Comparisons of insulin and biosynthetic human proinsulin actions in cultured hepatocytes. Kinetics and biologic potencies

Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme
T P Ciaraldi, D Brady

Abstract

The binding and biologic potencies as well as kinetics of action of human biosynthetic proinsulin (HPro) were studied in primary cultures of rat hepatocytes. HPro had 3% (on a molar basis) of the potency of porcine insulin for displacing (125I)-TyrA14-insulin from receptors. Maximally effective concentrations of insulin and HPro caused similar stimulations of 14C-glucose incorporation into glycogen and glycogen synthase activity. However, the dose response curve for HPro stimulation of glycogen synthase was shifted far to the right (EC50 = 4.1 +/- 1.1 nM) of that for insulin (.09 +/- .01). The relative biologic potency of HPro was approximately 3%. Biologically equivalent maximal doses of insulin (8.3 nM) and HPro (53.2 nM) stimulated glycogen synthase activity with similar time courses; half maximal between 15-30 min with maximal effects at 60 min. Deactivation of glycogen synthase upon removal of the hormone was very rapid for both hormones. The relative binding and biologic potencies of HPro compared to insulin in liver (approximately 3%) were similar to values previously seen in adipocytes. This fact, together with the similarity of kinetics of action, suggest that the in vivo hepatoselectivity of HPro is not a property of ...Continue Reading

Citations

May 29, 2003·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Gerald F DaviesLalita A Bharadwaj
Apr 1, 1993·Journal of Diabetes and Its Complications·J S Yudkin
May 20, 2009·The Biochemical Journal·Lynley D PoundRichard M O'Brien
Jul 1, 1992·The American Journal of Physiology·S N DavisK G Alberti
Sep 1, 1991·Metabolism: Clinical and Experimental·S N DavisK G Alberti

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