Selective Elevation of Adiponectin Production by the Natural Compounds Derived from a Medicinal Herb Alleviates Insulin Resistance and Glucose Intolerance in Obese Mice

Abstract

Adiponectin is an adipocyte-derived insulin-sensitizing hormone with antidiabetic, antiinflammatory, and antiatherosclerotic properties. A decreased serum level of adiponectin in obesity has been identified as an independent risk factor for diabetes and cardiovascular complications, suggesting that pharmacological intervention aimed at elevating adiponectin production might hold promise for the treatment and/or prevention of these diseases. Here we report the identification of two structurally related natural compounds (astragaloside II and isoastragaloside I) from the medicinal herb Radix Astragali that possess such an activity. Astragaloside II and isoastragaloside I selectively increased adiponectin secretion in primary adipocytes without any obvious effects on a panel of other adipokines. Furthermore, an additive effect on induction of adiponectin production was observed between these two compounds and rosiglitazone, a thiazolidinedione class of insulin-sensitizing drugs. Chronic administration of astragaloside II and isoastragaloside I in both dietary and genetic obese mice significantly elevated serum levels of total adiponectin and selectively increased the composition of its high molecular weight oligomeric complex. These changes were associated with an alleviation of hyperglycemia, glucose intolerance, and insulin resistance. By contrast, the beneficial effects of these two compounds on insulin sensitivity and glucose metabolism were diminished in adiponectin knockout mice. In conclusion, our results suggest that pharmacological elevation of circulating adiponectin alone is sufficient to ameliorate insulin resistance and diabetes and support the use of adiponectin as a biomarker for future drug discovery. The two natural compounds might provide the lead as a novel class of therapeutics for obesity-related diseases.

Systematic review of the renal protective effect of Astragalus membranaceus (root) on diabetic nephropathy in animal models

“…Studies which focused on both dietary and genetically obese mice treated with AM (root) derivatives have shown significant increases in circulating adiponectin in association with potent reduction in insulin resistance and glucose intolerance, suggesting that AM (root) may be a therapeutic candidate for the treatment of obesity-related disease (Xu et al, 2009). AM (root) was able to reverse hyperglycemia and protect pancreatic islets in type 1 DM in NOD mice by changing the predominant form of lymphocytes/cytokines from Th1 to Th2, thus preventing lymphocyte infiltration of the pancreas (Chen et al, 2008a,b).…”

Major Urinary Protein-1 Increases Energy Expenditure and Improves Glucose Intolerance through Enhancing Mitochondrial Function in Skeletal Muscle of Diabetic Mice

“…To establish a dietary obese mouse model, 4-week-old male C57BL/6J mice were fed a 19.33 kJ/g high fat diet (D12451, Research Diet, New Brunswick, NJ) containing 45 Kcal % fat, 20 Kcal % protein, and 35 Kcal % carbohydrate for 10 weeks as described previously (24). For the intraperitoneal glucose tolerance test, mice that were fasted overnight (16 h) were given a glucose load by intraperitoneal injection (1 g of glucose/kg of body weight).…”

Paradox of using intensive lowering of blood glucose in diabetics and strategies to overcome it and decrease cardiovascular risks

“…A decreased adiponectin serum level in obese patients has been identified as an independent risk factor for diabetes and cardiovascular complications. (41) Research by Xu, et al (42) suggested that astragaloside Ⅱ and isoastragaloside Ⅰ from the medicinal herb Radix Astragali increased adiponectin secretion. Adenosine monophosphate-activated protein kinase (AMPK) had cardioprotective effects against ischemic injury and the forkhead transcription factor 3 (FOXO3) had been identified as a downstream marker of AMPK.…”