Familial longevity is marked by enhanced insulin sensitivity

Aging Cell

Carolien A. Wijsman⁴  Maarten P. Rozing⁴  Trea C. M. Streefland¹  Saskia le Cessie²  Simon P. Mooijaart⁴  P. Eline Slagboom³  Rudi G. J. Westendorp⁴  Hanno Pijl¹  Diana van Heemst⁴ 

[1] Department of Endocrinology and Metabolic Disease, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, the Netherlands;Department of Medical Statistics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, the Netherlands;Section Molecular Epidemiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, the Netherlands;Department of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, the Netherlands

关键词: aging;    human;    hyperinsulinemic‐euglycemic clamp;    insulin sensitivity;    longevity;   

DOI  :  10.1111/j.1474-9726.2010.00650.x

来源: Wiley

【 摘 要 】

Summary

Insulin resistance is a risk factor for various age-related diseases. In the Leiden Longevity study, we recruited long-lived siblings and their offspring. Previously, we showed that, compared to controls, the offspring of long-lived siblings had a better glucose tolerance. Here, we compared groups of offspring from long-lived siblings and controls for the relation between insulin and glucose in nonfasted serum (n = 1848 subjects) and for quantitation of insulin action using a two-step hyperinsulinemic-euglycemic clamp (n = 24 subjects). Groups of offspring and controls were similar with regard to sex distribution, age, and body mass index. We observed a positive bi-phasic linear relationship between ln (insulin) levels and nonfasted glucose with a steeper slope from 10.7 mU L⁻¹ insulin onwards in controls compared to offspring (P = 0.02). During the clamp study, higher glucose infusion rate was required to maintain euglycemia during high-dose insulin infusion (P = 0.036) in offspring, reflecting higher whole-body insulin sensitivity. After adjustment for sex, age, and fat mass, the insulin-mediated glucose disposal rate (GDR) was higher in offspring than controls (42.5 ± 2.7 vs. 33.2 ± 2.7 μmol kg⁻¹ min⁻¹, mean ± SE, P = 0.025). The insulin-mediated suppression of endogenous glucose production and lipolysis did not differ between groups (all P > 0.05). Furthermore, GDR was significantly correlated with the mean age of death of the parents. In conclusion, offspring from long-lived siblings are marked by enhanced peripheral glucose disposal. Future research will focus on identifying the underlying biomolecular mechanisms, with the aim to promote health in old age.

【 授权许可】

Unknown   
© 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland