Threshold for glucose-stimulated insulin secretion in pancreatic islets of genetically obese (ob/ob) mice is abnormally low.
Pancreatic islets were isolated from 8-9-wk-old female genetically obese (ob/ob) and lean mice to determine the glucose threshold for insulin secretion, and to examine effects of acetylcholine on insulin secretion. Only equal-sized islets from ob/ob and lean mice were incubated to eliminate confounding effects of phenotypic differences in islet size. Even after this adjustment, islets from ob/ob mice still hypersecreted insulin in response to 20 mmol/L glucose. The threshold for glucose-induced insulin secretion determined by perifusing islets with a linear glucose gradient averaged 1.9 +/- 0.1 mmol/L glucose in fed ob/ob mice and 3.1 +/- 0.1 mmol/L glucose in ob/ob mice after 24 h of food deprivation. These low thresholds indicate that islets from ob/ob mice are constantly stimulated by glucose. Islets from lean mice exhibited considerably higher thresholds (4.8 +/- 0.1 and 7.1 +/- 0.1 mmol/L glucose in fed and 24-h food-deprived lean mice, respectively). Rates of insulin secretion per each unit (mmol/L) increase in glucose above threshold concentrations were unaffected by phenotype or feeding state. Addition of acetylcholine to the perifusing buffer further lowered the threshold for insulin secretion to 0.5 mmol/L glucose in pancreatic islets from ob/ob mice and also doubled the rate of increase in insulin secretion at glucose concentrations above the threshold. The combination of the very low threshold for glucose-induced insulin secretion and the exaggerated insulin secretory response to acetylcholine in pancreatic islets of ob/ob mice are likely critical factors in the hyperinsulinemia of these mice.
Chen
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NG
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824-1224.
Tassava
T M
TM
Romsos
D R
DR
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose; D000109:Acetylcholine