The insulin receptor was evaluated at different disease stages in the sand rat (Psammomys obesus), a model for nutrition-induced diabetes. Nondiabetic sand rats showed markedly low receptor number in liver compared with albino rats. Their receptor had an intact tyrosine kinase activity but a higher K. for ATP in the phosphorylation reaction of exogenous substrates. The initial effects of overeating (i.e., development of hyperinsulinemia without hyperglycemia) were associated in the sand rat with a dramatic decrease in in vitro and in vivo insulin-induced receptor tyrosine kinase activity in both liver and muscle. In muscle, this coincided with a decrease in receptor number and an increase in basal tyrosine kinase activity. Similar canges were observed upon development of hyperinsulinemia with hyperglycemia. Upon recovery from the diabetic state by diet restriction, the impaired receptor kinse activation was corrected. Complete restoration occurred only in animals that fully recovered from the diabetic state and became normoinLinemic. These observations indicate that loss and gain of receptor tyrosine kinase activity were dependent on insulin levels. Thus, overeating may lead to the development of hyperinsulinemia through ineffective extraction of excess insulin by the scarce liver receptors. Hyperinsulinemia, in turn, causes a reversible reduction in receptor kinase activity, leading to insulin resistance. This sequence of events may be relevant to diet-related changes in human non-insulin-dependent diabetes mellitus.The development of non-insulin-dependent diabetes mellitus (NIDDM) in the majority of patients occurs in parallel to weight gain (1). Overeating is initially followed by hyperinsulinemia and insulin resistance, which gradually develop into pronounced hyperglycemia. This diabetogenic process may be reversed by diet restriction and weight loss (2). Since both hyperinsulinemia and insulin resistance coincide with weight gain in humans, it is not feasible to determine which is the primary event mediating the effect of obesity. We have addressed this query in an animal model of NIDDM. The sand rat is a desert-adapted gerbil that in its natural habitat is nondiabetic (3-7). In captivity, on an ad libitum rodent diet, it develops obesity and hyperinsulinemia without or with hyperglycemia (6,7). Through control of the animals' diet, it is possible to discern several stages of development of glucose intolerance, as well as reverse them, thus addressing the sequence of events that lead to induction of diabetes. We studied the insulin receptor (IR) function in these wellcharacterized animals and found alterations that may be relevant to human nutrition-induced diabetes. ['t-32P]ATP was from Amersham. ATP, CTP, Hepes, Tween 20, poly(Glu8Tyr20), bovine serum albumin (insulin free), N-acetyl-D-glucosamine, leupeptin, aprotinin, soybean trypsin inhibitor, and phenylmethylsulfonyl fluoride were from Sigma. Wheat germ agglutinin (WGA) and Con A coupled to agarose were from Bio-Makor (Rehovot, Israel). Reagen...

No abstract

Higher PGLI values were associated with worse glycemic control and increased LVMI. Efforts should be made to minimize the PGL. All other risk factors that may contribute to the development of LVH in PD patients should be identified and treated. Additional multicenter, randomized control trials are needed to determine the target objectives of PGLI.

Objective: To evaluate the impact of the peritoneal glucose load (PGL) on hydration status and inflammation in peritoneal dialysis (PD) patients. Methods: This cross-sectional study evaluated stable PD patients using a novel PGL index (PGLI), which was calculated as the net glucose content (g) in the PD solutions administered in the daily PD prescription divided by the dry body weight (kg) assessed by whole-body bioimpedance spectroscopy. The relationship between PGLI and glycosylated haemoglobin (HbA 1c ), fluid overload (FO), and inflammatory markers was investigated. Results: A total of 43 stable PD patients participated in the study. Significant positive correlations were found between PGLI and HbA 1c , FO, plasma high sensitivity C-reactive protein (hsCRP), and plasma interleukin-6 (IL-6) levels. HbA 1c , FO, plasma hsCRP and plasma IL-6 levels were significantly higher in patients with PGLI >3 g/kg/day compared with those with PGLI 3 g/kg/day. Conclusions: PGLI values >3 g/kg/day may be associated with poor glycaemic control, over hydration and augmented inflammation. PGLI might be a useful tool for the quantitative assessment of the PGL and could be applied when managing PD patients.