Summary
In vitro islet exposure to interleukin 1β inhibits the beta-cell response to glucose. We have studied whether a similar inhibition also occurs in response to the sulphonylurea glyburide. Rat pancreatic islets were cultured for 24 h in the presence or absence of 50 U/ml interleukin 1β and then stimulated with either glucose or glyburide for 1 h at 37 °C. In control islets basal insulin secretion was 117±32 pg · islet−1 · h−1 (mean ± SEM, n=7) and greatly increased in response to 16.7 mmol/l glucose (2140±293) or 10 μmol/l glyburide (1464±234). When islets were pre-exposed to interleukin 1β, insulin release was significantly reduced in response to glucose (323±80, p<0.001) but not in response to glyburide (1316±185). Since both glucose and glyburide influence beta-cell K+ and Ca2+ efflux, to further investigate this different response in islets exposed to interleukin 1β we measured both Rb+ efflux (as index of the ATP-sensitive K+ channel activity) and Ca2+ uptake. In control islets, the increased insulin secretion in response to 16.7 mmol/l glucose or 10 μmol/l glyburide was associated with a reduction of 86Rb efflux (decrement of −50±1.2 % and −49±2.3 %, respectively, mean ± SEM, n=5). In contrast, in interleukin 1βpre-exposed islets both glucose and glyburide stimulation only slightly modified 86Rb efflux (decrement of −19±1.9% and −5.3±3.1 %, respectively, n=5, p<0.001). 45Ca2+ uptake in control islets was 2.6±0.4 pmol · islet−1 · 20 min−1 under basal conditions (at 2.8 mmol/l glucose), and increased to 16.8±3.2 and 10.7±2.1 pmol · islet−1 · 20 min−1 in islets stimulated with 16.7 mmol/l glucose or 10 μmol/l glyburide, respectively (mean ± SEM, n=6). 45Ca2+ uptake in interleukin 1β treated islets was higher than in control islets under basal conditions (4.6±0.6 pmol · islet−1 · 20 min−1 at 2.8 mmol/l glucose, p<0.05), but was significantly reduced in response to glucose 16.7 mmol/l (7.1±1.1, p<0.01 with respect to control islets). In contrast to glucose, 10 μmol/l glyburide was able to stimulate calcium uptake in interleukin 1β treated islets in a similar way to control islets (12.8±2.5). The present data demonstrate that rat pancreatic islets treated with interleukin 1β for 24 h lose their responsivity to glucose, but not to glyburide. The difference between the two secretagogues is associated with the persistent ability of glyburide to influence Ca2+ uptake even in islets with impaired K+-channel function.
Article PDF
Similar content being viewed by others
References
Gepts W (1965) Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 14: 619–633
Eisenbarth GS (1986) Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med 314: 1360–1368
Maclaren NK (1981) Autoimmunity and diabetes. In: Cooperstein SJ, Watkins D (eds) The islets of Langerhans. Academic Press, New York, pp 453–466
Dinarello CA (1984) Interleukin 1 and the pathogenesis of the acute-phase response. N Engl J Med 311: 1413–1418
Mandrup-Poulsen T, Bendtzen K, Nielsen JH, Bendixen G, Nerup J (1985) Cytokines cause functional and structural damage to isolated islets of Langerhans. Allergy 40: 424–429
Mandrup-Poulsen T, Bendtzen K, Nerup J, Dinarello CA, Svenson M, Nielsen JH (1986) Affinity-purified human interleukin 1 is cytotoxic to islets of Langerhans. Diabetologia 29: 63–67
Zawalich WS, Diaz VA (1986) Interleukin-1 inhibits insulin secretion from isolated perifused rat islets. Diabetes 35: 1119–1123
Sandler S, Andersson A, Hellerström C (1987) Inhibitory effects of interleukin 1 on insulin secretion, insulin biosynthesis and oxidative metabolism of isolated rat pancreatic islets. Endocrinology 121: 1424–1431
Comens PG, Wolf PA, Unanue ER, Lacy PE, McDaniel ML (1987) Interleukin 1 is potent modulator of insulin secretion from isolated rat islet of Langerhans. Diabetes 36: 963–970
Rabinovitch A, Pukel C, Baquerizo H (1988) Interleukin-1 inhibits glucose-modulated insulin and glucagon secretion in rat islets monolayer cultures. Endocrinology 122: 2393–2397
