Altered glucose homeostasis by sleep impairment

University Of Louisville, Louisville KY

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Abstract

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSAs), a condition characterized by repeated episodes of upper airway obstruction during sleep, affects 2-5 % of the general population. Extensive clinical data has clearly established an association between (OSAS), obesity and impaired glucose tolerance. If this association between OSAS and impaired glucose tolerance is causal than sleep apnea may be one of the more important risk factors for development of Type II diabetes. We will use two primary characteristics of sleep apnea, intermittent hypoxia and sleep fragmentation, in mouse models of OSAS to determine if components of sleep apnea are capable of causing disruption of glucose homeostasis. Most studies of sleep disorders and glucose regulation have focused on the development of insulin resistance. However, Type II diabetes cannot develop unless there is also at least partial failure of insulin secretion by pancreatic beta cells. Sleep apnea and intermittent hypoxia produce oxidative stress and beta cells are exquisitely sensitive to oxidative stress. To determine whether sleep apnea stresses or damages the beta cell we will measure insulin synthesis and secretion and test if beta cells exhibit signs of stress, particularly oxidative stress. To establish whether oxidative stress plays a critical role in apnea induced damage to glucose regulation we will test whether overexpression of antioxidant transgenes provide protection from intermittent hypoxia or sleep fragmentation. Our preliminary results indicate that obese mice are much more sensitive to the detrimental effects of sleep disruption on glucose tolerance and insulin secretion than are lean mice. Since obesity and sleep apnea are common and associated, many patients exhibit both pathologies. This may produce synergistic damage to glucose homeostasis. We will test the effect of OSAS on congenic strains of obese and lean mice.