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Evidence for defective glucose sensing by islets of fa/fa obese Zucker rats

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Abstract

The hypothesis that a defect in glucose sensing by islets of fa/fa Zucker rats contributes to hyperinsulinemia in these animals was tested. Islets from lean and fa/fa rats were isolated by collagenase digestion and step-density gradient purification and then cultured overnight in Dulbecco's modified Eagle's medium containing 12.5 mM glucose. Obese rat islets were more sensitive to hypoglycemic glucose levels with half-maximal effective concentration (EC50) of 5.6 mM compared with an EC50 of 8.2 mM for lean rat islets. In contrast, responsiveness of both phenotypes to alpha-ketoisocaproate and quinine was similar. Mannoheptulose did not inhibit insulin secretion from fa/fa islets, although inhibitors of later events in the stimulus-secretion coupling pathway were normally inhibited by iodoacetate and diazoxide. Finally, starvation in vivo and culture of islets in low glucose concentrations (5 mM) in vitro both decreased glucose-stimulated insulin secretion from lean but not fa/fa rat islets. We conclude that fa/fa rat islets have an exaggerated insulin response to hypoglycemic stimuli, possibly as a result of a defect in B-cell glucokinase function.LR: 20061115; PUBM: Print; JID: 0372712; 0 (Amino Acids); 0 (Blood Glucose); 0 (Iodoacetates); 11061-68-0 (Insulin); 130-95-0 (Quinine); 364-98-7 (Diazoxide); 50-99-7 (Glucose); 56-65-5 (Adenosine Triphosphate); 64-69-7 (Iodoacetic Acid); 654-29-5 (Mannoheptulose); EC 2.7.1.2 (Glucokinase); ppublishSource type: Electronic(1

Topics: Adenosine Triphosphate/pharmacology--Amino Acids/pharmacology--Animals--Blood Glucose/metabolism--Diazoxide/pharmacology--Female--Glucokinase/antagonists & inhibitors--Glucose/metabolism--Insulin/secretion--Iodoacetates/pharmacology--Iodoacetic Acid--Islets of Langerhans/metabolism--Mannoheptulose/pharmacology--Obesity/metabolism--Organ Culture Techniques--Quinine/pharmacology--Rats--Rats, Zucker--Starvation/metabolism
Publisher: 'Canadian Science Publishing'
DOI identifier: 10.1139/y93-005
OAI identifier: oai:islandscholar.ca:ir_ir-batch6-360
Provided by: IslandScholar
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