3-Deoxyglucosone Induced Acute Glucose Intolerance in Sprague-Dawley Rats: Involvement of Insulin Resistance and Impaired beta-cell Function

摘要

A recent study found an increased level of 3DG during oral glucose load in healthy individuals, which redirects our attention to the effect of high plasma 3DG level in the pathophysiology of type 2 diabetes mellitus. We found previously that abnormally elevated plasma 3DG was significantly associated with the impaired glucose regulation in non-diabetic seniors. The current study aimed to investigate the acute effects of exogenous 3DG on plasma 3DG levels, glucose tolerance and insulin levels. A significant increase in the plasma level of 3DG was observed in rats administrated 50 mg/kg 3DG i.v. even 2 h after. With the acute elevation of circulating 3DG, intravenous glucose tolerance of normal rats was impaired, whereas plasma insulin levels were higher. The 3DG-mediated impairment in glucose tolerance was associated with the attenuated insulin-stimulated glucose uptake in the adipose and liver tissues and the decreased glucose-stimulated insulin secretion in the pancreas tissue. In rats treated with 50 mg/kg 3DG i.v., a reduced phosphorylation of p85-PI3K was observed in both the liver and pancreas tissues. The increase in plasma levels of 3DG and the deleterious effects of 3DG were attenuated by aminoguanidine pretreatment. Our results indicated a close association of 3DG with diabetes through participating in inducing acute glucose intolerance involvement of PI3K signaling in healthy individuals. By such a mechanism, a 3DG-targeted intervention to attenuation of the acute elevation of circulating 3DG is promising new therapeutic and prevention strategies for diabetes and its complications.