Abstract

Aging is associated with an increased incidence of Type 11 diabetes mellitus. On looking at the characteristics of the age-related decline in insulin secretion that occurs with aging, it appears that the abnormality in insulin secretion that occurs in diabetes is an exaggeration of normal aging processes, coupled with increasing demand for insulin release in the setting of insulin resistance. Of great interest is the new information tha these changes can be reversed. We treated young (6 months) and old (23 months) Wistar rats with an infusion of human recombinant GLP-1 (1.5 pmol per kg body weight per minute) using an ALZET osmotic pump (1003D) implanted subcutaneously in the neck for 48 hours. Insulin mRNA was increased 3 fold in the GLP-1 infused animals. Even the old rats, which have a lower amount of mRNA (50% lower) for insulin than young rats, had a 3 fold increase in insulin mRNA. The abnormality in the insulin secretion with aging was also normalized by this treatment. Of great interest is the fact that beta cells can be induced to proliferate and perhaps new beta cells can be derived from precursor cells by stimulation with GLP-1.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000214-05
Application #
2333496
Study Section
Special Emphasis Panel (LCP)
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1996
Total Cost
Indirect Cost

  Institution

Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Carlson, Olga D; David, Jehan D; Schrieder, Jessica M et al. (2007) Contribution of nonesterified fatty acids to insulin resistance in the elderly with normal fasting but diabetic 2-hour postchallenge plasma glucose levels: the Baltimore Longitudinal Study of Aging. Metabolism 56:1444-51
Doyle, Maire E; Egan, Josephine M (2007) Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther 113:546-93
Mager, Donald E; Abernethy, Darrell R; Egan, Josephine M et al. (2004) Exendin-4 pharmacodynamics: insights from the hyperglycemic clamp technique. J Pharmacol Exp Ther 311:830-5
Meneilly, Graydon S; Greig, Nigel; Tildesley, Hugh et al. (2003) Effects of 3 months of continuous subcutaneous administration of glucagon-like peptide 1 in elderly patients with type 2 diabetes. Diabetes Care 26:2835-41
Elahi, Dariush; Muller, Denis C; Egan, Josephine M et al. (2002) Glucose tolerance, glucose utilization and insulin secretion in ageing. Novartis Found Symp 242:222-42; discussion 242-6
Egan, Josephine M; Meneilly, Graydon S; Habener, Joel F et al. (2002) Glucagon-like peptide-1 augments insulin-mediated glucose uptake in the obese state. J Clin Endocrinol Metab 87:3768-73
Zhou, Jie; Pineyro, Marco A; Wang, Xiaolin et al. (2002) Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors. J Cell Physiol 192:304-14
Korosi, J; McIntosh, C H; Pederson, R A et al. (2001) Effect of aging and diabetes on the enteroinsular axis. J Gerontol A Biol Sci Med Sci 56:M575-9
Vila Petroff, M G; Egan, J M; Wang, X et al. (2001) Glucagon-like peptide-1 increases cAMP but fails to augment contraction in adult rat cardiac myocytes. Circ Res 89:445-52
Wang, X; Zhou, J; Doyle, M E et al. (2001) Glucagon-like peptide-1 causes pancreatic duodenal homeobox-1 protein translocation from the cytoplasm to the nucleus of pancreatic beta-cells by a cyclic adenosine monophosphate/protein kinase A-dependent mechanism. Endocrinology 142:1820-7

Showing the most recent 10 out of 14 publications