Department of Biomedical Sciences
Email: email@example.com; Phone: 607-253-3552
Sponsor: University of California Davis-(NIH/NIDDK)
Grant Number: 201121154-01
Title: Dissecting Mechanism by which GI Surgery Delays Diabetes Onset in UCD-T2GM Rats
Project Amount: $86,296
Project Period: 09/01/13-04/30/14
DESCRIPTION (Provided by Applicant): The goal of this project is to investigate the relative contribution of increases GLP-1, increased bile acids and ghrelin suppression to the effects of VSG to improve glucose homeostasis and delay the onset of diabets in UCD-T2DM rats. Three separate studies involving addition and abiation of the changes will be performed. Study 1a will include: sham, sham + sitagliptin, VSG, VSG + Exendin 9-39. Study 1b will include: sham, sham + cholic acid, VSG, VSG + ABST inhibitor. Study 1c will include: sham, sham + antagonist, VSG, VSG + ghrelin replacement. All groups will be weight matched. In all studies in vivo glucose homestasis, B-cell mass, ectopic lipid deposition, ER stress and plasma, liver and intestinal content bile acid profiles will be assessed.
Dr. Cummings' laboratory will also investigate the relative contribution of GLP-1 and bile acids to the effect of IT surgery to improve glucose homeostasis and delay the onset of diabetes in UCD-T2DM rats. Two separate studies will be preformed as outlined for Study 1a and Study 1b in SA1.
In addition, the Cummings' laboratory will also test the hypothesis that VSG and IT surgery in combination will prevent the onset of diabetes in UCD-T2DM rats. To achieve this aim there will be 6 weight-matched groups- sham-IT, sham-VSG, sham-IT/VSG, IT, VSG, IT/VSG, which be followed until diabetes onset or up to a 2 years of age. In vivo glucose homeostatsis will be assessed and tissues take from a subset of animals at 1.5 months after surgery for assessment of B-cells mass, ER stress and bile acid profiles of plasma, liver and intestinal contents. New therapeutic targets will be pursued by performing micoarry analysis of enteroendocrine cells isolated from selected gut segments and analyzing gut microbial populations by pyrosequencing.