amorphastilbol and Diabetes-Mellitus--Type-2

In the present study, the anti-diabetic effects of amorphastilbol (APH) from Amorpha fruticosa (AF) were evaluated in high-fat-diet (HFD) mice. HFD-induced blood glucose and insulin levels are significantly reduced in AF extract or APH treatment groups. HFD-induced weight gain was reduced by AF treatment, which is accompanied by reduction of fat mass and adipocyte size and number in white adipose tissues. Furthermore, total cholesterol and low-density lipoprotein-cholesterol levels are decreased in AF- or APH-treated mice. In addition, AF and APH are able to improve insulin sensitivity through inhibition of protein tyrosine phosphatase 1B, a negative regulator of the insulin-signaling pathway. Taken together, the data suggest that AF has beneficial effects on glucose and lipid metabolism and its pharmacological effects are driven, in part, by its active component, APH. Therefore, AF and APH can be used as potential therapeutic agents against type 2 diabetes and associated metabolic disorders, including obesity, by enhancing glucose and lipid metabolism.

Topics: Animals; Anti-Obesity Agents; Cannabinoids; Cell Line; Diabetes Mellitus, Type 2; Diet, High-Fat; Glucose; Hypoglycemic Agents; Insulin Resistance; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Obesity; Protein Tyrosine Phosphatase, Non-Receptor Type 1

Peroxisome proliferator-activated receptors (PPARs) have been considered as desirable targets for metabolic syndrome treatments, even though their specific agonists have several side effects, including body weight gain, edema, and tissue failure. The effects of amorphastilbol (APH) on glucose- and lipid metabolism were investigated with in vitro 3T3-L1 adipocyte systems and in vivo db/db mice model. APH selectively stimulates the transcriptional activities of both PPARα and PPARγ, which are able to enhance fatty acid oxidation and glucose utilization. Furthermore, APH improves glucose and lipid impairment in db/db mice. More importantly, there are no significant side effects, such as weight gain or hepatomegaly, in APH-treated animals, implying that APH do not adversely affect liver or lipid metabolism. All our data suggest that APH can be used as potential therapeutic agents against type 2 diabetes and related metabolic disorders, including obesity, by enhancing glucose and lipid metabolism.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipose Tissue, White; Animals; Blood Glucose; Cannabinoids; Diabetes Mellitus, Type 2; Fatty Acids; Gene Expression Regulation; Hypoglycemic Agents; Liver; Male; Mice; Mice, Inbred C57BL; Oxidation-Reduction; PPAR alpha; PPAR gamma