Opening of ATP-sensitive Potassium Channel by Insulin in the Brain-induced Insulin Secretion in Wistar Rats

Abstract

Cerebral insulin can regulate glucose homeostasis via activation of the parasympathetic nervous system, which results in the reduction of hepatic glucose output. However, the precise mechanism(s) through which cerebral insulin directly exerts an effect on insulin secretion remains unclear. In the present study, we found that cerebral administration of insulin caused an increase of plasma insulin concentration and a concomitant decrease in plasma glucose levels within one hour. These effects were blocked by vagotomy or intraperitoneal injection of 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide, a specific M (3) antagonist. The mediating influence of parasympathetic activation can thus be considered. The adenosine triphosphate-sensitive potassium (K-ATP) channel is a key mediator of the cerebral action of insulin. The plasma glucose-lowering action of insulin was abolished by cerebral administration of glibenclamide or repaglinide at concentrations sufficient to block K-ATP channels. In conclusion, our findings suggest that cerebral insulin may induce insulin release by stimulating the opening of K-ATP channels, which in turn activate parasympathetic tone in pancreatic tissue.

Inhibition of Insulin Degrading Enzyme by Racecadotril in the Brain of Wistar Rats

“…As shown in • ▶ Fig. 6 , blood glucose level was not signifi cantly changed in rats that received subdiaphragmatic vagotomy as compared to the sham-operated group (p > 0.05); this is similar to a previous report [13] .…”

“…A plasma glucose lowering eff ect was observed in rats that received an i. v. injection of racecadotril (2 mg / kg). Intracerebroventricular administration of glibenclamide at a dose suffi cient to block central K ATP channels [13] abolished the racecadotrilinduced plasma glucose-lowering action ( • ▶ Fig. 5 ).…”

“…Activation of K ATP channels in hypothalamus is suffi cient to reduce plasma glucose through inhibition of hepatic gluconeogenesis [12] . A previous study showed that administration of insulin into the brain induces a signifi cant decrease in plasma glucose via opening of K ATP channels, which in turn activates parasympathetic tone in pancreatic tissue [13] . Also, racecadotril decreased blood glucose through an increase of cholinergic tone, which induces insulin secretion [9] .…”

Insulin’s direct hepatic effect explains the inhibition of glucose production caused by insulin secretion

“…In addition, while it has been shown that insulin secretion can be neurally controlled, the role of brain insulin action in causing this effect is uncertain (36). A pharmacologic dose of insulin injected into the lateral cerebral ventricle was shown to increase insulin secretion in dogs (57) and brain K ATP channel activation caused a similar effect in rats (58). Thus, brain insulin action may feed-forward to stimulate insulin secretion and thereby inhibit HGP.…”

Hypothalamic Control of Systemic Glucose Homeostasis: The Pancreas Connection

“…Regarding insulin, studies in dogs concluded that ventricular injection of this hormone stimulates pancreatic insulin secretion under constant baseline concentration of glucose [35]. Likewise, cerebral insulin causes a fast increase in plasma insulin and a concomitant decrease in glucose levels in rats via KATP channels [36]. However, other studies failed to confirm these findings [37, Ishihara 2009 #12091].…”