Pancreatic islets from hypothalamic obese rats maintain K+ATP channel-dependent but not -independent pathways on glucose-induced insulin release process

Abstract

One of the main features of obesity is hyperinsulinemia, which is related to insulin oversecretion. Glucose is by far the major physiological stimulator of insulin secretion. Glucose promotes an increase in the ATP/ADP ratio, which inactivates ATP-sensitive K+ channels (K+ATP) and induces beta cell depolarization with consequent calcium influx. Increased intracellular calcium concentration triggers insulin exocytosis. K+ATP channel function is important for K+ATP channel-dependent pathways involved in glucose-stimulated insulin secretion (GSIS). However, K+ATP channel-independent pathway has been identified and it has been found that this pathway sustains GSIS. Both pathways are critical to better GSIS control. GSIS was studied in pancreatic islets from hyperinsulinemic adult obese rats obtained by monosodium L-glutamate (MSG) neonatal treatment. Islets from MSG-obese rats were more glucose responsive than control ones. Diazoxide, a drug which maintains the K+ATP channels open without interfering with cell metabolism, blocked GSIS in islets from both groups. High extracellular potassium concentration plus diazoxide was used to study an alternative to the K+ATP channel pathway; in these conditions islets from MSG-obese rats did not respond, while islets from control animals showed enhanced GSIS. Results indicate that MSG-obese rats oversecreted insulin, even though the K+ATP channel-independent pathway is impaired in their beta cells.