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.
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

We analyzed association between viewing two-dimensional computed tomography (2D CT) images in addition to radiographs with radial head treatment recommendations after accounting for patient and surgeon factors in a survey-based experiment. Methods: One hundred and fifty-four surgeons reviewed 15 patient scenarios with terrible triad fracture dislocations of the elbow. Surgeons were randomized to view either radiographs only or radiographs and 2D CT images. The scenarios randomized patient age, hand dominance, and occupation. For each scenario, surgeons were asked if they would recommend fixation or arthroplasty of the radial head. Multi-level logistic regression analysis identified variables associated with radial head treatment recommendations. Results: Reviewing 2D CT images in addition to radiographs had no statistical association with treatment recommendations. A higher likelihood of recommending prosthetic arthroplasty was associated with older patient age, patient occupation not requiring manual labor, surgeon practice location in the United States, practicing for five years or less, and the subspecialties “trauma” and “shoulder and elbow.” Conclusions: The results of this study suggest that in terrible triad injuries, the imaging appearance of radial head fractures has no measurable influence on treatment recommendations. Personal surgeon factors and patient demographic characteristics may have a larger role in surgical decision making. Level of evidence: Level III, therapeutic case-control study