Obesity and diabetic conditions are complex multifactorial disorders that affect approximately 50% of the U.S. adult population. Obesity is a known risk factor for diabetes mellitus, heart disease, hypertension, and even some forms of cancer. Overnutrition precipitates hyperinsulinemia, which promotes the storage of fat. The principal hormonal mediator of enteric insulin release in response to oral glucose is glucose-dependent insulinotropic polypeptide (GIP). We hypothesize that in addition to stimulating insulin release; GIP may function physiologically to directly enhance lipid deposition. Our hypothesis is further supported by Miyawaki et al, who recently demonstrated that mice deficient in the GIP receptor (GIPR) were protected from gaining weight when fed a high-fat diet compared to wild-type littermates. This observation suggests that inhibition of GIP signaling may prevent obesity. This grant proposal will 1) determine the role of GIP in the process of fat cell differentiation, and 2) identify downstream effectors of GIP signaling in adipocytes. By critically understanding GIP/GIPR signaling, our long-term objective is to antagonize GIP/GIPR and thereby prevent obesity and diabetes mellitus.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK067812-01A1
Application #
6883785
Study Section
Special Emphasis Panel (ZRG1-F06 (20))
Program Officer
Podskalny, Judith M,
Project Start
2005-02-15
Project End
2008-02-14
Budget Start
2005-02-15
Budget End
2006-02-14
Support Year
1
Fiscal Year
2005
Total Cost
$50,548
Indirect Cost
Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118
Song, Diane H; Wolfe, M Michael (2007) Glucose-dependent insulinotropic polypeptide and its role in obesity. Curr Opin Endocrinol Diabetes Obes 14:46-51
Chang, Albert J; Song, Diane H; Wolfe, M Michael (2006) Attenuation of peroxisome proliferator-activated receptor gamma (PPARgamma) mediates gastrin-stimulated colorectal cancer cell proliferation. J Biol Chem 281:14700-10