Caloric restriction in obese pre-diabetic rats prevents beta-cell depletion, loss of beta-cell GLUT 2 and glucose incompetence

Abstract

Pre-diabetic male Zucker diabetic fatty rats (ZDF) become diabetic between 8 and 10 weeks of age. At that time their beta cells exhibit high basal insulin secretion, absent insulin response to glucose and loss of GLUT 2 glucose transporter. Beta-cell volume, which is increased at the onset of non-insulin-dependent diabetes, declines precipitously by age 18 weeks. To determine if expression of this diabetic phenotype was dependent upon the increased food intake of these rats, they were diet-matched to lean littermates for 12 weeks beginning at 6 weeks of age. Untreated control ZDF rats received an unrestricted diet for 3 months. All of the controls became hyperglycaemic by 8 weeks of age, whereas all diet-matched rats remained euglycaemic throughout the 3 months, despite the fact that at 18 weeks of age their mean body weight equaled that of obese rats on an unrestricted diet. In the former rats glucose-stimulated insulin secretion was absent at 12 weeks of age and GLUT-2-positive beta cells had fallen below 30%. The volume fraction of their beta cells was 2.6 times normal at this age but by 18 weeks of age it had declined by 75%. Diet restriction for 3 months prevented the loss of glucose-stimulated insulin secretion and the reduction of beta-cell GLUT-2 and beta-cell volume fraction. However, neither the elevated basal insulin secretion nor the exaggerated arginine-stimulated insulin secretion of the obese rats was reversed or prevented by caloric restriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes and apoptosis: lipotoxicity

“…Despite the increase in lipids, apoptosis is not discerned in these exocrine cells, perhaps because the lipids are in droplets of neutral fat. In b-cells, by contrast, lipid droplets are few and apoptosis is far more common [96] lived; they then lose glucose transporter-2 and glucokinase [52], which attenuates their glucose responsiveness, and overt diabetes sets in. Of note, ceramide has been reported to inhibit glucokinase [53].…”

Dietary restriction preserves the mass and function of pancreatic β cells via cell kinetic regulation and suppression of oxidative/ER stress in diabetic mice

“…Therefore, it seems possible that alimentary therapy may contribute to increased in vivo glucose uptake by these tissues. Furthermore, the preventive effect of dietary restriction upon β-cell depletion in obese prediabetic Zucker Diabetic Fatty (ZDF) rats also has been reported [16]. Furthermore, long-term dietary restriction reduces several risk factors for cardiovascular disease including dyslipidemia, hypertension abdominal obesity and insulin resistance [17].…”

Attenuation of type 2 diabetes mellitus in the male Zucker diabetic fatty rat: the effects of stress and non-volitional exercise

“…In rodent models, energy restriction [11,12], a reduction in fat mass [13], and increased exercise [14][15][16][17] improve insulin sensitivity and attenuate the development of T2DM. These interventions, which increase insulin action or sensitivity, are thought to result in a decreased demand for insulin and thus attenuate beta cell exhaustion.…”