Roles of phospho-GSK-3β in myocardial protection afforded by activation of the mitochondrial K ATP channel.

The aim of this study was to determine the roles of glycogen synthase kinase-3β (GSK-3β) in cardioprotection by activation of the mitochondrial ATP-sensitive K(+) channel (mK(ATP) channel). In isolated rat hearts, an mK(ATP) activator, diazoxide, and a GSK-3β inhibitor, SB216763, similarly limited infarct size and the combination of these agents did not afford further protection. The protection by pre-ischemic treatment with diazoxide was abolished by inhibition of protein kinase C-ε (PKC-ε) or phosphatidylinositol-3-kinase (PI3K) upon reperfusion.

Angiotensin II type 1 receptor-mediated upregulation of calcineurin activity underlies impairment of cardioprotective signaling in diabetic hearts.

Rationale: The diabetic heart is resistant to ischemic preconditioning because of diabetes-associated impairment of phosphatidylinositol 3-kinase (PI3K)-Akt signaling. The mechanism by which PI3K-Akt signaling is impaired by diabetes remains unclear.

Objective: Here, we examined the hypothesis that phosphorylation of Jak2 upstream of PI3K is impaired in diabetic hearts by an angiotensin II type 1 (AT1) receptor-mediated mechanism.

Endoplasmic reticulum stress in diabetic hearts abolishes erythropoietin-induced myocardial protection by impairment of phospho-glycogen synthase kinase-3beta-mediated suppression of mitochondrial permeability transition.

Objective: Alteration in endoplasmic reticulum (ER) stress in diabetic hearts and its effect on cytoprotective signaling are unclear. Here, we examine the hypothesis that ER stress in diabetic hearts impairs phospho-glycogen synthase kinase (GSK)-3beta-mediated suppression of mitochondrial permeability transition pore (mPTP) opening, compromising myocardial response to cytoprotective signaling.

Research Design And Methods: A rat model of type 2 diabetes (OLETF) and its control (LETO) were treated with tauroursodeoxycholic acid (TUDCA) (100 mg .

Roles of Cx43-associated protein kinases in suppression of gap junction-mediated chemical coupling by ischemic preconditioning.

Ischemic preconditioning (PC) suppresses chemical coupling of cardiomyocytes via gap junctions (GJs) during ischemia, which is an adjunct mechanism of protection. The aim of this study was to characterize roles of protein kinases in PC-induced GJ modulation. In isolated rat hearts, ventricular tissues were sampled before and after ischemia with or without PC, and intercalated disc-rich fractions were separated for immunoprecipitation and immunoblotting.

Modulation of the mitochondrial permeability transition pore complex in GSK-3beta-mediated myocardial protection.

Recently we found that the level of anti-infarct tolerance afforded by ischemic preconditioning (IPC) and erythropoietin (EPO) infusion was closely correlated with the level of Ser9-phospho-GSK-3beta upon reperfusion in the heart. To get an insight into the mechanism by which phospho-GSK-3beta protects the myocardium from ischemia/reperfusion injury, we examined the effects of IPC and EPO on interactions between GSK-3beta and subunits of the mitochondrial permeability transition pore (mPTP) in this study. Rat hearts were subjected to 25-min global ischemia and 5-min reperfusion in vitro with or without IPC plus EPO infusion (5 units/ml) before ischemia.

Ghrelin differentially modulates glucose-induced insulin secretion according to feeding status in sheep.

The present study was conducted to investigate roles of ghrelin in glucose-induced insulin secretion in fasting- and meal-fed state in sheep. Castrated Suffolk rams were fed a maintenance diet of alfalfa hay cubes once a day. Hyperglycemic clamp (HGC) was carried out to examine glucose-induced insulin response from 48 to 53 h (fasting state) and from 3 to 8 h (meal-fed state) after feeding in Experiment 1 and 2 respectively.

Involvement of cholinergic neurons in the regulation of the ghrelin secretory response to feeding in sheep.

We previously demonstrated that a transient surge in plasma levels of ghrelin occurs just prior to a scheduled meal and that this surge is modified by the feeding regimen. This suggests that the ghrelin secretion is regulated by the autonomic nervous system, especially the cholinergic projections to the stomach. To test this hypothesis, we investigated changes in plasma ghrelin levels at feeding time in rams by administering cholinergic blockers (atropine and hexamethonium) and a cholinergic accelerator (metoclopramide).

A transient surge of ghrelin secretion before feeding is modified by different feeding regimens in sheep.

Ghrelin is a recently identified orexigenic hormone secreted by the stomach and has been implicated in meal-time hunger. Several experiments demonstrate a transient surge in ghrelin secretion shortly before a scheduled meal, suggesting from the involvement of cephalic mechanisms. If ghrelin secretion is stimulated by hunger in sheep, plasma levels of ghrelin should be modified by different feeding regimens that affect hunger drive.