Diabetes, Vol 43, Issue 4 546-551, Copyright © 1994 by American Diabetes Association

ARTICLES

Regulation of human insulin gene transcription by glucose, epinephrine, and somatostatin

JB Redmon, HC Towle and RP Robertson
Department of Medicine, University of Minnesota Medical School, Minneapolis.

We observed in the HIT cell, a clonal insulin-secreting cell line, that epinephrine and somatostatin lower insulin mRNA levels and intracellular insulin content in addition to the well-recognized effect of these hormones to inhibit insulin secretion. To determine whether these inhibitory hormones might regulate insulin synthesis at the level of insulin gene transcription, we studied HIT cell expression of a human insulin-chloramphenicol acetyl transferase (CAT) reporter gene in the presence of glucose, epinephrine, and somatostatin. HIT cell expression of this human insulin-CAT reporter gene was responsive to glucose in a concentration-dependent manner, increasing threefold as the glucose concentration increased from 0.4 to 11 mM. Epinephrine significantly inhibited insulin-CAT reporter gene expression (61 +/- 5% of control), an effect mediated specifically by the human insulin gene promoter/enhancer sequence. Somatostatin significantly inhibited expression of the human insulin-CAT reporter gene (65 +/- 4% of control) and, to a lesser extent, expression of a control reporter gene, pRSVCAT (78 +/- 4% of control). Thus, somatostatin may inhibit insulin gene transcription by insulin gene-specific effects as well as more general effects on gene expression. Both epinephrine and somatostatin inhibited expression of the human insulin-CAT reporter gene in a concentration-dependent manner that paralleled inhibition of insulin secretion. These studies indicate that epinephrine and somatostatin lower HIT cell insulin mRNA levels in part by inhibiting insulin gene transcription. Thus, hormonal inhibition of insulin secretion may be coupled with inhibition of insulin synthesis, thereby allowing the beta-cell to match insulin supply to secretory demand.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Khoo, S. C. Griffen, Y. Xia, R. J. Baer, M. S. German, and M. H. Cobb Regulation of Insulin Gene Transcription by ERK1 and ERK2 in Pancreatic {beta} Cells J. Biol. Chem., August 29, 2003; 278(35): 32969 - 32977. [Abstract] [Full Text] [PDF]

				M. C. Lawrence, H. S. Bhatt, and R. A. Easom NFAT Regulates Insulin Gene Promoter Activity in Response to Synergistic Pathways Induced by Glucose and Glucagon-Like Peptide-1 Diabetes, March 1, 2002; 51(3): 691 - 698. [Abstract] [Full Text] [PDF]

				B. Leibiger, T. Moede, T. Schwarz, G. R. Brown, M. Kohler, I. B. Leibiger, and P.-O. Berggren Short-term regulation of insulin gene transcription by glucose PNAS, August 4, 1998; 95(16): 9307 - 9312. [Abstract] [Full Text] [PDF]

				L. M. de Vargas, J. Sobolewski, R. Siegel, and L. G. Moss Individual beta  Cells within the Intact Islet Differentially Respond to Glucose J. Biol. Chem., October 17, 1997; 272(42): 26573 - 26577. [Abstract] [Full Text] [PDF]