Journal of Clinical Endocrinology & Metabolism, Vol 72, 202-208, Copyright © 1991 by Endocrine Society

ARTICLES

Abnormal sensitivity to glucose of human islets cultured in a high glucose medium: partial reversibility after an additional culture in a normal glucose medium

AM Davalli, C Ricordi, C Socci, S Braghi, F Bertuzzi, B Fattor, V Di Carlo, AE Pontiroli and G Pozza
Istituto Scientifico San Raffaele, Cattedra di Clinica Medica, Universita di Milano, Italy.

In the experimental animal chronic hyperglycemia alters the islet's sensitivity to glucose. In the present study the glucose sensitivity of human pancreatic islets, isolated and purified, obtained from seven human pancreases using an automated method was evaluated. After a 12-h stabilization period, islets were cultured for 48 h in normal (5.5 mmol/L) or high glucose (16.7 mmol/L) medium. Islets were then perifused to study their insulin response to glucose. Islets cultured in the high glucose medium lost glucose-induced insulin release and, when challenged with an acute fall of glucose concentration in the perifusate, showed a paradoxical insulin release. Insulin release in response to 10 mmol/L L-arginine was preserved in these islets, suggesting a selective reduction of the insulin response to glucose. An additional 48-h culture in 5.5 mmol/L glucose medium partially restored the sensitivity to glucose of the previously unresponsive islets. These findings indicate that short term exposure to high glucose concentrations induces a selective glucose insensitivity of human islets, which can be partially reversed by an additional culture in normal glucose medium.

This article has been cited by other articles:

				M. A. Kiraly, H. E. Bates, N. A. Kaniuk, J. T. Y. Yue, J. H. Brumell, S. G. Matthews, M. C. Riddell, and M. Vranic Swim training prevents hyperglycemia in ZDF rats: mechanisms involved in the partial maintenance of {beta}-cell function Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E271 - E283. [Abstract] [Full Text] [PDF]

				F. Bertuzzi and C. Ricordi Prediction of Clinical Outcome in Islet Allotransplantation Diabetes Care, February 1, 2007; 30(2): 410 - 417. [Full Text] [PDF]

				J.-C. Henquin, D. Dufrane, and M. Nenquin Nutrient Control of Insulin Secretion in Isolated Normal Human Islets Diabetes, December 1, 2006; 55(12): 3470 - 3477. [Abstract] [Full Text] [PDF]

				S. Kooptiwut, M. Kebede, S. Zraika, S. Visinoni, K. Aston-Mourney, J. Favaloro, C. Tikellis, M. C Thomas, J. M Forbes, M. E Cooper, et al. High glucose-induced impairment in insulin secretion is associated with reduction in islet glucokinase in a mouse model of susceptibility to islet dysfunction J. Mol. Endocrinol., August 1, 2005; 35(1): 39 - 48. [Abstract] [Full Text] [PDF]

				D. MELLOUL Transcription Factors in Islet Development and Physiology: Role of PDX-1 in Beta-Cell Function Ann. N.Y. Acad. Sci., April 1, 2004; 1014(1): 28 - 37. [Abstract] [Full Text] [PDF]

				J.-C. Henquin, N. Ishiyama, M. Nenquin, M. A. Ravier, and J.-C. Jonas Signals and Pools Underlying Biphasic Insulin Secretion Diabetes, February 1, 2002; 51(90001): S60 - 67. [Abstract] [Full Text] [PDF]

				M. Federici, M. Hribal, L. Perego, M. Ranalli, Z. Caradonna, C. Perego, L. Usellini, R. Nano, P. Bonini, F. Bertuzzi, et al. High Glucose Causes Apoptosis in Cultured Human Pancreatic Islets of Langerhans: A Potential Role for Regulation of Specific Bcl Family Genes Toward an Apoptotic Cell Death Program Diabetes, June 1, 2001; 50(6): 1290 - 1301. [Abstract] [Full Text]

				C. E. Gleason, M. Gonzalez, J. S. Harmon, and R. P. Robertson Determinants of glucose toxicity and its reversibility in the pancreatic islet beta -cell line, HIT-T15 Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E997 - E1002. [Abstract] [Full Text] [PDF]

				A. M. Davalli, P. Maffi, C. Socci, F. Sanvito, M. Freschi, F. Bertuzzi, L. Falqui, V. Di Carlo, G. Pozza, and A. Secchi Insights from a Successful Case of Intrahepatic Islet Transplantation into a Type 1 Diabetic Patient J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3847 - 3852. [Abstract] [Full Text]