Mechanisms of glucose hypersensitivity in beta-cells from normoglycemic, partially pancreatectomized mice

• Published in: Diabetes (New York, N.Y.) Vol. 48; no. 10; pp. 1954 - 1961
• Main Authors: MARTIN, F, ANDREU, E, ROVIRA, J. M, PERTUSA, J. A. G, RAURELL, M, RIPOLL, C, SANCHEZ-ANDRES, J. V, MONTANYA, E, SORIA, B
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.10.1999
• Subjects: Adenosine Triphosphate - metabolism; Animals; Biological and medical sciences; Blood Glucose - metabolism; Cells, Cultured; Coloring Agents - metabolism; Electrophysiology; Endocrine pancreas; Fundamental and applied biological sciences. Psychology; Glucose - physiology; Glucose metabolism; Islets of Langerhans - physiology; Male; Membrane Potentials; Mice; Mice, Inbred C57BL; Morphology. Functional localizations; Pancreatectomy; Pancreatic beta cells; Physiological aspects; Potassium Channels - metabolism; Tetrazolium Salts - metabolism; Thiazoles - metabolism; Vertebrates: endocrinology; Pancreatic hormone; Langerhans islet; Rodentia; Glucose; Insulin; Endocrine secretion; Vertebrata; Sensitivity; Mammalia; B-Cell; Mouse; Mechanism of action; Endocrine pancreas
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.48.10.1954

Mechanisms of glucose hypersensitivity in beta-cells from normoglycemic, partially pancreatectomized mice. F Martín , E Andreu , J M Rovira , J A Pertusa , M Raurell , C Ripoll , J V Sanchez-Andrés , E Montanya and B Soria Institute of Bioengineering and Department of Science and Technology, School of Medicine, University Miguel Hernandez, San Juan de Alicante, Alicante, Spain. Abstract Increased beta-cell sensitivity to glucose precedes the loss of glucose-induced insulin secretion in diabetic animals. Changes at the level of beta-cell glucose sensor have been described in these situations, but it is not clear whether they fully account for the increased insulin secretion. Using a euglycemic-normolipidemic 60% pancreatectomized (60%-Px) mouse model, we have studied the ionic mechanisms responsible for increased beta-cell glucose sensitivity. Two weeks after Px (Px14 group), Px mice maintained normoglycemia with a reduced beta-cell mass (0.88 +/- 0.18 mg) compared with control mice (1.41 +/- 0.21 mg). At this stage, the dose-response curve for glucose-induced insulin release showed a significant displacement to the left (P < 0.001). Islets from the Px14 group showed oscillatory electrical activity and cytosolic Ca2+ ([Ca2+]i) oscillations in response to glucose concentrations of 5.6 mmol/l compared with islets from the control group at 11.1 mmol/l. All the above changes were fully reversible both in vitro (after 48-h culture of islets from the Px14 group) and in vivo (after regeneration of beta-cell mass in islets studied 60 days after Px). No significant differences in the input resistance and ATP inhibition of ATP-sensitive K+ (K(ATP)) channels were found between beta-cells from the Px14 and control groups. The dose-response curve for glucose-induced MTT (C,N-diphenyl-N''-4,5-dimethyl thiazol 2 yl tetrazolium bromide) reduction showed a significant displacement to the left in islets from the Px14 group (P < 0.001). These results indicate that increased glucose sensitivity in terms of insulin secretion and Ca2+ signaling was not due to intrinsic modifications of K(ATP) channel properties, and suggest that the changes are most likely to be found in the glucose metabolism.