Exp Mol Med.
2014 Jun;46(6):e102. 10.1038/emm.2014.40.
Inhibitory G proteins and their receptors: emerging therapeutic targets for obesity and diabetes
- Affiliations
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- 1Department of Medicine-Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin-Madison, Madison, WI, USA. mkimple@medicine.wisc.edu
- 2Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA.
- 3Duke University Medical Center Department of Pharmacology and Cancer Biology, Durham, NC, USA.
- KMID: 2155367
- DOI: http://doi.org/10.1038/emm.2014.40
Abstract
- The worldwide prevalence of obesity is steadily increasing, nearly doubling between 1980 and 2008. Obesity is often associated with insulin resistance, a major risk factor for type 2 diabetes mellitus (T2DM): a costly chronic disease and serious public health problem. The underlying cause of T2DM is a failure of the beta cells of the pancreas to continue to produce enough insulin to counteract insulin resistance. Most current T2DM therapeutics do not prevent continued loss of insulin secretion capacity, and those that do have the potential to preserve beta cell mass and function are not effective in all patients. Therefore, developing new methods for preventing and treating obesity and T2DM is very timely and of great significance. There is now considerable literature demonstrating a link between inhibitory guanine nucleotide-binding protein (G protein) and G protein-coupled receptor (GPCR) signaling in insulin-responsive tissues and the pathogenesis of obesity and T2DM. These studies are suggesting new and emerging therapeutic targets for these conditions. In this review, we will discuss inhibitory G proteins and GPCRs that have primary actions in the beta cell and other peripheral sites as therapeutic targets for obesity and T2DM, improving satiety, insulin resistance and/or beta cell biology.
Keyword
MeSH Terms
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Animals
Diabetes Mellitus, Type 2/drug therapy/*metabolism
GTP-Binding Protein alpha Subunits/genetics/*metabolism
Humans
Insulin-Secreting Cells/metabolism
Obesity/drug therapy/*metabolism
Receptor, Melatonin, MT2/genetics/*metabolism
Receptors, Adrenergic, alpha-1/genetics/*metabolism
Receptors, Prostaglandin/genetics/*metabolism
GTP-Binding Protein alpha Subunits
Receptor, Melatonin, MT2
Receptors, Adrenergic, alpha-1
Receptors, Prostaglandin
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