitive K+ channels in bladder smooth muscle cells. J Pharmacol Exp Ther 296:669–675

    Google Scholar 

  • Shindo T, Katayama Y, Horio Y, Kurachi Y (2000) MCC-134, a novel vascular relaxing agent, is an inverse agonist for the pancreatic-type ATP-sensitive K+ channel. J Pharmacol Exp Ther 292:131–135

    CAS  PubMed  Google Scholar 

  • Thomas P, Ye Y, Lightner E (1996) Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemia hypoglycemia of infancy. Hum Mol Genet 5:1809–1812

    CAS  PubMed  Google Scholar 

  • Unger RH, Orci L (2002) Lipoapoptosis: its mechanism and its diseases. Biochim Biophys Acta 1585:202–212

    CAS  PubMed  Google Scholar 

  • Wang W, Giebisch G (1991) Dual modulation of renal ATP-sensitive K+ channel by protein kinases A and C. Proc Natl Acad Sci U S A 88:9722–9725

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang L, Folsom AR, Zheng ZJ, Pankow JS, Eckfeldt JH (2003) Plasma fatty acid composition and incidence of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr 78:91–98

    CAS  PubMed  Google Scholar 

  • Yamada K et al (2001) Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure. Science 292:1543–1546

    CAS  PubMed  Google Scholar 

  • Zhou YP, Grill VE (1994) Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle. J Clin Invest 93:870–876

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zingman LV et al (2002) Kir6.2 is required for adaptation to stress. Proc Natl Acad Sci U S A 99:13278–13283

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zünkler BJ, Lenzen S, Männer K, Panten U, Trube G (1988) Concentration-dependent effects of tolbutamide, meglitinide, glipizide, glibenclamide and diazoxide on ATP-regulated K+ currents in pancreatic B-cells. Naunyn Schmiedebergs Arch Pharmacol 337:225–230

    PubMed  Google Scholar 

Interaction with β-Cell Plasma Membranes and KATP Channels

  • Aguilar-Bryan L, Bryan J (1999) Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocr Rev 20:101–135

    CAS  PubMed  Google Scholar 

  • Aguilar-Bryan L, Nelson DA, Vu QA, Humphrey MB (1990) Photoaffinity labeling and partial purification of the b cell sulfonylurea receptor using a novel, biologically active glyburide analog. J Biol Chem 265:8218–8224

    CAS  PubMed  Google Scholar 

  • Aguilar-Bryan L, Nichols CG, Rajan AS, Parker C, Bryan J (1992) Co-expression of sulfonylurea receptors and KATP channels in hamster insulinoma tumor (HIT) cells. Evidence for direct association of the receptor with the channel. J Biol Chem 267:14934–14940

    CAS  Google Scholar 

  • Aguilar-Bryan L et al (1995) Cloning of the β-cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science 268:423–426

    CAS  PubMed  Google Scholar 

  • Aguilar-Bryan L, Clement JP, Gonzalez G, Kunjilwar K, Babenko A, Bryan J (1998) Toward understanding the assembly and structure of KATP channels. Physiol Rev 78:227–245

    CAS  PubMed  Google Scholar 

  • Angel I, Bidet S (1991) The binding site for [3H]glibenclamide in the rat cerebral cortex does not recognize K-channel agonists or antagonists other than sulfonylureas. Fundam Clin Pharmacol 5:107–115

    CAS  PubMed  Google Scholar 

  • Ashcroft FM (2005) ATP-sensitive potassium channelopathies: focus on insulin secretion. J Clin Invest 115:2047–2058

    Google Scholar 

  • Ashcroft SJH, Ashcroft FM (1992) The sulfonylurea receptor. Biochim Biophys Acta 1175:45–59

    CAS  PubMed  Google Scholar 

  • Ashfield R, Gribble FM, Ashcroft SJ, Ashcroft FM (1999) Identification of the high-affinity tolbutamide site on the SUR1 subunit of the K(ATP) channel. Diabetes 48:1341–1347

    CAS  PubMed  Google Scholar 

  • Babenko AP, Aguilar-Bryan L, Bryan J (1998) A view of SUR/KIR6.X, KATP channels. Annu Rev Physiol 60:667–687

    CAS  PubMed  Google Scholar 

  • Babenko AP, Gonzalez G, Bryan J (1999) The tolbutamide site of SUR1 and a mechanism for its functional coupling to KATP channel closure. FEBS Lett 459:367–376

    CAS  PubMed  Google Scholar 

  • Bähr M, von Holtey M, Müller G, Eckel J (1995) Direct stimulation of myocardial glucose transport and glucose transport-1 (GLUT1) and GLUT4 protein expression by the sulfonylurea glimepiride. Endocrinology 136:2547–2553

    PubMed  Google Scholar 

  • Bernardi H, Fosset M, Lazdunski M (1988) Characterization, purification, and affinity labeling of the brain [3H]glibenclamide-binding protein, a putative neuronal ATP-regulated K+ channel. Proc Natl Acad Sci U S A 85:9816–9820

    CAS  PubMed Central  PubMed  Google Scholar 

  • Boyd AE 3rd (1992) The role of ion channels in insulin secretion. J Cell Biochem 48:235–241

    PubMed  Google Scholar 

  • Boyd AE III, Aguilar-Bryan L, Bryan J, Kunze DL, Moss L, Nelson DA, Rajan AS, Raef H, Xiang H, Yaney GC (1991) Sulfonylurea signal transduction. Recent Prog Horm Res 47:299–317

    Google Scholar 

  • Bryan J, Aguilar-Bryan L (1997) The ABCs of ATP-sensitive potassium channels. Curr Opin Cell Biol 9:553–559

    Google Scholar 

  • Bryan J, Aguilar-Bryan L (1999) Sulfonylurea receptors: ABC transporters that regulate ATP-sensitive K+ channels. Biochim Biophys Acta 1461:285–303

    CAS  PubMed  Google Scholar 

  • Bryan LA, Nichols CG, Wechsler SW, Clement JP, Boyd AE, Gonzales G, Sosa HH, Nguy K, Bryan J, Nelson DA (1995) Cloning of the β cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science 268:423–426

    PubMed  Google Scholar 

  • Chutkow WA, Simon MC, Beau MML, Burant CF (1996) Cloning, tissue expression, and chromosomal localization of SUR2, the putative drug-binding subunit of cardiac, skeletal muscle and vascular KATP channels. Diabetes 45:1439–1445

    Google Scholar 

  • Clement JP IV, Kunjilwar K, Gonzalez G, Schwanstecher M, Panten U, Aguilar-Bryan L, Bryan J (1997) Association and stoichiometry of KATP channel subunits. Neuron 18:827–838

    CAS  PubMed  Google Scholar 

  • Cooper DR, Vila MC, Watson JE, Nair G, Pollet RJ, Standaert M, Farese RV (1990) Sulfonylurea-stimulated glucose transport association with diacylglycerol-like activation of protein kinase C in BC3H1 myocytes. Diabetes 39:1399–1407

    CAS  PubMed  Google Scholar 

  • Davidson MB, Molnar IG, Furman A, Yamaguchi D (1991) Glyburide-stimulated glucose transport in cultured muscle cells via protein kinase C-mediated pathway requiring new protein synthesis. Diabetes 40:1531–1538

    CAS  PubMed  Google Scholar 

  • Gaines KL, Hamilton S, Boyd AE III (1988) Characterization of the sulfonylurea receptor on beta cell membranes. J Biol Chem 263:2589–2592

    CAS  PubMed  Google Scholar 

  • Geisen K, Hitzel V, Ökonomopoulos R, Pünter J, Weyer R, Summ HD (1985) Inhibition of 3H-glibenclamide binding to sulfonylurea receptors by oral antidiabetics. Arzneim Forsch/Drug Res 35:707–712

    CAS  Google Scholar 

  • Glaser B, Thornton P, Otonkoski T, Junien C (2000) Genetics of neonatal hyperinsulinism. Arch Dis Child Fetal Neonatal Ed 82:F79–F86

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gribble FM, Reimann F (2003) Sulphonylurea action revisited: the post-cloning era. Diabetologia 46:875–891

    Google Scholar 

  • Gribble FM, Tucker SJ, Ashcroft FM (1997) The essential role of the Walker A motifs of SUR1 in KATP channel activation by MgADP and diazoxide. EMBO J 16:1145–1152

    CAS  PubMed Central  PubMed  Google Scholar 

  • Grynkiewicz G, Pocnic M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescent properties. J Biol Chem 260:3440–3450

    CAS  PubMed  Google Scholar 

  • Henquin JC (2000) Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes 49:1751–1760

    Google Scholar 

  • Inagaki N et al (1995) Cloning and functional characterisation of a novel ATP-sensitive potassium channel ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle, and heart. J Biol Chem 270:5691–5694

    CAS  PubMed  Google Scholar 

  • Inagaki N et al (1996) A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels. Neuron 16:1011–1017

