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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #319806
Title: Metabolic, anabolic, and mitogenic insulin responses: A tissue-specific perspective for insulin receptor activators

Author
item BEDINGER, DANIEL - University Of California
item Ferruzzi, Mario

Submitted to: Molecular and Cellular Endocrinology
Publication Type: Review Article
Publication Acceptance Date: 8/9/2015
Publication Date: 11/5/2015
Citation: Bedinger, D.H., Adams, S.H. 2015. Metabolic, anabolic, and mitogenic insulin responses: A tissue-specific perspective for insulin receptor activators. Molecular and Cellular Endocrinology. 415:143-156. doi: 10.1016/j.mce.2015.08.013.

Interpretive Summary: Insulin acts as the major regulator of the fasting-to-fed metabolic transition by altering substrate metabolism, promoting energy storage, and helping activate protein synthesis. In addition to its glucoregulatory and other metabolic properties, insulin can also act as a growth factor. The metabolic and mitogenic responses to insulin are regulated by divergent post-receptor signaling mechanisms downstream from the activated insulin receptor (IR). However, the anabolic and growthpromoting properties of insulin require tissue-specific inter-relationships between the two pathways, and the nature and scope of insulin-regulated processes vary greatly across tissues. Understanding the nuances of this interplay between metabolic and growth-regulating properties of insulin would have important implications for development of novel insulin and insulin-receptor (IR) modulator therapies that stimulate insulin receptor activation in both pathway- and tissue-specific manners. This review will provide a unique perspective focusing on the roles of "metabolic" and "mitogenic" actions of insulin signaling in various tissues, and how these networks should be considered when evaluating selective pharmacologic approaches to prevent or treat metabolic disease.

Technical Abstract: Insulin acts as the major regulator of the fasting-to-fed metabolic transition by altering substrate metabolism, promoting energy storage, and helping activate protein synthesis. In addition to its glucoregulatory and other metabolic properties, insulin can also act as a growth factor. The metabolic and mitogenic responses to insulin are regulated by divergent post-receptor signaling mechanisms downstream from the activated insulin receptor (IR). However, the anabolic and growthpromoting properties of insulin require tissue-specific inter-relationships between the two pathways, and the nature and scope of insulin-regulated processes vary greatly across tissues. Understanding the nuances of this interplay between metabolic and growth-regulating properties of insulin would have important implications for development of novel insulin and insulin-receptor (IR) modulator therapies that stimulate insulin receptor activation in both pathway- and tissue-specific manners. This review will provide a unique perspective focusing on the roles of "metabolic" and "mitogenic" actions of insulin signaling in various tissues, and how these networks should be considered when evaluating selective pharmacologic approaches to prevent or treat metabolic disease.