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 #
5R01DK082396-03
Application #
8244530
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
2012-04-01
Budget End
2013-03-31
Support Year
3
Fiscal Year
2012
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
Rizza, Robert A; Toffolo, Gianna; Cobelli, Claudio (2016) Accurate Measurement of Postprandial Glucose Turnover: Why Is It Difficult and How Can It Be Done (Relatively) Simply? Diabetes 65:1133-45
Varghese, Ron T; Viegas, Ivan; Barosa, Cristina et al. (2016) Diabetes-Associated Variation in TCF7L2 Is Not Associated With Hepatic or Extrahepatic Insulin Resistance. Diabetes 65:887-92
Shah, Meera; Varghese, Ron T; Miles, John M et al. (2016) TCF7L2 Genotype and α-Cell Function in Humans Without Diabetes. Diabetes 65:371-80
Dalla Man, Chiara; Micheletto, Francesco; Sathananthan, Matheni et al. (2016) Model-Based Quantification of Glucagon-Like Peptide-1-Induced Potentiation of Insulin Secretion in Response to a Mixed Meal Challenge. Diabetes Technol Ther 18:39-46
Vella, Adrian; Cobelli, Claudio (2015) Defective Glucagon-Like Peptide 1 Secretion in Prediabetes and Type 2 Diabetes Is Influenced by Weight and Sex. Chicken, Egg, or None of the Above? Diabetes 64:2324-5
Matveyenko, Aleksey; Vella, Adrian (2015) Regenerative medicine in diabetes. Mayo Clin Proc 90:546-54
Javed, Asma; Balagopal, P Babu; Vella, Adrian et al. (2015) Association between thyrotropin levels and insulin sensitivity in euthyroid obese adolescents. Thyroid 25:478-84
Sathananthan, Matheni; Shah, Meera; Edens, Kim L et al. (2015) Six and 12 Weeks of Caloric Restriction Increases β Cell Function and Lowers Fasting and Postprandial Glucose Concentrations in People with Type 2 Diabetes. J Nutr 145:2046-51
Shah, Meera; Law, Jennie H; Micheletto, Francesco et al. (2014) Contribution of endogenous glucagon-like peptide 1 to glucose metabolism after Roux-en-Y gastric bypass. Diabetes 63:483-93
Sathananthan, Matheni; Ikramuddin, Sayeed; Swain, James M et al. (2014) The effect of vagal nerve blockade using electrical impulses on glucose metabolism in nondiabetic subjects. Diabetes Metab Syndr Obes 7:305-12

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