GIP-Overexpressing Mice Demonstrate Reduced Diet-Induced Obesity and Steatosis, and Improved Glucose Homeostasis
Clee, Susanne M.
Isales, Carlos M.
McIntosh, Christopher H. S.
MetadataShow full item record
AbstractGlucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that potentiates glucose-stimulated insulin secretion during a meal. Since GIP has also been shown to exert b-cell prosurvival and adipocyte lipogenic effects in rodents, both GIP receptor agonists and antagonists have been considered as potential therapeutics in type 2 diabetes (T2DM). In the present study, we tested the hypothesis that chronically elevating GIP levels in a transgenic (Tg) mouse model would increase adipose tissue expansion and exert beneficial effects on glucose homeostasis. In contrast, although GIP Tg mice demonstrated enhanced b-cell function, resulting in improved glucose tolerance and insulin sensitivity, they exhibited reduced diet-induced obesity. Adipose tissue macrophage infiltration and hepatic steatosis were both greatly reduced, and a number of genes involved in lipid metabolism/inflammatory signaling pathways were found to be down-regulated. Reduced adiposity in GIP Tg mice was associated with decreased energy intake, involving overexpression of hypothalamic GIP. Together, these studies suggest that, in the context of over-nutrition, transgenic GIP overexpression has the potential to improve hepatic and adipocyte function as well as glucose homeostasis.
CitationPLoS One. 2012 Jul 3; 7(7):e40156
- GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet.
- Authors: McClean PL, Irwin N, Cassidy RS, Holst JJ, Gault VA, Flatt PR
- Issue date: 2007 Dec
- Chemical gastric inhibitory polypeptide receptor antagonism protects against obesity, insulin resistance, glucose intolerance and associated disturbances in mice fed high-fat and cafeteria diets.
- Authors: Gault VA, McClean PL, Cassidy RS, Irwin N, Flatt PR
- Issue date: 2007 Aug
- Chronic reduction of GIP secretion alleviates obesity and insulin resistance under high-fat diet conditions.
- Authors: Nasteska D, Harada N, Suzuki K, Yamane S, Hamasaki A, Joo E, Iwasaki K, Shibue K, Harada T, Inagaki N
- Issue date: 2014 Jul
- Attenuated secretion of glucose-dependent insulinotropic polypeptide (GIP) does not alleviate hyperphagic obesity and insulin resistance in <i>ob/ob</i> mice.
- Authors: Shimazu-Kuwahara S, Harada N, Yamane S, Joo E, Sankoda A, Kieffer TJ, Inagaki N
- Issue date: 2017 Mar
- Glucose-dependent Insulinotropic Polypeptide (GIP): From prohormone to actions in endocrine pancreas and adipose tissue.
- Authors: Ugleholdt R
- Issue date: 2011 Dec