期刊
ISLETS
卷 4, 期 4, 页码 302-311出版社
LANDES BIOSCIENCE
DOI: 10.4161/isl.21374
关键词
insulin; secretion; hyperinsulinemia; triglycerides; hypertension; diabetes; calcium; metabolic syndrome; calcium channels; insulin secretion; K-ATP channels
资金
- DGAPA-PAPIIT [IN215611]
- Gobierno del Distrito Federal [PICDS08-72]
- CONACYT [CB2009/131647]
Metabolic syndrome (MS) can be defined as a group of signs that increases the risk of developing type 2 diabetes mellitus (DM2). These signs include obesity, hyperinsulinemia and insulin resistance. We are interested in the mechanisms that trigger hyperinsulinemia as a step to understand how beta cells fail in DM2. Pancreatic beta cells secrete insulin in response to glucose variations in the extracellular medium. When they are chronically over-stimulated, hyperinsulinemia is observed; but then, with time, they become incapable of maintaining normal glucose levels, giving rise to DM2. A chronic high sucrose diet for two months induces MS in adult male Wistar rats. In the present article, we analyzed the effect of the internal environment of rats with MS, on the activity of ATP-sensitive potassium channels (K-ATP) and calcium currents of pancreatic beta cells. After 24 weeks of treatment with 20% sucrose in their drinking water, rats showed central obesity, hyperinsulinemia and insulin resistance, and their systolic blood pressure and triglycerides plasma levels increased. These signs indicate the onset of MS. K-ATP channels in isolated patches of beta cells from MS rats, had an increased sensitivity to ATP with respect to controls. Moreover, the macroscopic calcium currents, show increased variability compared with cells from control individuals. These results demonstrate that regardless of genetic background, a high sucrose diet leads to the development of MS. The observed changes in ionic channels can partially explain the increase in insulin secretion in MS rats. However, some beta cells showed smaller calcium currents. These cells may represent a beta cell subpopulation as it becomes exhausted by the long-term high sucrose diet.
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