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Effects of chronic calorie restriction or dietary resveratrol supplementation on insulin sensitivity markers in a primate, Microcebus murinus.

Marchal J, Blanc S, Epelbaum J, Aujard F, Pifferi F - PLoS ONE (2012)

Bottom Line: No differences were found after a 21-month period of treatment, except for lower glucose levels 30 min after glucose loading in CR animals.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.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.

View Article: PubMed Central - PubMed

Affiliation: Mécanismes Adaptatifs et Evolution, UMR 7179 Centre National de la Recherche Scientifique, Muséum National d'Histoire Naturelle, Brunoy, France.

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.

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Plasma glucose concentrations and area under curves (AUC) during oral glucose tolerance test in control (CTL), calorie restricted (CR) and resveratrol supplemented (RSV) animals.A: after 21 months of treatment and B: after 33 months of treatment. Data are expressed as means±SEM. Statistical significance (*) p<0.05 when comparing CTL and CR animals, ($) p<0.05 when comparing CTL and RSV animals.
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pone-0034289-g002: Plasma glucose concentrations and area under curves (AUC) during oral glucose tolerance test in control (CTL), calorie restricted (CR) and resveratrol supplemented (RSV) animals.A: after 21 months of treatment and B: after 33 months of treatment. Data are expressed as means±SEM. Statistical significance (*) p<0.05 when comparing CTL and CR animals, ($) p<0.05 when comparing CTL and RSV animals.

Mentions: The OGTT results are presented in Figure 2, for each treatment and by age group. OGTT measurements significantly varied according to the treatment (dF = 2/28, F = 6.926, p = 0.004), regardless of the duration of the treatment (dF = 1/28, F = 2.418, p = 0.131). Additionally, OGTT values varied within the time course (dF = 3/84, F = 39.68, p<0.001) according to the treatment (6/84, F = 5.74, p<0.001) and treatment duration (dF = 3/84, F = 3.61, p = 0.017). After 21 months of treatment, the CR and RSV animals presented slight decreases in glucose compared to the CTL animals, but neither was significant. However, after 33 months of treatment, post-hoc tests revealed that the CR animals presented lower plasma glucose levels at 30 and 60 minutes after the beginning of the OGTT (p = 0.012 and p = 0.041, respectively). The RSV animals presented lower glucose levels at 30 minutes after glucose loading (p = 0.043), while no significant difference was found 60 minutes after the glucose loading (p = 0.074). Additionally, baseline glucose levels were not different among the three groups at 21 or 33 months nor were glucose levels 120 minutes after the glucose loading.


Effects of chronic calorie restriction or dietary resveratrol supplementation on insulin sensitivity markers in a primate, Microcebus murinus.

Marchal J, Blanc S, Epelbaum J, Aujard F, Pifferi F - PLoS ONE (2012)

Plasma glucose concentrations and area under curves (AUC) during oral glucose tolerance test in control (CTL), calorie restricted (CR) and resveratrol supplemented (RSV) animals.A: after 21 months of treatment and B: after 33 months of treatment. Data are expressed as means±SEM. Statistical significance (*) p<0.05 when comparing CTL and CR animals, ($) p<0.05 when comparing CTL and RSV animals.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3316613&req=5

pone-0034289-g002: Plasma glucose concentrations and area under curves (AUC) during oral glucose tolerance test in control (CTL), calorie restricted (CR) and resveratrol supplemented (RSV) animals.A: after 21 months of treatment and B: after 33 months of treatment. Data are expressed as means±SEM. Statistical significance (*) p<0.05 when comparing CTL and CR animals, ($) p<0.05 when comparing CTL and RSV animals.
Mentions: The OGTT results are presented in Figure 2, for each treatment and by age group. OGTT measurements significantly varied according to the treatment (dF = 2/28, F = 6.926, p = 0.004), regardless of the duration of the treatment (dF = 1/28, F = 2.418, p = 0.131). Additionally, OGTT values varied within the time course (dF = 3/84, F = 39.68, p<0.001) according to the treatment (6/84, F = 5.74, p<0.001) and treatment duration (dF = 3/84, F = 3.61, p = 0.017). After 21 months of treatment, the CR and RSV animals presented slight decreases in glucose compared to the CTL animals, but neither was significant. However, after 33 months of treatment, post-hoc tests revealed that the CR animals presented lower plasma glucose levels at 30 and 60 minutes after the beginning of the OGTT (p = 0.012 and p = 0.041, respectively). The RSV animals presented lower glucose levels at 30 minutes after glucose loading (p = 0.043), while no significant difference was found 60 minutes after the glucose loading (p = 0.074). Additionally, baseline glucose levels were not different among the three groups at 21 or 33 months nor were glucose levels 120 minutes after the glucose loading.

Bottom Line: No differences were found after a 21-month period of treatment, except for lower glucose levels 30 min after glucose loading in CR animals.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.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.

View Article: PubMed Central - PubMed

Affiliation: Mécanismes Adaptatifs et Evolution, UMR 7179 Centre National de la Recherche Scientifique, Muséum National d'Histoire Naturelle, Brunoy, France.

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.

Show MeSH
Related in: MedlinePlus