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The Role of Insulin‐like Signaling for the Central and Peripheral Regulation of Nutrient Homeostasis and Life Span
Author(s) -
White Morris F.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.329.2
Subject(s) - insulin , insulin receptor , insulin resistance , biology , glucose homeostasis , hyperinsulinemia , homeostasis , endocrinology , irs2 , medicine , nutrient sensing , insulin oscillation , signal transduction , microbiology and biotechnology
It is incontrovertible that insulin‐like signaling is critical for development and growth of metazoans: Animals cannot survive without insulin‐like signaling, as it regulates nutrient storage and utilization throughout life. Regardless, the life‐span of lower metazoans‐C. elegans and Drosophila‐benefits from reduced insulin secretion or attenuation of the insulin‐like signaling cascades. One of the most important effects of insulin in higher animals and humans is to maintain blood glucose concentration within a narrow physiologic range. While glucose homeostasis is important, insulin‐like signaling can have detrimental effects upon life span. In higher animals and humans, reduced insulin secretion or resistance to the action of insulin causes glucose intolerance that can progress to life‐threatening diabetes. During insulin resistance, compensatory hyperinsulinemia is essential to prevent the fatal effects of hyperglycemia owing to insulin resistance. However, increased circulating insulin might have damaging effects upon peripheral tissues and the brain that can promote age‐related disease and reduce life span. By manipulating the expression of the insulin receptor substrates (Irs1, Irs2 and Irs4) in mice, we reveal the role of insulin‐like signaling upon peripheral and central nutrient homeostasis, and suggest that the brain is a site where reduced insulin‐like signaling can have a consistent effect to extend mammalian lifespan‐just as reduced insulin‐like signaling extends the life span of worms and flies.