Chapter category: Endocrine

Control of Protein Synthesis by Insulin

This chapter appears in the following book:

Mechanisms of Insulin Action

Edited by: Alan R. Saltiel and Jeffrey E. Pessin
ISBN: 978-0-387-72203-0
» Get more information about this book at landesbioscience.com «

Chapter authors:
Joseph F. Christian and John C. Lawrence, Jr.

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The stimulation of protein synthesis is a classic action of insulin. Loss of the stimulatory effect of insulin on protein synthesis contributes to the cessation of growth and weight loss, which are hallmarks of untreated Type 1 diabetes mellitus. The effect of insulin on protein metabolism is complex and involves changes in both synthesis and degradation. In some cell types an increase in rate of protein synthesis may be detected within minutes of insulin treatment. This response to insulin occurs within a timeframe comparable to that of other acute actions of the hormone, such as the activation of glucose transport and glycogen synthase activation. The rapid effects of insulin on protein synthesis involve increases in mRNA translation, the process through which the genetic code transcribed in the mRNA template is translated into protein. Translation takes place on ribosomes in a complex series of reactions that can be segregated into three phases— initiation, elongation and termination. Each phase involves a select group of translation factors, referred to as initiation factors, elongation factors, and release factors (abbreviated eIF, eEF, and eRF, respectively; where “e” is eukaryotic). Although the effects of insulin on mRNA translation have received less attention than those on carbohydrate and lipid metabolism, recent studies have increased our understanding of the mechanisms involved in the control of protein synthesis.The activities of several translation factors have been found to be controlled by insulin, explaining at least in part the stimulatory effect of insulin on translation. A newly discovered signaling system based on the Ser/Thr protein kinase, mTOR, has been found to have a key role in the control of mRNA translation. Protein synthesis and the control of carbohydrate metabolism have now been linked in unexpected ways, and many of the same signaling elements utilized by insulin to control glucose metabolism have been found to be involved in the control of protein synthesis. With these discoveries has come an appreciation that signaling molecules identified in studies of protein synthesis may turn out to be important in the control of carbohydrate and lipid metabolism. This chapter describes mechanisms underlying the rapid activation of mRNA translation by insulin. A brief overview of translation is provided as a framework for discussing insulin action (see Figs. 1 and 2 for schematic representations).

Joseph F. Christian

John C. Lawrence, Jr.
Department of Pharmacology, University of Virginia Health System

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Chapter category: Endocrine

Control of Protein Synthesis by Insulin

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