The Influence of Dietary Restriction on the Development of Diabetes and Pancreatitis in Female WBN/Kob-Fatty Rats

Abstract

Abstract:Original WBN/Kob male rats commonly develop chronic pancreatitis by the age of 3 months, while diabetes mellitus occurs at 9 months. In contrast, female rats of this strain do not show pancreatitis or diabetes. The WBN/Kob-fatty rat is a homozygous (fa/fa) congenic strain for the fa allele of the leptin receptor gene (Lepr). In WBN/Kob-fatty rats, both females and males provide a model of non-insulin-dependent diabetes with obesity. The leptin receptor fatty gene (Lepr fa ) induces obesity and hyperphagia. In the present study, we examined the effect of dietary restriction on pancreatitis and diabetes in female WBN/Kob-fatty rats. Five female fatty rats comprised a restricted feeding group with paired-feeding from 3 to 13 weeks of age, and five female lean rats comprised a control group with paired-feeding. At 13 weeks of age, two of the five female fatty rats of the control group developed diabetes mellitus, while no female fatty rats of the restricted feeding group developed diabetes mellitus. At this stage, pathological changes of the pancreas were observed in female fatty rats. All female fatty rats showed severe interlobular, intra-lobular and intra-islet fibrosis. In female fatty rats of the restricted feeding group, pathological changes of the pancreas were milder those of the free-feeding fatty group. Although dietary restriction could not completely prevent pancreatitis in female fatty rats, the development of diabetes was inhibited by its reduction of the severity of pancreatitis.

Syphacia muris infection delays the onset of hyperglycemia in WBN/Kob-Lepr fa rats, a new type 2 diabetes mellitus model

“…Excessive caloric intake and consequent obesity cause insulin resistance and impaired pancreatic function (Di Marzo, 2008). Previous reports showed that dietary restriction inhibits the development of diabetes in fa/fa rats by reducing pancreatitis (Akimoto et al, 2010). In our study, however, S. muris infection has not affected the body weight, food and water intake, or the weights of examined organs.…”

Plasma Profiles of Glucose, Insulin and Lipids in the Male WBN/Kob-<i>Lepr^fa</i> Rat, a New Model of Type 2 Diabetes with Obesity

“…The fa/fa(WBN/Kob-Lepr fa ) rat, a new congenic strain derived by crossing ZF rats with lean rats, has been claimed to be a new model of T2D with obesity [1,2]. We have elucidated the plasma profiles of glucose, insulin and lipids to further characterize the pathophysiologic features of the fa/ fa rat as a T2D model in comparison with lean (the original WBN/Kob) rats.…”

“…Animal models of T2D are useful to elucidate the pathogenesis of the disease and to evaluate the therapeutic activity of new medications. The currently established rodent T2D models are divided into 2 broad categories: experimentally induced nonspontaneous models, and genetically induced spontaneous models.The WBN/Kob-Lepr fa (fa/fa) rat is a new congenic strain that has been developed by introducing the fa gene of the Zucker fatty (ZF) rat into the original WBN/Kob (lean) rat genome [1,2]. The male, but not female, lean rat is a hereditary model of diabetes mellitus and chronic pancreatitis [13,15].…”

“…The WBN/Kob-Lepr fa (fa/fa) rat is a new congenic strain that has been developed by introducing the fa gene of the Zucker fatty (ZF) rat into the original WBN/Kob (lean) rat genome [1,2]. The male, but not female, lean rat is a hereditary model of diabetes mellitus and chronic pancreatitis [13,15].…”

“…The leptin receptor fatty gene (Lepr fa ) is a recessive mutation which was reported as a cause of obesity in ZF rats which exhibit hyperphagia resulting from a deficiency of leptin receptor signaling followed by obesity, hyperinsulinemia and dyslipidemia [6,11,16]. The fa/fa rat has been reported as a model of T2D with obesity [1,2], but little is known about profiles of plasma insulin and lipids in this strain. In order to further characterize the fa/fa rat as a T2D model, we evaluated the plasma profiles of glucose, insulin and lipids in fa/fa rats in comparison with those in lean rats.…”