The overall aim of this application is to determine the mechanism(s) by which common bariatric surgical procedures alter carbohydrate metabolism. Very often, resolution of diabetes occurs in the early post-operative period prior to the development of significant weight loss. It has been suggested that bariatric surgery alters insulin action but few studies have examined insulin secretion or postprandial glucose fluxes in such patients. Recently, it has been shown that bypass of relatively short segments of the intestine are associated with remission of type 2 diabetes reinforcing the suggestion that hormonal signals from the excluded proximal gut favorably alter glucose metabolism. Another possibility is that enhanced distal intestinal delivery of nutrients stimulates hypersecretion of known or unknown hormones produced by the enteroendocrine system which ameliorate diabetes. Postprandial glucose tolerance is the net result of insulin secretion and action, intestinal uptake and splanchnic extraction, peripheral glucose uptake and suppression of endogenous glucose production. At the present time, little is known about how the various bariatric surgical procedures alter glucose homeostasis. It is essential that the effect of bariatric surgery and meal size on these parameters be understood and accurately measured. Enteroendocrine secretion is affected by the rate of intestinal delivery of calories and may also be modulated by the enteric nervous system and the rate of direct delivery of nutrients to enteroendocrine cells. Direct measurement of intestinal transit is also an important part of understanding how bariatric surgery alters intestinal secretion of hormones that may alter glucose metabolism.
The ability to understand how surgical procedures designed to produce weight loss ameliorate the metabolic disturbances seen in type 2 diabetes will allow a greater understanding of how intestinal hormones, together with caloric restriction, alter glucose metabolism. This may lead to new, targeted treatment strategies. It has been shown that common bariatric procedures cure type 2 diabetes independent of weight loss. Understanding the effect of these interventions on glucose metabolism and GLP-1 secretion (amongst other gut hormones) will immeasurably increase our ability to develop new treatment strategies in individuals affected with diabetes.
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