Impairment of insulin-stimulated GLUT4 translocation in skeletal muscle and adipose tissue in the Tsumura Suzuki obese diabetic mouse: a new genetic animal model of type 2 diabetes

Abstract

Background: In skeletal muscle and adipocytes, insulin-stimulated glucose transport has been known to occur through the translocation of glucose transporter (GLUT) 4 from the intracellular pool to the plasma membrane. The Tsumura Suzuki obese diabetic (TSOD) mouse, a new genetic animal model of type 2 diabetes, develops moderate degrees of obesity and diabetes that are especially apparent in animals more than 11 weeks old. A defect in insulin stimulation of GLUT4 translocation also contributes to the characteristics of type 2 diabetes. Objective: To characterize this mouse further, we examined the alteration in insulin-stimulated GLUT4 translocation in the skeletal muscle and adipose tissue. Methods: For glucose and insulin tolerance tests, the mice were given glucose or insulin and blood samples were collected. After isolation of low-density microsomal membrane and plasma membrane from skeletal muscle and adipose tissue, insulin-stimulated translocation of GLUT4 in these TSOD mice was examined by Western blot. Results and Conclusions: TSOD mice showed a significant increase in blood glucose after the glucose load, and exhibited a significantly attenuated decrease in blood glucose concentrations after administration of insulin, compared with that in control Tsumura Suzuki non-obese (TSNO) mice. The insulinstimulated translocation of GLUT4 from low-density microsomal membranes to plasma membrane was significantly reduced in both skeletal muscle and adipose tissue of TSOD mice. These results indicate that the reduced insulin sensitivity in diabetic TSOD mice is presumably due, at least in part, to the impaired GLUT4 translocation by insulin in both skeletal muscle and adipocytes.

Diabetic Complications in a New Animal Model (TSOD mouse) of Spontaneous NIDDM with Obesity

“…The TSOD mouse showed spontaneous obesity, glucosurea, hyperglycemia, and hyperinsulinemia only in male mice [25]. Miura et al reported that the insulin-stimulated translocation of glucose transporter (GLUT) 4 from low-density microsomal membranes to plasma membrane was reduced in both skeletal muscle and adipose tissue of TSOD mice, and that the reduced insulin sensitivity was presumably due to this impaired GLUT4 translocation in both skeletal muscles and adipocytes [15]. Using a whole genome scan of quantitative trait loci affecting body weight, blood glucose and insulin concentrations, Hirayama et al identified four major loci of the TSOD mouse meeting the rigorous criteria for linkage [11].…”

Spontaneous onset of nonalcoholic steatohepatitis and hepatocellular carcinoma in a mouse model of metabolic syndrome

“…10,11 Tsumura Suzuki obese diabetes (TSOD) mice are novel polygenic models of spontaneous type-2 diabetes mellitus that develop moderate degrees of obesity, especially apparent in animals more than 11 weeks of age. 12,13 Unlike MSG mice, male TSOD mice showed glycosuria, hyperglycemia, and hyperinsulinemia without any special treatments. 14 In addition, the pathological characteristics of these mice were also examined under severe circumstances because steatohepatitis and liver nodules were frequently observed in male TSOD mice during preliminary examination.…”

A Study of Cardiovascular Function in Tsumura Suzuki Obese Diabetes, a New Model Mouse of Type 2 Diabetes

“…Furthermore, TSOD mice have several features similar to the pathologic condition and diabetic complications of human diabetes Type 2, including visceral fat accumulation, glucose tolerance, insulin tolerance, hypertension and peripheral neuropathy. 11,12,19) However, since TSOD mice had no deterioration of cardiac function except low R wave amplitude and myocardial damage in pathologic findings, despite their advanced age of 18 months, it seems that there was no onset of heart failure with diabetes (Figs. 2, 3, 4C).…”

“…10,11) Miura et al reported that the insulin-stimulated translocation of glucose transporter (GLUT) 4 from low-density microsomal membranes to the plasma membrane was significantly reduced in both skeletal muscle and adipose tissue of TSOD mice, and that reduced insulin sensitivity was presumably due to this impaired GLUT4 translocation in both skeletal muscles and adipocytes. 12) Hirayama et al identified three major loci meeting the rigorous criteria for linkage using a whole-genome scan of quantitative trait loci affecting body weight, blood glucose and insulin concentration. 13) However, no report has investigated the cardiovascular functions of TSOD mice.…”