Abstract

Insulin is known to stimulate protein synthesis and mRNA, but its specific effects on growth hormone (GH) and prolactin (PRL) secretion have not been extensively studied. Insulin receptors on pituitary cells have been described in preliminary reports, and this proposal aims to study the in vitro regulation of PRL and GH release, synthesis and specific mRNA by insulin. Preliminary data demonstrates that insulin at physiological doses suppressed GH secretion and stimulates PRI secretion. The significance of the proposed project is that it will provide information on insulin action on polypeptide hormone synthesis and gene expression. These studies will provide insight into the etiology of elevated GH levels in uncontrolled diabetes. Patients with uncontrolled diabetes have elevated basal and exercise-induced GH levels, and GH has been implicated in the development of diabetic microvascular disease and retinopathy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK034824-03
Application #
3233100
Study Section
Metabolism Study Section (MET)
Project Start
1985-06-01
Project End
1988-05-31
Budget Start
1987-06-01
Budget End
1988-05-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048

  Publications

Webster, J; Prager, D; Melmed, S (1994) Insulin-like growth factor-1 activation of extracellular signal-related kinase-1 and -2 in growth hormone-secreting cells. Mol Endocrinol 8:539-44
Prager, D; Li, H L; Asa, S et al. (1994) Dominant negative inhibition of tumorigenesis in vivo by human insulin-like growth factor I receptor mutant. Proc Natl Acad Sci U S A 91:2181-5
Prager, D; Li, H L; Yamasaki, H et al. (1994) Human insulin-like growth factor I receptor internalization. Role of the juxtamembrane domain. J Biol Chem 269:11934-7
Prager, D; Yamasaki, H; Weber, M M et al. (1994) Role of the insulin-like growth factors in regulating neuroendocrine function. Neurobiol Aging 15:569-72
Yamamoto, H; Prager, D; Yamasaki, H et al. (1993) Rat pituitary GC cell insulin-like growth factor-I receptor regulation. Endocrinology 133:1420-5
Prager, D; Weber, M M; Gebremedhin, S et al. (1993) Interaction between insulin and thyroid hormone in rat pituitary tumour cells: insulin attenuates tri-iodothyronine-induced growth hormone mRNA levels. J Endocrinol 137:107-14
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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