    CAS  PubMed  Google Scholar 

  • Isomoto S et al (1996) A novel sulfonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K+ channel. J Biol Chem 271:24321–24324

    CAS  PubMed  Google Scholar 

  • Kaubisch N, Hammer R, Wollheim C, Renold AE, Offord R (1982) Specific receptors for sulfonylureas in brain and in a β-cell tumor of the rat. Biochem Pharmacol 31:1171–1174

    CAS  PubMed  Google Scholar 

  • Klip A, Ramlal RJ, Douen AG, Burdett E, Young D, Cartee GD, Holloszy JO (1987) Insulin-induced decrease in 5′-nucleotidase activity in skeletal muscle membranes. FEBS Lett 238:419–423

    Google Scholar 

  • Koster JC, Marshall BA, Ensor N, Corbett JA, Nichols CG (2000) Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes. Cell 100:645–654

    Google Scholar 

  • Kramer W, Oekonomopulos R, Punter J, Summ HD (1988) Direct photolabeling of the putative sulfonylurea receptor in rat b-cell tumor membranes by [3H]glibenclamide. FEBS Lett 229:355–359

    CAS  PubMed  Google Scholar 

  • Kramer W, Müller G, Girbig F, Gutjahr U, Kowalewski S, Hertz D, Summ HD (1994) Differential interaction of glimepiride and glibenclamide with the β-cell sulfonylurea receptor. II. Photoaffinity labeling. Biochim Biophys Acta 119:278–290

    Google Scholar 

  • Masuda K, Okamoto Y, Tsuura Y, Kato S, Miura T, Tsuda K, Horikoshi H Ishida H, Seino Y (1995) Effects of Troglitazone (CS-045) on insulin secretion in isolated rat pancreas islets and HIT cells. an insulintropic mechanism distinct from glibenclamide. Diabetologia 38:24–30

    CAS  PubMed  Google Scholar 

  • Müller G (2000) The molecular mechanism of the insulin-mimetic/sensitizing activity of the antidiabetic sulfonylurea drug amaryl. Mol Med 6:907–933

    PubMed Central  PubMed  Google Scholar 

  • Müller G (2002) Dynamics of plasma membrane microdomains and cross-talk to the insulin signaling cascade. FEBS Lett 531:81–87

    PubMed  Google Scholar 

  • Müller G (2005) The mode of action of the antidiabetic drug glimepiride-beyond insulin secretion. Curr Med Chem Immunol Endocrinol Metab Agents 5:499–518

    Google Scholar 

  • Müller G, Geisen K (1996) Characterization of the molecular mode of action of the sulfonylurea, glimepiride, at adipocytes. Horm Metab Res 28:469–487

    PubMed  Google Scholar 

  • Müller G, Welte S (2002) Lipid raft domains are the targets for the insulin-independent blood glucose-decreasing activity of the sulfonylurea glimepiride. Recent Res Dev Endocrinol 3:401–423

    Google Scholar 

  • Müller G, Hartz D, Pünter J, Ökonomopoulos R, Kramer W (1994a) Differential interaction of glimepiride and glibenclamide with the β-cell sulfonylurea receptor. I. Binding characteristics. Biochim Biophys Acta 1191:267–277

    PubMed  Google Scholar 

  • Müller G, Wied S, Wetekam EM, Crecelius A, Punter J (1994b) Stimulation of glucose utilization in 3T3 adipocytes and rat diaphragm in vitro by the sulfonylureas glimepiride and glibenclamide, is correlated with modulations of the cAMP regulatory cycle. Biochem Pharmacol 48:985–996

    PubMed  Google Scholar 

  • Müller G, Jung C, Wied S, Welte S, Jordan H, Frick W (2001) Redistribution of glycolipid raft domain components induces insulin-mimetic signaling in rat adipocytes. Mol Cell Biol 21:4553–4567

    PubMed Central  PubMed  Google Scholar 

  • Panten U (1989) Mechanism of insulin secretion and its modulation by sulfonylureas. Contrib Nephrol 73:16–21.

    CAS  PubMed  Google Scholar 

  • Panten U, Schwanstecher M, Schwanstecher C (1992) Pancreatic and extrapancreatic sulfonylurea receptors. Horm Metab Res. 24:549–554.

