PHYSICAL ACTIVITY, PANCREATIC FUNCTION, AND OBESITY

  • Stern, Judith S, (PI)

Project: Research project

Description

While it is unlikely that obesity in humans is a single disease, most
obesities in experimental animals and man are accompanied by
hyperinsulinemia, inactivity, and altered diurnal rhythms of
glucocorticoids. For these studies, we will use four animal
models: 1) genetically obese Zucker rats (fafa), 2) genetically
obese and diabetic Wistar Kyoto "fatty" rats (WKY-fafa), 3)
genetically lean rats that become obese when fed a high fat/high
sucrose diet, and 4) exercised rats that rapidly regain weight when
they become inactive. Experiments are designed to: 1. Study mechanism(s) underlying hyperinsulinemia and its role in
development and maintenance of obesity. Evidence is
accumulating that the autonomic nervous system plays a key role
in establishment and maintenance of hyperinsulinemia. However,
studies of pancreatic insulin secretion are somewhat limited
because isolated islets or isolated pancreata are dennervated.
Using an in situ central nervous system (CNS)-intact pancreatic
perfusion system, for the the first time, we will be able to
directly study the contribution of the autonomic nervous system
to increased insulin secretion in obesity. Our hypothesis is that
autonomic control of the pancreas directly contributes to
increased insulin secretion in many forms of obesity. We propose
that the vagus nerve "over" stimulates insulin secretion via
efferent (to the pancreas) neurons which are "hyperactive" and
offset the afferent (to the brain) neurons which are inhibitory to
the pancreas via CNS reflexes. We also propose that "obesity-
resistant" and "obesity-susceptible" rats will be distinguished, in
part, by shifts in the balance between autonomic control of insulin
secretion 2. We will study the interaction of insulin and corticosterone
replacement in diabetic and adrenalectomized (ADX) obese and
lean Zucker rats on food intake, adiposity, and protein turnover.
We hypothesize that insulin will be less effective in the obese in
sparing negative effects of corticosterone on protein turnover. 3. We propose that key to weight regain after exercise in changes
in sympathetic tone to the pancreas and altered thermogenesis.
High fat diets increase this regain. 4. We will study the underlying mechanism by which obese rats
modify their fat intake. We propose that decreased fat intake in
the ADX obese rat is a function of a series of events which
decreases the "hedonic" response of an animal to fat and is
mediated through the opioid system.
StatusFinished
Effective start/end date4/1/773/31/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Obesity
Exercise
Insulin
Pancreas
High Fat Diet
Zucker Rats
Fats
Hyperinsulinism
Central Nervous System
Adiposity
Maintenance
Neurons
Weights and Measures
Pleasure
Vagus Nerve
Inbred WKY Rats
Thermogenesis
Autonomic Nervous System
Eating
Corticosterone

ASJC

  • Medicine(all)