Use of an in Vivo Model System to Investigate Niddm

Egan, J.

Abstract

We have been investigating the use of an in vivo model system, to study potential agents for use in non-insulin requiring diabetes mellitus (NIDDM). Dr. B. Hansen, University of Maryland, has an extraordinary well characterized rhesus monkey model of this disease. We therefore gave two peptides, GIP and GLP, both known to have insulinotropic effects in other systems, to these monkeys. We ascertained the dose required to give half maximum insulinotropic effects. We showed that even the NIDDM monkeys can get an insulinotropic effect if given enough of these agents. We showed the glucose threshold required for insulin release by GLP. Further studies are planned using combinations of these peptides.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute on Aging (NIA)
• Type: Intramural Research (Z01)
• Project #: 1Z01AG000214-02
• Application #: 3789775
• Support Year: 2
• Fiscal Year: 1992

Institution

• Name: National Institute on Aging
• Country: United States

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