Assessment of the Gluconeogenic Capabilities of Leptin-treated Diabetic Rats by Feeding Albumin and Fructose Diets

Abstract

The role of leptin in glucose homeostasis is not clearly defined. Chronic intracerebroventricular (ICV) leptin treatment in diabetic rats leads to a normalization of blood glucose. Additionally, short-term fasting of the same animals leads to a significant drop in blood glucose concentrations. However, when provided food ad libitum, leptin-treated rats regulate blood glucose levels at normal levels. Apparently, glucose from the diet helps to maintain glucose concentrations at normal physiological levels. In fasted animals not treated with leptin, gluconeogenesis and glycogenolysis maintain blood glucose levels in a normal physiological range. We propose that central leptin administration causes a reduction in hepatic glucose output, leading to the inability of the animals to maintain blood glucose concentrations during a fast. In this experiment, we used purified diets of albumin and fructose, which are known to be processed through gluconeogenesis to form glucose, to assess the gluconeogenic capability of leptin-treated rats. The inability of leptin-treated diabetic rats to use either precursor to successfully normalize fasted blood glucose levels suggests that gluconeogenesis is suppressed by leptin. The partial recovery of fructose toward normal blood glucose concentrations further suggests that the primary point of inhibition is through the repression of PEPCK. Additionally, lower stores of glycogen in leptin-treated diabetic rats after a fast suggest that leptin-treated rats are able to derive glucose from glycogen stores, but that these stores may be insufficient to maintain blood glucose concentrations during the fast.