Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of the murine-selective beta3 adrenoceptor agonist CL-316,243 corrects obesity and elevated blood glucose in diabetic rodents. This antiobesity effect is attributed to an increase in the thermogenic activity of brown adipose tissue (BAT). The antidiabetic effect is unknown, but has been attributed to the decline in body weight and plasma free fatty acids (FFAs). This study using the euglycemic-hyperinsulinemic clamp method was performed in nonobese, nondiabetic Sprague-Dawley rats fed normal rodent chow to determine if the beta3 agonist could improve insulin sensitivity and/or responsiveness in the absence of weight loss or lowering of circulating FFAs. Subcutaneous miniosmotic pumps delivered either saline to control or 1 mg x kg(-1) x day(-1) of CL-316,243 for 10-12 days. Fed plasma glucose, insulin, and FFA levels were similar between the groups. Significant increases in food consumption, resting metabolic rates, and body core temperatures occurred, but only after 7 days of treatment. A 14% decrease in the respiratory quotient was also observed. Plasma glucose and insulin excursions in response to an oral glucose load (2 g/kg) on day 11 were unaltered. Cl-316,243 treatment resulted in a decrease in abdominal and epididymal white fat pad weights, while interscapular brown adipose tissue (IBAT) weight doubled. Basal and insulin-stimulated whole-body glucose disposal rates were increased, while hepatic glucose output was suppressed to a greater extent in the CL-316,243 animals after 10 days of uninterrupted treatment. Chronic treatment with CL-316,243 resulted in an increase in basal and insulin-stimulated [3H]2-deoxyglucose (2-DG) uptake by the retroperitoneal and epididymal white tissue and IBAT, but skeletal muscle 2-DG uptake under the same conditions was unaltered. These studies demonstrate that treatment with CL-316,243 improves basal and insulin-stimulated glucose disposal, and these effects occurred in the absence of a decrease in body weights and FFA concentrations. A particularly interesting observation was that the tissues responsible for this effect were white and brown adipose tissue, while skeletal muscle remained unaffected.
Diabetes 1997 Aug
PMID:CL-316,243, a beta3-specific adrenoceptor agonist, enhances insulin-stimulated glucose disposal in nonobese rats. 923 48

Diabetes mellitus is a chronic metabolic disorder, characterized by glucose overproduction and glucose underutilization. Current therapy for T2DM includes drugs, like metformin, glitazones, sulphonyl ureas, etc. Extensive research has been carried out world wide on molecular targets for T2DM like PPARgamma, PTP1B, DPP-IV, GSK-3, cannabinoid receptor, fructose-bisphosphatases, beta3 adrenoceptor, etc. in the development of newer anti-diabetic agents. These therapeutic targets are quite important and most of them are suitable for in silico analysis. Hence, many molecular modeling and informatics studies like, molecular docking, pharmacophore mapping, 3D-QSAR, virtual screening, quantum chemical studies, and pharmacoinformatics like bioinformatics and chemoinformatics studies have been performed on the drugs/leads/targets associated with T2DM. Several of these in silico efforts are exemplary studies; the methodologies adopted in these studies can be emulated in many other therapeutic areas. A review of the rational approaches reported in designing anti-diabetic agents is presented in this article.
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PMID:Modeling and informatics in designing anti-diabetic agents. 1822 Jul 88