Telomerase deficiency impairs glucose metabolism and insulin secretion.
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.
Kuhlow
Doreen
D
Department of Human Nutrition, Inst. of Nutrition, University of Jena, Germany.
Florian
Simone
S
von Figura
Guido
G
Weimer
Sandra
S
Schulz
Nadja
N
Petzke
Klaus J
KJ
Zarse
Kim
K
Pfeiffer
Andreas F H
AF
Rudolph
K Lenhard
KL
Ristow
Michael
M
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001823:Body Composition / Q000235:genetics; D002245:Carbon Dioxide / Q000378:metabolism; D049109:Cell Proliferation; D004734:Energy Metabolism / Q000235:genetics; D018149:Glucose Intolerance / Q000235:genetics*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000473:pathology; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008055:Lipids / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D012313:RNA / Q000235:genetics; D019098:Telomerase / Q000172:deficiency* / Q000235:genetics; D016615:Telomere / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; C422952:telomerase RNA; D002245:Carbon Dioxide; D012313:RNA; D019098:Telomerase