Early Effects of Metabolic Syndrome on ATP-Sensitive Potassium Channels from Rat Pancreatic Beta Cells

Abstract

Metabolic syndrome (MS) is a cluster of metabolic signs that increases the risk of developing type 2 two diabetes mellitus and cardiovascular diseases. MS leads to pancreatic beta cell exhaustion and decreased insulin secretion through unknown mechanisms in a time-dependent manner. ATP-sensitive potassium channels (KATP channels), common targets of anti-diabetic drugs, participate in the glucose-stimulated insulin secretion, coupling the metabolic status and electrical activity of pancreatic beta cells. We investigated the early effects of MS on the conductance, ATP and glybenclamide sensitivity of the KATP channels. We used Wistar rats fed with a high-sucrose diet (HSD) for 8 weeks as a MS model. In excised membrane patches, control and HSD channels showed similar unitary conductance and ATP sensitivity pancreatic beta cells in their KATP channels. In contrast, MS produced variability in the sensitivity to glybenclamide of KATP channels. We observed two subpopulations of pancreatic beta cells, one with similar (Gly1) and one with increased (Gly2) glybenclamide sensitivity compared to the control group. This study shows that the early effects of MS produced by consuming high-sugar beverages can affect the pharmacological properties of KATP channels to one of the drugs used for diabetes treatment.

The reversible effects of free fatty acids on sulfonylurea-stimulated insulin secretion are related to the expression and dynamin-mediated endocytosis of KATP channels in pancreatic β cells

“…induced Metabolic syndrome (MS) model and control. In contrast, MS produced variability in the sensitivity to glybenclamide of K ATP channels [30]. Our study showed that OA and PA had the same effects on SUR1 and Kir6.2 expression and endocytosis together with changes with insulin secretion.…”

The effects of sucrose and arsenic on muscular insulin signaling pathways differ between the gastrocnemius and quadriceps muscles

“…Previously, we reported that a model of MS in Wistar rats consuming 20% sucrose through drinking water for 2 months developed central obesity, insulin resistance, cardiac arrhythmias, hypertriglyceridemia, and alterations in pancreatic beta-cells ( 27 – 30 ). Thus, we aimed to evaluate the alterations induced by sucrose and arsenic consumption in vivo on the canonical and proteolytic pathways that control insulin-stimulated GLUT4 translocation in the quadriceps and gastrocnemius muscles.…”