    CAS  PubMed  Google Scholar 

  • Philipson LH (1995) ATP-sensitive K+ channels: paradigm lost, paradigm regained. Science 270:1159

    CAS  PubMed  Google Scholar 

  • Rajan AS, Aguilar-Bryan L, Nelson DA, Nichols CG, Wechsler SW, Lechago J, Bryan J (1993b) Sulfonylurea receptors and ATP-sensitive K+ channels in clonal pancreatic β cells. Evidence for two high affinity sulfonylurea receptors. J Biol Chem 268:15221–15228

    CAS  PubMed  Google Scholar 

  • Rogers BJ, Standaert ML, Pollet (1987) Direct effects of sulfonylurea agents on glucose transport in the BC3H1 myocyte. Diabetes 39:1292–1296

    Google Scholar 

  • Sakura H, Ammala C, Smith PA, Gribble FM, Ashcroft FM (1995) Cloning and functional expression of the cDNA encoding a novel ATP-sensitive potassium channel subunit expressed in pancreatic β-cells, brain, heart and skeletal muscle. FEBS Lett 377:338–344

    CAS  PubMed  Google Scholar 

  • Schmid-Antomarchi H, DeWeille J, Fosset M, Lazdunski M (1987a) The receptor for the antidiabetic sulfonylureas controls the activity of the ATP-modulated K+-channels in insulin-secreting cells. J Biol Chem 262:15840–15844

    CAS  PubMed  Google Scholar 

  • Schmid-Antomarchi H, DeWeille J, Fosset M, Lazdunski M (1987b) The antidiabetic sulfonylurea glibenclamide is a potent blocker of the ATP-modulated K+-channel in insulin-secreting cells. Biochem Biophys Res Commun 146:21–25

    CAS  PubMed  Google Scholar 

  • Schwanstecher C, Panten U (1993) Tolbutamide- and diazoxide-sensitive K+ channel in neurons of substantia nigra pars reticulata. Naunyn Schmiedebergs Arch Pharmacol 348:113–117

    CAS  PubMed  Google Scholar 

  • Shi H, Moustaid-Moussa N, Wilkison WO, Zemel MB (1999) Role of the sulfonylurea receptor in regulating human adipocyte metabolism. FASEB J 13:1833–1838

    CAS  PubMed  Google Scholar 

  • Shyng SL, Nichols GG (1997) Octameric stoichiometry of the KATP channel complex. J Gen Physiol 110:655–664

    CAS  PubMed Central  PubMed  Google Scholar 

  • Skeer JM, Degano P, Coles B, Potier M, Ashcroft FM, Ashcroft SJH (1994) Determination of the molecular mass of the native beta-cell sulfonylurea receptor. FEBS Lett 338:98–102

    CAS  PubMed  Google Scholar 

  • Tanabe K et al (1999) Direct photoaffinity labeling of the Kir6.2 subunit of the ATP-sensitive K+ channel by 8-azido-ATP. J Biol Chem 274:3931–3933

    CAS  PubMed  Google Scholar 

  • Ueda K, Komine J, Matsuo M, Seino S, Amachi T (1999) Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide. Proc Natl Acad Sci U S A 96:1268–1272

    CAS  PubMed Central  PubMed  Google Scholar 

  • Uhde I, Toman A, Gross I, Schwanstecher C, Schwanstecher M (1999) Identification of the potassium channel opener site on sulfonylurea receptors. J Biol Chem 274:28079–28082

    CAS  PubMed  Google Scholar 

  • Wang PH, Beguinot F, Smith RJ (1987) Augmentation of the effects of insulin and insulin-like growth factors I and II on glucose uptake in cultured rat skeletal muscle cells by sulfonylureas. Diabetologia 30:797–803

    CAS  PubMed  Google Scholar 

  • Wang PH, Moller D, Flier JS, Nayak RC, Smith RJ (1989) Coordinate regulation of glucose transporter function, number, and gene expression by insulin and sulfonylureas in L6 skeletal muscle cells. J Clin Invest 84:62–67

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wessel D, Flügge UI (1984) A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids. Anal Biochem 138:141–143

    CAS  PubMed  Google Scholar 

  • Yip CC (1984) Photoaffinity probes for hormone receptor characterization. In: Larner J, Pohl SL (eds) Methods in diabetes research, vol I, Laboratory methods, Part A. Wiley, New York, pp 3–14

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Günter Müller .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Berlin Heidelberg

About this entry

Cite this entry

Müller, G. (2015). Assays for the Expression and Release of Insulin and Glucose-Regulating Peptide Hormones from Pancreatic β-Cell. In: Hock, F. (eds) Drug Discovery and Evaluation: Pharmacological Assays. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27728-3_158-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-27728-3_158-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Online ISBN: 978-3-642-27728-3

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics