ginsenoside-m1 and Insulin-Resistance

Topics: Diabetes Mellitus, Type 2; Dynamins; Fatty Acids; Humans; Insulin Resistance; Mitophagy; Muscle, Skeletal; Protein Kinases

Topics: Adipose Tissue; Animals; Diet, High-Fat; Ginsenosides; Inflammation; Insulin Resistance; Macrophages; Mice; Mice, Inbred C57BL; Obesity; Phosphatidylinositol 3-Kinases; PPAR gamma

Obesity is often accompanied by chronic low-grade inflammation, which aggravates the disorder of lipid metabolism and leads to insulin resistance (IR). Macrophage activation plays an important role in inflammation. Ginsenoside Compound K (CK) is an active metabolite of ginsenoside Rb1, which is adopting to an anti-inflammatory effective substance. In order to clarify the mechanism of ginsenoside CK on the regulation of macrophage activation in adipose tissue, the macrophage model was incubated with the supernatant of hypertrophic adipocytes, and the co-culture models of Raw264.7 and 3T3-L1 were established. The levels of related cytokines, macrophage polarization and protein expression in inflammatory signaling pathway were measured. The results showed that ginsenoside CK significantly inhibited the increase of MCP-1 and TNF-α induced by the supernatant of hypertrophic adipocytes, promoted the expression of IL-10, inhibited the activation of inflammatory macrophages and increased the expression of anti-inflammatory macrophages. Similarly, ginsenoside CK inhibited the migration of Raw264.7, blocked the activation of NF-κB, and up-regulated the expression of PPARγ. In addition, ginsenoside CK also promotes the expression of IRS-1 in insulin signal pathway. The experimental results proved that ginsenoside CK plays a crucial role in alleviating inflammation and insulin resistance in obesity, and inhibits macrophage activation through the key protein PPARγ.

Topics: 3T3-L1 Cells; Animals; Ginsenosides; Humans; Insulin Resistance; Macrophage Activation; Mice; Obesity; PPAR gamma; RAW 264.7 Cells

Compound K (CK) is a final metabolite of panaxadiol ginsenosides from Panax ginseng. Although anti-diabetic activity of CK has been reported in recent years, the molecular mechanism of CK in the treatment of diabetes mellitus remains unclear. In the present investigation, we established a rat model of type 2 diabetes mellitus (T2DM) with insulin resistance using high-fat diet (HFD) and streptozotocin (STZ), and attempted to verify more details and exact mechanisms in the treatment of T2DM. CK was administered orally at three doses [300, 100 and 30 mg/kg bodyweight (b.w.)] to the diabetic rats. Bodyweight, food-intake, fasting blood glucose (FBG), fasting serum insulin (FINS), insulin sensitivity (ISI), total glycerin (TG), total cholesterol (TC), as well as oral glucose tolerance test (OGTT) were evaluated in normal and diabetic rats. According to our results, CK could improve bodyweight and food-intake of diabetic rats. CK exhibited dose-dependent reduction of FBG, TG and TC of diabetic rats. CK treatment also enhanced FINS and ISI. Meanwhile, the glucose tolerance observed in the present study was improved significantly by CK. It is concluded from the results that CK may have improving effects on hyperglycemia and insulin resistance of diabetic rats. Furthermore, research showed that CK could promote the expression of InsR, IRS1, PI3Kp85, pAkt and Glut4 in skeletal muscle tissue of diabetic rats. These results indicate that the hypoglycemic activity of CK is mediated by improvement of insulin sensitivity, which is closely related to PI3K/Akt signaling pathway.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Ginsenosides; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Lipids; Male; Molecular Structure; Panax; Plant Roots; Rats; Rats, Wistar; Signal Transduction; Streptozocin

Compound K (CK) is a major intestinal metabolite of ginsenosides derived from ginseng radix. In our preliminary studies, CK has shown to exhibit anti-hyperglycemic effect through its insulin-secreting action, similar to that of insulin secretagogue sulfonylureas. Metformin, a biguanide, improves insulin resistance by reducing gluconeogenesis and enhancing peripheral glucose uptake, promoting reduction of the plasma glucose level. The aim of this study was to compare the anti-diabetic effects of CK and metformin due to differences in their mechanisms of action and also to investigate whether treatment of CK and metformin in combination show synergistic or additive effects compared to each drug alone. Seven week-old male db/db mice were treated for 8 weeks. CK was given at a dose of 10 mg/kg, metformin at 150 mg/kg and the same dosage of each drug was applied to CK plus metformin combination group. Significant improvements were observed in plasma glucose and insulin levels, homeostasis model assessment-insulin resistance (HOMA-IR) index and in hematoxylin and eosin-stained liver tissues in combination group. Although further studies to elucidate the benefits of co-administration of CK and metformin are needed, our findings may provide basis to the discovery of a new combination therapy on diabetes control in type 2 diabetics.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Ginsenosides; Glucose Tolerance Test; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Metformin; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Mutant Strains; Random Allocation; Time Factors