Diabetes, Vol 37, Issue 2 160-165, Copyright © 1988 by American Diabetes Association

ARTICLES

Insulin biosynthesis in HIT cells. Effects of glucose, forskolin, IBMX, and dexamethasone

G Gold, RL Qian and GM Grodsky
Metabolic Research Unit, University of California, San Francisco 94143.

Glucose, forskolin, 3-isobutyl-1-methylxanthine (IBMX), and dexamethasone were tested as regulators of proinsulin biosynthesis in HIT T-15 cells, which are glucose-responsive simian virus 40-transformed hamster beta-cells. Rate of [3H]leucine incorporation into proinsulin was increased as glucose concentrations were raised from 0 to 20 mM. Biosynthetic rate increases were significant after 48 but not at 4 or 24 h of glucose and were greater for proinsulin than for total extractable proteins. After 48 h, glucose-stimulated proinsulin biosynthesis was unaffected by 10(-6) M forskolin and/or 3 x 10(-5) M IBMX but was specifically and significantly inhibited by 10(-6) M dexamethasone. Four hours of exposure to dexamethasone had no effect. When cells were incubated for 24 h and then continuously labeled for an additional 24 h, cellular conversion of labeled proinsulin to insulin was increased by glucose, and this increase was reversed or inhibited by 10(-6) M dexamethasone. Therefore, proinsulin biosynthesis in transformed HIT T-15 cells is regulated in several ways by metabolites and hormones in a manner that compares with biosynthetic regulation in normal beta-cells.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. L. Larsen Pancreas Transplantation: Indications and Consequences Endocr. Rev., December 1, 2004; 25(6): 919 - 946. [Abstract] [Full Text] [PDF]

				R. P. Robertson Islet Transplantation as a Treatment for Diabetes -- A Work in Progress N. Engl. J. Med., February 12, 2004; 350(7): 694 - 705. [Full Text] [PDF]