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

Abstract

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.

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“…Gradual raise of mean fasting glucose level was observed in non vitamin D groups this might be due to glucose intolerance or inability to secrete insulin from pancreatic β cells due to lack of vitamin D since all the subjects in this group are state of vitamin D deficiency which is similar to our previous report 15 . On the contrary, subjects supplemented with vitamin D have not shown any improvement in the blood glucose reduction but the values are remained unvaried.…”

“…In view of the fact that ESR is a good predictor for the inflammatory response 21,22 moreover hsCRP is also significantly increased in non vitamin D group which can up regulate the expression of AT1 receptors and activate rennin angiotensin system (RAS) that could increase the arterial blood pressure this is probably due to vitamin D deficiency or inadequate sunlight exposure and utilization of vitamin D by the body cells because serum vitamin D is an important biological marker for regulating the hsCRP level in blood 17 and significant decrease of blood hsCRP was found in vitamin D supplemented group these changes might be due to anti obesity and anti inflammatory activity of vitamin D since obesity has a role in increase the CRP level in blood 15 these factors could also be a reason for the reduction of BMI in vitamin D group. At the same time disease activity is greatly reduced in this groups which might be due to anti inflammatory activity of vitamin D by controlling cytokines release and immune tolerance 23,24 .…”

Acute Reduction of Incretin Effect and Glucose Intolerance in Rats by Single Intragastric Administration of 3-deoxyglucosone

“…Actually, a single high-AGEs meal has been shown to affect glucose responses [22]. We recently have reported that glucose intolerance was not observed in normal rats 2 h after intravenous (i. v.) injection of 5 mg/kg 3DG [19]. In contrast, from the research of exogenous 3DG on plasma glucose in normal mice, we have observed that plasma glucose concentration was obviously increased 2 h after single oral administration of 5 mg/kg 3DG, supporting the hypothesis [20].…”

“…Therefore, early investigations have highlighted its potential role in the development of diabetic complications [16,17]. Recently, we have reported that abnormal elevation of circulating 3DG could participate in inducing IGT [18,19]. Apart from the further findings, exogenous 3DG has been reported to induce IGT in normal mice [20].…”

Accumulation of intestinal tissue 3-deoxyglucosone attenuated GLP-1 secretion and its insulinotropic effect in rats

“…In addition to intensively investigate as a precursor for AGEs, 3DG itself has certain biological activities [11–13], specifically on the ability to induce insulin resistance in vitro [13]. The further reports in clinical and animal research indicated that 3DG had been linked to an impaired glucose tolerance [6, 14, 15], thereby constituting an independent factor for the development of prediabetes.…”