monascin and Insulin-Resistance

Several lines of evidence have implicated high levels of advanced glycation endproducts (AGEs) in diabetes. Pancreas impairment caused by AGEs has been found in recent studies. Monascin (MS) and monacolin K (MK) are active compounds identified from Monascus-fermented products, which have been reported to inhibit inflammation and improve insulin resistance. In order to confirm the protective effects of MS and MK on pancreatic function, BALB/c mice were treated with AGEs via intraperitoneal injection for 22 weeks to induce hyperglycemia, and the pancreas-protecting mechanism of MS and MK from AGE-induced damage was investigated. We found that the expression of pancreatic and duodenal homeobox-1 (PDX-1) and glucose transporter 2 (GLUT2) was recovered by MS or MK administration to AGE-treated mice. In addition, MS strongly improved performance in the oral glucose tolerance test (OGTT) and the insulin tolerance test (ITT), suggesting that MS sensitized to insulin in AGE-treated mice. Both MS and MK elevated pancreatic insulin expression when compared to the AGE-treated group, suggesting that MS and MK attenuated AGE-induced pancreatic dysfunction. Histopathology studies showed that intraperitoneal injection of AGEs did not result in pancreas damage. These findings confirm that the potential mechanism of AGEs on pancreatic dysfunction involves the induction of inflammation and the suppression of PDX-1 and GLUT2 expression. Taken together, MS and MK may be developed as an anti-diabetic agent in the future.

Topics: Animals; Diabetes Mellitus; Female; Fermentation; Glucose Tolerance Test; Glycation End Products, Advanced; Heterocyclic Compounds, 3-Ring; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Lovastatin; Male; Mice; Mice, Inbred BALB C; Monascus; Oryza; Pancreas

Chronic inflammation in muscle tissue causes insulin resistance and type-2 diabetes. Peroxisome proliferator-activated receptor (PPAR) ligands are reported to activate the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, including pioglitazone, which belong to the thiazolidinedione (TZD). Monascin (MS), a Monascus metabolite, has been reported to exert anti-inflammatory activity in our recent study. Therefore, the alleviating mechanism of MS on tumor necrosis factor-α (TNF-α; 20ng/mL) induced insulin resistance in C2C12 cells was investigated in this study. Results showed that MS increased the uptake of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) in C2C12 myotubes. This result was associated with both PPAR-γ activity and PI3K/Akt pathway caused by MS inhibited p-JNK activity and prevented PPAR-γ phosphorylation. Moreover, we found that MS may act a PPAR-γ agonist to improve insulin sensitivity, and this issue was further confirmed by PPAR-γ antagonist (GW9662). Briefly, MS as pioglitazone, stabilized PPAR-γ structure and diminished PPAR-γ phosphorylation thereby improving insulin resistance.

Topics: 4-Chloro-7-nitrobenzofurazan; Animals; Blotting, Western; Cell Line; Deoxyglucose; Heterocyclic Compounds, 3-Ring; Insulin Resistance; Mice; Monascus; Muscle Fibers, Skeletal; Phosphatidylinositol 3-Kinases; Phosphorylation; PPAR gamma; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha