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Intracerebroventricular Injection of Alarin Increased Glucose Uptake in Skeletal Muscle of Diabetic Rats.

ABSTRACT: In order to investigate the central effect of alarin on glucose uptake, we administered alarin and/ or its inhibitor, ala6-25Cys into the cerebral ventricles of the type 2 diabetic rats. Then the relative parameters about glucose uptake in skeletal muscles were measured. We found that central treatment with alarin significantly increased the food intake, body weight and glucose infusion rates in hyperinsulinemic euglycemic clamp tests of the animals. Besides, the treatment also enhanced 2-deoxy-[3H]-D-glucose uptake, vesicle-associated membrane protein 2 contents, glucose transporter 4 protein and mRNA expression, as well as pAktThr308, pAktSer473 and total Akt levels in muscle cells, but reduced plasma glucose and insulin levels of the rats. All of the alarin-inducing events may be antagonised by central injection of ala6-25Cys. These results suggest that central administration of alarin stimulates glucose uptake mediated by activation of Akt signal pathway in type 2 diabetic animals.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC4595443 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Intracerebroventricular Injection of Alarin Increased Glucose Uptake in Skeletal Muscle of Diabetic Rats.

Zhang Zhenwen Z Wu Yongkang Y Sheng Shudong S Guo Lili L He Biao B Fang Penghua P Shi Mingyi M Bo Ping P Zhu Yan Y

PloS one 20151006 10

In order to investigate the central effect of alarin on glucose uptake, we administered alarin and/ or its inhibitor, ala6-25Cys into the cerebral ventricles of the type 2 diabetic rats. Then the relative parameters about glucose uptake in skeletal muscles were measured. We found that central treatment with alarin significantly increased the food intake, body weight and glucose infusion rates in hyperinsulinemic euglycemic clamp tests of the animals. Besides, the treatment also enhanced 2-deoxy- ...[more]

PMID: 26439383

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Project description:BACKGROUND: Retinoid X receptor (RXR) ? is a nuclear receptor-type transcription factor expressed mostly in skeletal muscle, and regulated by nutritional conditions. Previously, we established transgenic mice overexpressing RXR? in skeletal muscle (RXR? mice), which showed lower blood glucose than the control mice. Here we investigated their glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: RXR? mice were subjected to glucose and insulin tolerance tests, and glucose transporter expression levels, hyperinsulinemic-euglycemic clamp and glucose uptake were analyzed. Microarray and bioinformatics analyses were done. The glucose tolerance test revealed higher glucose disposal in RXR? mice than in control mice, but insulin tolerance test revealed no difference in the insulin-induced hypoglycemic response. In the hyperinsulinemic-euglycemic clamp study, the basal glucose disposal rate was higher in RXR? mice than in control mice, indicating an insulin-independent increase in glucose uptake. There was no difference in the rate of glucose infusion needed to maintain euglycemia (glucose infusion rate) between the RXR? and control mice, which is consistent with the result of the insulin tolerance test. Skeletal muscle from RXR? mice showed increased Glut1 expression, with increased glucose uptake, in an insulin-independent manner. Moreover, we performed in vivo luciferase reporter analysis using Glut1 promoter (Glut1-Luc). Combination of RXR? and PPAR? resulted in an increase in Glut1-Luc activity in skeletal muscle in vivo. Microarray data showed that RXR? overexpression increased a diverse set of genes, including glucose metabolism genes, whose promoter contained putative PPAR-binding motifs. CONCLUSIONS/SIGNIFICANCE: Systemic glucose metabolism was increased in transgenic mice overexpressing RXR?. The enhanced glucose tolerance in RXR? mice may be mediated at least in part by increased Glut1 in skeletal muscle. These results show the importance of skeletal muscle gene regulation in systemic glucose metabolism. Increasing RXR? expression may be a novel therapeutic strategy against type 2 diabetes.

Dataset Information

Intracerebroventricular Injection of Alarin Increased Glucose Uptake in Skeletal Muscle of Diabetic Rats.

Publications

Intracerebroventricular Injection of Alarin Increased Glucose Uptake in Skeletal Muscle of Diabetic Rats.

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