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World Congress on the Insulin Resistance Syndrome, 2009
Cellular mechanisms of insulin resistance

1. Zachary T. Bloomgarden, MD

+ Author Affiliations

Zachary T. Bloomgarden, MD, is a practicing endocrinologist in New York, New York, and is affiliated with the Division of Endocrinology, Mount Sinai School of Medicine, New York, New York.

This is the first of four articles summarizing presentations at the Seventh World Congress on the Insulin Resistance Syndrome, held in San Francisco, California, on 5–7 November 2009, pertaining to cellular mechanisms of insulin resistance.
Circadian rhythms and insulin resistance

Peter Grant (Leeds, U.K.) introduced the topic of circadian rhythms and their relationship to insulin resistance. The thrifty genotype hypothesis (1) suggests a survival advantage of insulin resistance, presumably during periods of famine. Insulin resistance should then be considered a physiologic process, with duration the critical issue, so that prolonged insulin resistance leads to disease—rather than what might be considered beneficial insulin resistance after increased nutrient ingestion in preparation for famine. Animals that prepare themselves for hypernation have adipocyte hypertrophy, hyperphagia, inflammatory changes, hyperinsulinemai, hyperglycemia, and reduced energy expenditure—all short- to medium-term processes. Seasonal animals have marked insulin resistance just prior to hibernation (2), with seasonal cycling related to the fat phenotype; a secondary period of fat accumulation occurs during springtime. There is an endogenous clock that sets up oscillating systems in virtually every tissue, synchronized by a central clock regulatory mechanism. “You disrupt the clock at your own peril,” Grant noted, with sleep duration a risk factor for development of diabetes. Cardiovascular physiology is under circadian variation, affecting blood pressure, endothelial function, vascular tone, lipid metabolism, platelet and leukocyte function, and thrombosis. Effects of shift working in man include gastrointestinal, reproductive, and metabolic disturbances; insulin resistance; fasting and postprandial hypertriglyceridema; and increased risk of cardiovascular disease (CVD), “so this is not a minor change.” One could hypothesize that seasonal insulin resistance benefits the hibernating animal, but “man seems,” Grant said, “to have completely lost contact with ‘the animal,’ … [putting] on weight year after year.”

Joseph Bass (Chicago, IL) reviewed information about the molecular clock and its linkage to metabolic control. There are hypothalamic …
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