Short-term calorie restriction improves glucose homeostasis in old rats: involvement of AMPK.

The occurrence of metabolic disorders, such as diabetes, obesity, atherosclerosis, and hypertension, increases with age. Inappropriate food intake, when combined with genetic and hormonal factors, can trigger the occurrence of these diseases in aged organisms. This study investigated whether short-term calorie restriction (CR; 40% of the intake of control animals (CTL) for 21 days) benefits 1-year-old (CR1yr) and 2-year-old (CR2yr) Wistar rats, with regard to insulin secretion and action. Plasma insulin and the insulin secreted by isolated islets were measured with radioimmunoassay, and the insulin sensitivity of peripheral tissues was assessed with the intraperitoneal glucose tolerance test (IPGTT), intraperitoneal insulin tolerance test, and hepatic and muscle adenosine monophosphate-activated protein kinase (AMPK) phosphorylation measurements. Body weight, epididymal fat pad, epididymal fat pad/body weight index, plasma glucose, and insulin were lower in the CR1yr than in the control (CTL1yr) rats. Serum cholesterol, triglycerides, and protein, as well as hepatic and muscle glycogen content, were similar between the CR and CTL groups. The IPGTT was higher in CR2yr and CTL2yr rats than in CR1yr and CTL1yr rats, and insulin sensitivity was higher in CR1yr and CR2yr rats than in their respective CTLs. This was associated with an increase in hepatic and muscle AMPK phosphorylation. No differences in glucose-induced insulin secretion in the isolated islets were observed between CRs and their respective CTL rats. In conclusion, short-term calorie restriction provoked more severe alterations in CR1yr than CR2yr rats. The normoglycemia observed in both CR groups seems to be due to an increase in insulin sensitivity, with the involvement of liver and muscle AMPK.