title: Mechanisms of glucose hypersensitivity in beta-cells from normoglycemic, partially pancreatectomized mice.
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.
authors.affiliation: Institute of Bioengineering and Department of Science and Technology, School of Medicine, University Miguel Hernandez, San Juan de Alicante, Alicante, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Martín
authors.forename: E
authors.initials: E
authors.lastname: Andreu
authors.forename: J M
authors.initials: JM
authors.lastname: Rovira
authors.forename: J A
authors.initials: JA
authors.lastname: Pertusa
authors.forename: M
authors.initials: M
authors.lastname: Raurell
authors.forename: C
authors.initials: C
authors.lastname: Ripoll
authors.forename: J V
authors.initials: JV
authors.lastname: Sanchez-Andrés
authors.forename: E
authors.initials: E
authors.lastname: Montanya
authors.forename: B
authors.initials: B
authors.lastname: Soria
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D004396:Coloring Agents / Q000378:metabolism; D004594:Electrophysiology; D005947:Glucose / Q000502:physiology*; D007515:Islets of Langerhans / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D010180:Pancreatectomy; D015221:Potassium Channels / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004396:Coloring Agents; D015221:Potassium Channels; D013778:Tetrazolium Salts; D013844:Thiazoles; D000255:Adenosine Triphosphate; C022616:thiazolyl blue; D005947:Glucose