Mandrup-Poulsen T, Helqvist S, Wogensen LD et al. (1990) Cytokines and free radicals as effector molecules in the destruction of pancreatic beta cells. Curr Top Microbiol Immunol 164: 169–193
Eizirik DL, Strandell E, Bendtzen K, Sandler S (1988) Functional characteristics of rat pancreatic islets maintained in culture following exposure to human interleukin 1. Diabetes 37: 916–919
Eizirik DL, Sandler S, Hallberg A, Bendtzen K, Sener A, Malaisse WJ (1989) Differential sensitivity to β-cell secretagogues in cultured rat pancreatic islets exposed to human interleukin-1β. Endocrinology 125: 752–759
Purrello F, Vetri M, Gatta C, Gullo D Vigneri R (1989) Effects of high glucose on insulin secretion by isolated rat islets and purified B-cells and possible role of glycosylation. Diabetes 38: 1417–1422
Henquin JC, Lambert AE (1975) Cobalt inhibition of insulin secretion and calcium uptake by isolated rat islets. Am J Physiol 228: 1669–1677
Flatt PR, Berggren PO, Gylfe E, Hellman BO (1980) Calcium and pancreatic B-cell function. IX. Demonstration of lanthanidinduced inhibition of insulin secretion independent of modifications in transmembrane Ca+ fluxes. Endocrinology 107: 1007–1013
Malaisse WJ, Giroix MH, Zahner D, Marynissen G, Sener A, Portha B (1991) Neonatal streptozotocin injection: a model of glucotoxicity? Metabolism 40: 1101–1105
Henquin JC (1978) D-Glucose inhibits potassium efflux from pancreatic slet cells. Nature 271: 271–273
Rabuazzo AM, Buscema M, Vinci C et al. (1992) Glyburide and tolbutamide induce desensitization of insulin release in rat pancreatic islets by different mechanisms. Endocrinology 131: 1815–1820
Henquin JC, Meissner HP (1982) Opposite effects of tolbutamide and diazoxide on 86Rb fluxes and membrane potential in pancreatic B-cells. Biochem Pharmacol 31: 1407–1415
Boyd AE (1988) Sulfonylurea receptors, ion channels and fruit flies. Diabetes 37: 847–850
Malaisse WJ, Lebrun P (1990) Mechanisms of sulfonylurea-induced insulin release. Diabetes Care 13 [Suppl 3]: 9–17
Siconolfi-Baez L, Banerj MA, Lebovitz HE (1990) Characterization and significance of sulfonylurea receptors. Diabetes Care 13 [Suppl 3]: 2–8
Sandler S, Bendtzen K, Borg LAH, Eizirik DL, Strandell E, Welsh N (1989) Studies on the mechanisms causing inhibition of insulin secretion in rat pancreatic islets exposed to human interleukin-1β indicate a perturbation in the mitochondrial function. Endocrinology 124: 1492–1501
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: 2608–2612
Smith PA, Rorsman P, Ashcroft FM (1989) Modulation of dihydropyridine-sensitive Ca2+ channels by glucose metabolism in mouse pancreatic β-cells. Nature 342: 550–553
Ganda OP, Srikanta S, Brink SJ et al. (1984) Differential sensitivity to β-cell secretagogues in “early” type I diabetes mellitus. Diabetes 33: 516–521
Bennett LE, Curry DL, Curry K (1973) Differences in insulin release in response to glucose and tolbutamide stimulation. Proc Soc Exp Biol Med 144: 436–439
Pfeiffer MA, Halter JB, Porte D Jr (1981) Insulin secretion of diabetes mellitus. Am J Med 70: 579–588
Serrano-Rios M, Ramos R, Rodriguez-Minon JL, Vivanco F (1970) Studies in prediabetes insulin response to oral glucose, intravenous tolbutamide and rapid intravenous glucose infusion in genetic prediabetics. Diabetologia 6: 392–398
Bleich D, Jackson RA, Soeldner JS, Eisenbarth GS (1990) Analysis of metabolic progression to type I diabetes in ICA+ relatives of patients with type I diabetes. Diabetes Care 13: 111–118
McCulloch DK, Koerker DJ, Kahn SE, Bonner-Weir S, Palmer JP (1991) Correlations of in vivo β-cell function tests with β-cell mass and pancreatic insulin content in streptozotocin-administered baboons. Diabetes 40: 673–679
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Buscema, M., Rabuazzo, A.M., Vinci, C. et al. Different effects of glucose and glyburide on insulin secretion in rat pancreatic islets pre-exposed to interleukin-1β. Possible involvement of K+ and Ca2+ channels. Diabetologia 36, 791–796 (1993). https://doi.org/10.1007/BF00400351
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00400351