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Glucose-induced Ca2+ (i) abnormalities in human pancreatic islets - Important role of overstimulation
KTH, Superseded Departments, Numerical Analysis and Computer Science, NADA.
2000 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 49, no 11, 1840-1848 p.Article in journal (Refereed) Published
Abstract [en]

Chronic hyperglycemia desensitizes beta -cells to glucose. To further define the mechanisms behind desensitization and the role of overstimulation, we tested human pancreatic islets for the effects of long-term elevated glucose levels on cytoplasmic free Ca2+ concentration ([Ca2+](i)) and its relationship to overstimulation. Islets were cultured for 48 h with 5.5 or 27 mmol/l glucose. Culture with 27 mmol/l glucose obliterated postculture insulin responses to 27 mmol/l glucose. This desensitization was specific for glucose versus arginine, Desensitization was accompanied by three major [Ca2+](i) abnormalities: 1) elevated basal [Ca2+](i),) loss of a glucose-induced rise in [Ca2+](i) and 3) perturbations of oscillatory activity with a decrease in glucose-induced slow oscillations (0.2-0.5 min(-1)). Coculture with 0.3 mmol/l diazoxide was performed to probe the role of overstimulation. Neither glucose nor diazoxide affected islet glucose utilization or oxidation, Coculture with diazoxide and 27 mmol/l glucose significantly (P < 0.05) restored postculture insulin responses to glucose and lowered basal [Ca2+](i) and normalized glucose-induced oscillatory activity. However, diazoxide completely failed to revive an increase in [Ca2+](i) during postculture glucose stimulation. In conclusion, desensitization of glucose-induced insulin secretion in human pancreatic islets is induced in parallel with major glucose-specific [Ca2+](i) abnormalities. Overstimulation is an important but not exclusive factor behind [Ca2+](i) abnormalities.

Place, publisher, year, edition, pages
2000. Vol. 49, no 11, 1840-1848 p.
Keyword [en]
beta-cells, insulin release, cytoplasmic ca2+, b-cell, calcium-concentration, induced oscillations, prolonged exposure, glucagon-secretion, mouse, diazoxide
URN: urn:nbn:se:kth:diva-20144ISI: 000165123700011OAI: diva2:338837
QC 20100525Available from: 2010-08-10 Created: 2010-08-10Bibliographically approved

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