In light of the fact that patients with newly diagnosed Type I and Type II diabetes have significantly elevated basal and exercise- induced growth hormone (GH) levels despite their hyperglycemia, this proposal aims to continue the study of the effects of insulin on in vitro GH gene expression. Insulin action will be studied on the regulation of basal and stimulated GH gene transcription, mRNA levels and protein synthesis. Specific regulatory sites for insulin action will also be identified on the transfected GH gene. Insulin binding and receptor occupancy will be correlated with biologic action of insulin on GH gene expression. Increased GH levels have been implicated in development of diabetic macrovascular and microvascular complications. The elevations of GH have also been implicated in the pathophysiology of metabolic disorder in diabetes. The studies proposed here will provide further insight into the molecular mechanism of insulin action at the level of specific polypeptide hormone gene regulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK034824-07
Application #
3233103
Study Section
Metabolism Study Section (MET)
Project Start
1985-06-01
Project End
1993-05-31
Budget Start
1991-06-01
Budget End
1992-05-31
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
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Ezzat, S; Ezrin, C; Yamashita, S et al. (1993) Recurrent acromegaly resulting from ectopic growth hormone gene expression by a metastatic pancreatic tumor. Cancer 71:66-70
Yamasaki, H; Prager, D; Melmed, S (1993) Structure-function of the human insulin-like growth factor-I receptor: a discordance of somatotroph internalization and signaling. Mol Endocrinol 7:681-5
Prager, D; Yamasaki, H; Weber, M M et al. (1992) Human insulin-like growth factor I receptor function in pituitary cells is suppressed by a dominant negative mutant. J Clin Invest 90:2117-22
Ezzat, S; Ren, S G; Braunstein, G D et al. (1992) Octreotide stimulates insulin-like growth factor-binding protein-1: a potential pituitary-independent mechanism for drug action. J Clin Endocrinol Metab 75:1459-63

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