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Title: | Mechanisms of glucosa hypersensitivity in ß-cells from normoglycemic, partially pancreatectomized mice |
Author: | Martin, Franz Andreu, Etelvina Rovira, Juan Manuel Pertusa, Jose A. G. Raurell, Mercè Ripoll, Cristina Sanchez-Andres, Juan Vicente Montanya Mias, Eduard Soria, Bernat |
Keywords: | Glucosa Fisiologia Illots de Langerhans Ratolins (Animals de laboratori) Cèl·lules B Glucose Physiology Islands of Langerhans Mice (Laboratory animals) B cells |
Issue Date: | Oct-1999 |
Publisher: | American Diabetes Association |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.2337/diabetes.48.10.1954 |
It is part of: | Diabetes, 1999, vol. 48, num. 10, p. 1954-1961 |
URI: | http://hdl.handle.net/2445/135008 |
Related resource: | https://doi.org/10.2337/diabetes.48.10.1954 |
ISSN: | 0012-1797 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) |
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