Insulin Secretory Defect in Zucker fa/fa Rats Is Improved by Ameliorating Insulin Resistance
| Autor: | R. G. Ulrich, J. H. Yu, C. J. de Souza, M. D. Meglasson, D. D. Robinson |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Blood Glucose
Aging endocrine system medicine.medical_specialty medicine.drug_class Fasting hyperinsulinemia Tolbutamide Endocrinology Diabetes and Metabolism medicine.medical_treatment Fatty Acids Nonesterified Biology Islets of Langerhans Insulin resistance Reference Values Internal medicine Insulin Secretion Internal Medicine medicine Hyperinsulinemia Animals Hypoglycemic Agents Insulin Amino Acids Thiazolidinedione Pioglitazone medicine.disease Rats Rats Zucker Insulin oscillation Thiazoles Glucose Endocrinology Female Thiazolidinediones Insulin Resistance medicine.drug |
| Zdroj: | Diabetes. 44:984-991 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diab.44.8.984 |
| Popis: | The role of insulin resistance in the impaired glucosestimulated insulin release of Zucker fatty rats was investigated using the insulin-sensitizing thiazolidinedione drug pioglitazone. Fatty rats had fasting hyperinsulinemia yet a blunted secretory response to intravenous glucose compared with lean age-matched controls. Islets from fatty rats secreted less insulin (based on islet DNA) in response to high glucose than islets from lean rats but secreted normal amounts of insulin when tolbutamide or α-ketoisocaproic acid (α-KIC) was the stimulus. Administering pioglitazone for 9 days diminished basal hyperinsulinemia and increased the insulin response to high glucose by fatty rats but not by lean controls. Pioglitazone pretreatment augmented the secretory response by isolated islets to high glucose, α-KIC, and tolbutamide. Augmentation of islet insulin release was not associated with reduced plasma glucose concentration, suggesting that altered glycemia was not involved. Pancreas and islet insulin content was greater in fatty rats than in lean controls and was decreased by pioglitazone; hence, insulin stores and glucose-stimulated insulin release did not correlate. Pioglitazone treatment did not affect the rate of islet glucose usage or ATP/ADP in the presence of 2.75 or 16 mmol/1 glucose. These data indicate that ameliorating insulin resistance reverses defective glucosestimulated insulin release by Zucker fa/fa rats. After pioglitazone administration, insulin secretion may be augmented by increased generation of a metabolic coupling factor from glucose or at a later step in the secretory process that is common to both glucose and nonglucose secretagogues. |
| Databáze: | OpenAIRE |
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