Metabolic syndrome induces changes in K_ATP-channels and calcium currents in pancreatic β-cells

Abstract

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 β cells fail in DM2. Pancreatic β 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 β 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 β 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 β cells showed smaller calcium currents. These cells may represent a β cell subpopulation as it becomes exhausted by the long-term high sucrose diet.

Keywords: :

• insulin
• secretion
• hyperinsulinemia
• triglycerides
• hypertension
• diabetes
• calcium
• metabolic syndrome
• calcium channels
• insulin secretion
• K_ATP channels

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We are grateful to Alvaro Caso for reading and discussing the manuscript, to Felix Sierra for assistance in animal care and experiments, and to Ana Ma. Escalante and Francisco Pérez Eugenio from the Computer Unit, IFC, UNAM.

Grants

This work was supported by DGAPA-PAPIIT IN215611, Gobierno del Distrito Federal PICDS08–72 and CONACYT CB2009/131647.

Author’s Contributions

VM, CL, performed experiments, participated in design of the experiments, final version of the manuscript. AVR performed uric acid quantification, GRG participated in cholesterol and triglycerides quantification, MH conceived the study, designed experiments, coordination of participants, writing the manuscript. All authors read and approved the final manuscript.