Reversibility of hyperglycaemia and islet abnormalities in the high fat-fed female ZDF rat model of type 2 diabetes

Effects of high-fat diet and fructose-rich diet on obesity, dyslipidemia and hyperglycemia in the WBN/Kob-<i>Lepr^fa</i> rat, a new model of type 2 diabetes mellitus

“…The main finding of this study was that a 4-week feeding of HFD and FRD resulted in a significant increase of body weights and visceral fat weights in WBKDF rats, indicating diet-induced visceral obesity. HFD-induced obesity in WBKDF rats was analogous to that in ZDF rats, one of the most well examined T2DM rats [19]. To our knowledge, this is the first study on FRD-induced obesity in rats with T2DM.…”

ER stress in rodent islets of Langerhans is concomitant with obesity and β-cell compensation but not with β-cell dysfunction and diabetes

“…12, 13, 14, 15, 19, 20, 29, 30, 31 This is supported by the results presented in this report showing that the expression levels of mRNAs implicated in β-cell function, growth and differentiation, such as Pdx1 , Ccnd1 (cyclin-D1), Slc2a2 (Glut2) and Gck (glucokinase), are increased in the islets of these rodent models of obesity (Figures 1 and 2), and, although we have not examined β-cell function or growth directly in this study, many other investigators have. For example, Goh et al demonstrated, using the two-step hyperglycaemic clamp method, that basal insulin secretion is elevated but glucose-stimulated insulin secretion (GSIS) in vivo is normal in both obese Zucker and female ZDF rats (fZDF).…”

“…29, 30, 31 In addition, increased β-cell mass in these animal models has been shown to be mediated, at least in part, by an increase in β-cell number and size. 13, 14, 19, 20 …”

“…11, 15 These animals do not develop diabetes unless they are placed on a high-fat diet (HFD), which results in decreased insulin sensitivity and a failure of the β-cell to adequately compensate, followed by a progressive decrease in β-cell function and mass. 11, 15, 18, 19, 20, 21 HFD-fed fZDFs (HF-fZDFs) have been proposed to be a good animal model of diet-induced T2DM. 18 Therefore, using ZO and fZDF rats as models of obesity and HF-fZDF rats as a model of diet-induced diabetes, we investigated whether there is a correlation between ER stress in the islets of Langerhans and (1) obesity and (2) HFD-induced diabetes.…”

Nrf2/antioxidant pathway mediates β cell self-repair after damage by high-fat diet–induced oxidative stress

“…In virtually all these lines of study, the β cell itself has been tacitly assumed to play the passive role of victim during its exposure to hyperglycemia. In some reports, oxidative stress caused by hyperglycemia has been suggested to be an operative mechanism in the continuation of β cell decline after the initiating (probably genetic) mechanism is triggered (22)(23)(24)(25)(26). We are unaware of any previous studies that directly address the hypothesis that, early in T2D, β cells spontaneously initiate an effort to repair themselves.…”