Effects of Chronic Calorie Restriction or Dietary Resveratrol Supplementation on Insulin Sensitivity Markers in a Primate, Microcebus murinus

Abstract

The prevalence of diabetes and hyperinsulinemia increases with age, inducing metabolic failure and limiting lifespan. Calorie restriction (CR) without malnutrition delays the aging process, but its long-term application to humans seems difficult. Resveratrol (RSV), a dietary polyphenol, appears to be a promising CR mimetic that can be easily administered in humans. In this work, we hypothesized that both CR and RSV impact insulin sensitivity in a non-human primate compared to standard-fed control (CTL) animals. Four- to five-year-old male grey mouse lemurs (Microcebus murinus) were assigned to three dietary groups: a CTL group, a CR group receiving 30% fewer calories than the CTL and a RSV group receiving the CTL diet supplemented with RSV (200 mg·day−1·kg−1). Insulin sensitivity and glycemia were assessed using an oral glucose tolerance test (OGTT) and the homeostasis model assessment of insulin resistance (HOMA-IR index) evaluation after 21 or 33 months of chronic treatment. Resting metabolic rate was also measured to assess the potential relationships between this energy expenditure parameter and insulin sensitivity markers. No differences were found after a 21-month period of treatment, except for lower glucose levels 30 min after glucose loading in CR animals. After 33 months, CR and RSV decreased glycemia after the oral glucose loading without decreasing fasting blood insulin. A general effect of treatment was observed on the HOMA-IR index, with an 81% reduction in CR animals and 53% in RSV animals after 33 months of treatment compared to CTL. Chronic CR and dietary supplementation with RSV affected insulin sensitivity by improving the glucose tolerance of animals without disturbing their baseline insulin secretion. These results suggest that both CR and RSV have beneficial effects on metabolic alterations, although these effects are different in amplitude between the two anti-aging treatments and potentially rely on different metabolic changes.

The anorexic effect of Ex4/Fc through GLP-1 receptor activation in high-fat diet fed mice

“…This explanation is, at least in part, supported by other recent studies that demonstrated that a chronic calorie restriction (e.g. animals receiving 70% calorie of the control) significantly improved insulin sensitivity and glucose tolerance without obvious changes in the body weight of the experimental animals [21]. Nevertheless, our previous studies along with the in vitro and in vivo evidence suggested that the therapeutic effects of Ex4/Fc are through GLP-1R signaling pathway.…”

Modulation of SIRT1-Foxo1 Signaling axis by Resveratrol: Implications in Skeletal Muscle Aging and Insulin Resistance

“…This speculation is supported by a recent study showing that neither resveratrol nor over-expression of SIRT1 enhanced the contents of cellular ATP and mitochondrial DNA in C2C12 cultures treated with AMPK-shRNA, an observation mimicked by pharmacological blockade of SIRT1 with EX527, implying that AMPK may act upstream of SIRT1 [60]. While the mechanisms underlying the finding that a 33-month resveratrol supplementation reduces the HOMA insulin resistance index without affecting body mass remains unclear [61], activation of AMPK by resveratrol may increase the enzymatic activity of SIRT1 to deacetylate and repress the hyperglycemic effects of Foxo1 and enhance the PGC-1α-related transcription cascade leading to improved mitochondrial metabolism (Fig. 2 & 3).…”

Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemicals: Focus on the Nervous System

“…Resveratrol treatment ameliorates abnormal insulin secretion and morphologic changes of pancreatic b cells in mice fed a high-fat diet and improves insulin resistance in rats fed fructose and in mice on a high-calorie diet (Baur et al, 2006;Bagul et al, 2012;Zhang et al, 2012a). A recent study showed that dietary supplementation with resveratrol increases insulin sensitivity and improves glucose tolerance in a nonhuman primate, the gray mouse lemur (Microcebus murinus) (Marchal et al, 2012). Curcumin treatment was evaluated in mice fed a highfat diet and was shown to prevent insulin resistance and obesity by attenuating lipogenic gene expression in the liver and inflammatory responses in adipose tissue (Shao et al, 2012).…”