Research Paper|Volume 2, Issue 10|pp 650—658

Telomerase deficiency impairs glucose metabolism and insulin secretion

Doreen Kuhlow^1,², Simone Florian³, Guido von Figura^4,⁵, Sandra Weimer², Nadja Schulz⁶, Klaus J. Petzke⁷, Kim Zarse¹, Andreas F.H Pfeiffer^2,⁸, K. Lenhard Rudolph^4,⁹, Michael Ristow^1,²

¹Department of Human Nutrition, Inst. of Nutrition, University of Jena, Jena, D-07743, Germany
²Department. of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, D-14558, Germany
³Department of Nutritional Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, D-14558, Germany
⁴Department of Molecular Medicine, University of Ulm, Ulm, D-89081, Germany
⁵Department of Internal Medicine I, University of Ulm, Ulm, D-89081, Germany
⁶Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, D-14558, Germany
⁷Stable Isotope Group, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, D-14558, Germany
⁸Department of Endocrinology, Diabetes and Nutrition, Charité University Medicine, CBF, Berlin, D-12203, Germany
⁹Max-Planck-Research Group on Stem Cell Aging, University of Ulm, Ulm, D-89081, Germany

Received: August 23, 2010Accepted: September 12, 2010Published: September 14, 2010

https://doi.org/10.18632/aging.100200

Copyright: © 2010 Kuhlow et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Reduced telomere length and impaired telomerase activity have been linked to several diseases associated with senescence and aging. However, a causal link to metabolic disorders and in particular diabetes mellitus is pending. We here show that young adult mice which are deficient for the Terc subunit of telomerase exhibit impaired glucose tolerance. This is caused by impaired glucose-stimulated insulin secretion (GSIS) from pancreatic islets, while body fat content, energy expenditure and insulin sensitivity were found to be unaltered. The impaired secretion capacity for insulin is due to reduced islet size which is linked to an impaired replication capacity of insulin-producing beta-cells in Terc-deficient mice. Taken together, telomerase deficiency and hence short telomeres impair replicative capacity of pancreatic beta-cells to cause impaired insulin secretion and glucose intolerance, mechanistically defining diabetes mellitus as an aging-associated disorder.