DYSREGULATION OF GLUCOSE HOMEOSTATIS IN AGING

Project: Research project

Project Details

Description

DESCRIPTION (Adapted from the Applicant's Abstract): Impaired glucose
metabolism and increased visceral/abdominal fat are common phenomena in
aging. Impaired glucose metabolism is characterized mainly by increased
glucose and insulin levels, and a higher prevalence of diabetes mellitus.
Such dysregulation may be associated with impairments in insulin action on
the muscle and liver, and a decreased ability to secrete insulin by the
beta-cells of the pancreas. An increase in visceral/abdominal fat, more so
than a general increase in fat mass, is a specific risk factor for a variety
of conditions such as hyperlipidemia and diabetes, resulting in increased
cardio-vascular mortality with aging. The investigators have previously
characterized aging animal models that exhibit some of the metabolic
features of human aging, and demonstrated the major role that age-related
changes in body composition have on the impairment in hepatic and peripheral
insulin action. Interestingly, longevity is increased in caloric restricted
animal models, supporting the notion that fat mass has deleterious effects
leading to mortality. They hypothesize that the typical increase in
visceral/abdominal fat determines the impairment in glucose metabolism seen
in aging. They will test this hypothesis by preventing the increase in
visceral/abdominal fat in rodents, and studying whether the age-related
impairments in peripheral and hepatic insulin action, and in insulin
secretion are thereby averted. Furthermore, they will determine the
molecular physiology by which visceral/abdominal fat exerts its effects on
glucose metabolism in aging. In these studies animals will be either ad
libidum fed or subjected to chronic interventions by caloric restriction and
by beta3-adrenoreceptor agonists, resulting in a spectrum of
visceral/abdominal fat weights. The effect of the changes induced in body
composition on peripheral and hepatic glucose metabolism, and insulin
secretion will be determined in vivo. Muscle, liver and pancreatic tissue
will be analyzed to determine the relevant substrates, enzyme activities,
and gene expressions after acute manipulations in aging rats.
StatusFinished
Effective start/end date9/30/978/31/98

Funding

  • National Institute on Aging

ASJC

  • Geriatrics and Gerontology
  • Endocrine and Autonomic Systems
  • Endocrinology
  • Nutrition and Dietetics
  • Endocrinology, Diabetes and Metabolism

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