INTESTINAL BYPASS SURGERY IN HIBERNATION

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Knowledge of the mechanisms by which the mammalian intestine adaptively regulates its structure and function is essential to the treatment and prevention of numerous gastrointestinal pathologies; yet these mechanisms are not entirely clear. Our aim is to identify mechanisms involved in the maintenance of mucosal function of normal and bypassed jejunum in hibernating and active 13-lined ground squirrels. Ground squirrels do not eat or drink during the hibernation period, yet transport function appears to be preserved until emergence in the spring. This is in contrast to diversion of nutrients from the non-hibernating mammalian intestine, either by fasting or intestinal bypass surgery, which results in significant reductions in mucosal mass and absorptive capacity. Hibernating squirrels with intact intestines, hibernators that have undergone intestinal bypass surgery, winter-active, fed ground squirrels with normal intestines and winter active, bypassed squirrels will be used to test the hypothesis that bypassed intestine in the hibernator is prevented from the atrophic changes that occur in non-hibernators. Small intestinal transport function will be assessed by measuring transepithelial fluxes of glucose and sodium in jejunal segments set up in modified Ussing-type chambers that are equipped to simultaneously record electrical properties of the tissue. The unidirectional influx of glucose across the brush border membrane will be measured to determine if changes in the number of glucose carrier sites or the affinity of glucose for its carrier are responsible for adaptive changes in transport function. The mass of absorptive cells in each experimental group will be estimated by measuring the wet and dry weights, protein and DNA content of mucosa harvested from segments adjacent to those used in the physiological experiments. Blood and tissue samples will be collected from squirrels used in the transport experiments for later analysis of peptides and other messengers that might be involved in the maintenance of intestinal structure and function. These studies are expected to enhance understanding of mechanisms that contribute to adaptive maintenance of intestinal function during hibernation.