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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK082396-05
Application #
8640928
Study Section
Clinical and Integrative Diabetes and Obesity Study Section (CIDO)
Program Officer
Teff, Karen L
Project Start
2010-04-03
Project End
2015-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
5
Fiscal Year
2014
Total Cost
$298,907
Indirect Cost
$91,254
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Vella, Adrian (2014) ?-cell function after weight-loss induced by bariatric surgery. Physiology (Bethesda) 29:84-5
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Shah, Meera; Vella, Adrian (2014) Effects of GLP-1 on appetite and weight. Rev Endocr Metab Disord 15:181-7
Sathananthan, Matheni; Farrugia, Luca P; Miles, John M et al. (2013) Direct effects of exendin-(9,39) and GLP-1-(9,36)amide on insulin action, *-cell function, and glucose metabolism in nondiabetic subjects. Diabetes 62:2752-6
Vella, A (2013) Enteroendocrine secretion after Roux-en-Y gastric bypass: is it important? Neurogastroenterol Motil 25:1-3
Smushkin, Galina; Sathananthan, Matheni; Piccinini, Francesca et al. (2013) The effect of a bile acid sequestrant on glucose metabolism in subjects with type 2 diabetes. Diabetes 62:1094-101
Vella, Adrian (2013) Does caloric restriction alone explain the effects of Roux-en-Y gastric bypass on glucose metabolism? Not by a long limb. Diabetes 62:3017-8
Vella, Adrian; Zinsmeister, Alan R (2012) Predicting diabetes using measures of ?-cell function. Diabetes 61:562-3
Smushkin, Galina; Sathananthan, Airani; Man, Chiara Dalla et al. (2012) Defects in GLP-1 response to an oral challenge do not play a significant role in the pathogenesis of prediabetes. J Clin Endocrinol Metab 97:589-98
Kumar, Rajiv; Vella, Adrian (2011) Carbohydrate metabolism and the skeleton: picking a bone with the beta-cell. J Clin Endocrinol Metab 96:1269-71

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