Glucose Transporter Levels in Tissues of Spontaneously Diabetic Zucker fa/fa Rat (ZDF/drt) and Viable Yellow Mouse (Avy/a)

Abstract

We used antibodies to the fat/muscle glucose transporter (GLUT4) and the liver glucose transporter (GLUT2) to measure levels of these proteins in various tissues of two rodent models of non-insulin-dependent (type II) diabetes mellitus: the obese spontaneously diabetic male Zucker fa/fa rat (ZDF/drt) and the male viable yellow Avy/a obese diabetic mouse. The ZDF/drt strain generally develops overt diabetes associated with decreased plasma insulin levels. Depending on the age of the animals, the ZDF/drt rats can be arbitrarily segregated into age-matched obese, mildly diabetic (blood glucose less than 11 mM) and obese, and severely diabetic (blood glucose greater than 20 mM) groups. Avy/a mice are comparably hyperglycemic but unlike the ZDF/drt rats are severely hyperinsulinemic. In both groups of diabetic animals, GLUT4 in adipose tissue, heart, and skeletal muscle was reduced 25-55%, and GLUT2 in liver was increased 30-40%, relative to lean, age-matched controls. However, when the mildly diabetic ZDF/drt rats were compared to the lean controls, the only significant difference was a 25% reduction of GLUT4 in heart. Within all of the ZDF/drt rats (excluding the lean controls), GLUT2 in liver and GLUT4 in adipose tissue, heart, and skeletal muscle correlated significantly with glycemia. These data suggest that, in these two models of type II diabetes, glucose transporter levels in muscle, adipose tissue, and liver are regulated in a tissue-selective manner in response to changes in insulin and glucose. Furthermore, at least in the ZDF/drt rat, alterations in GLUT2 and/or GLUT4 protein levels appear not to be associated with obesity per se but appear to be secondary to the severely diabetic state.(ABSTRACT TRUNCATED AT 250 WORDS)

Cocoa-rich diet ameliorates hepatic insulin resistance by modulating insulin signaling and glucose homeostasis in Zucker diabetic fatty rats

“…In fact, we have recently demonstrated that a cocoa extract increased GLUT-2 levels and glucose uptake in insulin-resistant HepG2 cells [14]. In agreement with all of the above, comparable contents of hepatic GLUT-2 have been reported in mildly diabetic ZDF and ZL rats [46], whereas the transporter levels increased in ZDF rats fed with cocoa. Therefore, the increased GLUT-2 content could also contribute to the hypoglycemic effect and to improve the hepatic sensitivity to the hormone observed in ZDF-Co animals.…”

Signals Derived From Glucose Metabolism Are Required for Glucose Regulation of Pancreatic Islet GLUT2 mRNA and Protein

“…Filters were first washed at room temperature in TBS (20 mM Tris, pH 7.4, 150 mM NaCI), 0.1% Tween-20, and subsequently blocked in TBS/5% powdered skim milk/ 0.2% NP-40 for 45 min at 37°C. Polyclonal antiserum to COOH-terminal peptides of human GLUT2, previously shown to cross-react with rat GLUT2 (19), was diluted in the blocking solution at 1 (xg/ml and incubated overnight. After newly washing and blocking in the previously stated conditions, filters were incubated with 1:5000 dilution of peroxidase-conjugated goat anti-rabbit IgG (Sigma) during 1 h. GLUT2 protein bands were visualized on autoradiographies with a chemiluminiscent reagent detection system (ECL, Amersham, UK).…”

DHEA-PC Slows the Progression of Type 2 Diabetes (Non–Insulin-Dependent Diabetes Mellitus) in the ZDF/Gmi-fa/fa Rat

“…2) levels increased during maturation, beginning at 6-7 weeks in this rat strain, is consistent with the observations of other investigators. 2,5 The hyperglycemia and hypertriglyceridemia observed in this strain may result from hyperphagia, which is a common trait. 14,28 Increased food intake, although not necessary for obesity, does increase the magnitude of the condition.…”

“…1,2 They become hyperglycemic and hypertriglyceridemic as diabetes advances between 7 and 12 weeks of age, and then plateau. [3][4][5] Their diets consist of high fat (6%) content food, 1,5 and their level of physical activity is low. They therefore may adequately resemble their human diabetic counterpart.…”