PPARα activation and increased dietary lipid oppose thyroid hormone signaling and rescue impaired glucose-stimulated insulin secretion in hyperthyroidism
| Autor: | Gemma K. Greenwood, Mary C. Sugden, Mark J. Holness, Nicholas D. Smith |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Thyroid Hormones
endocrine system medicine.medical_specialty endocrine system diseases Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Dietary lipid Biology Hyperthyroidism Eating Islets of Langerhans Antithyroid Agents Insulin-Secreting Cells Physiology (medical) Internal medicine Glucose Intolerance Insulin Secretion medicine Animals Insulin PPAR alpha Secretion Rats Wistar Insulin secretion Pancreatic hormone geography geography.geographical_feature_category Anticholesteremic Agents Thyroid Islet Dietary Fats Lipids Rats Glucose Pyrimidines medicine.anatomical_structure Endocrinology Starvation Female Insulin Resistance Signal transduction hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 295:E1380-E1389 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.90700.2008 |
| Popis: | The aim of the study was to investigate the impact of hyperthyroidism on the characteristics of the islet insulin secretory response to glucose, particularly the consequences of competition between thyroid hormone and peroxisome proliferator-activated receptor (PPAR)α in the regulation of islet adaptations to starvation and dietary lipid-induced insulin resistance. Rats maintained on standard (low-fat/high-carbohydrate) diet or high-fat/low-carbohydrate diet were rendered hyperthyroid (HT) by triiodothyronine (T3) administration (1 mg·kg body wt−1·day−1sc, 3 days). The PPARα agonist WY14643 (50 mg/kg body wt ip) was administered 24 h before sampling. Glucose-stimulated insulin secretion (GSIS) was assessed during hyperglycemic clamps or after acute glucose bolus injection in vivo and with step-up and step-down islet perifusions. Hyperthyroidism decreased the glucose responsiveness of GSIS, precluding sufficient enhancement of insulin secretion for the degree of insulin resistance, in rats fed either standard diet or high-fat diet. Hyperthyroidism partially opposed the starvation-induced increase in the glucose threshold for GSIS and decrease in glucose responsiveness. WY14643 administration restored glucose tolerance by enhancing GSIS in fed HT rats and relieved the impact of hyperthyroidism to partially oppose islet starvation adaptations. Competition between thyroid hormone receptor (TR) and PPARα influences the characteristics of GSIS, such that hyperthyroidism impairs GSIS while PPARα activation (and increased dietary lipid) opposes TR signaling and restores GSIS in the fed hyperthyroid state. Increased islet PPARα signaling and decreased TR signaling during starvation facilitates appropriate modification of islet function. |
| Databáze: | OpenAIRE |
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