Interaction between genetic and dietary factors determines beta-cell function in Psammomys obesus, an animal model of type 2 diabetes
| Autor: | Rafael Nesher, Nurit Kaiser, David J Gross, Erol Cerasi, Marc Y. Donath |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism medicine.medical_treatment Type 2 diabetes Biology Islets of Langerhans chemistry.chemical_compound Internal medicine Diabetes mellitus Internal Medicine medicine Animals Insulin Genetic Predisposition to Disease Phosphorylation geography Hexokinase geography.geographical_feature_category Dose-Response Relationship Drug Glucokinase Islet medicine.disease biology.organism_classification Diet Insulin oscillation Disease Models Animal Glucose Endocrinology Diabetes Mellitus Type 2 chemistry Animal Nutritional Physiological Phenomena Psammomys Food Deprivation Gerbillinae |
| Zdroj: | Diabetes. 48:731-737 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diabetes.48.4.731 |
| Popis: | The gerbil Psammomys obesus develops nutrition-dependent diabetes. We studied the interaction between diet and diabetic predisposition for beta-cell function. A 4-day high-energy (HE) diet induced a 3-, 4-, and 1.5-fold increase in serum glucose, insulin, and triglycerides, respectively, in diabetes-prone (DP) but not diabetes-resistant (DR) P. obesus. Hyperglycemia and concurrent 90% depletion of islet immunoreactive insulin stores were partially corrected by an 18-h fast. In vitro early insulin response to glucose was blunted in both DR and DP perifused islets. The HE diet augmented early and late insulin response in DR islets, whereas in DP islets, secretion progressively declined. Dose-response studies showed a species-related increase in islet glucose sensitivity, further augmented in DP P. obesus by a HE diet, concomitant with a decreased threshold for glucose and a 55% reduction in maximal response. These changes were associated with a fourfold increase in glucose phosphorylation capacity in DP islets. There were no differences in islet glucokinase (GK) and hexokinase (HK) Km; however, GK Vmax was 3.7- to 4.6-fold higher in DP islets, and HK Vmax was augmented 3.7-fold by the HE diet in DP islets. We conclude that the insulin-resistant P. obesus has an inherent deficiency in insulin release. In the genetically predisposed P. obesus (DP), augmented islet glucose phosphorylation ability and diet-induced reduction of the glucose threshold for secretion may lead to inadequate insulin secretion and depletion of insulin stores in the presence of caloric abundance. Thus, genetic predisposition and beta-cell maladaptation to nutritional load seem to determine together the progression to overt diabetes in this species. It is hypothesized that similar events may occur in obese type 2 diabetic patients. |
| Databáze: | OpenAIRE |
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