2-(n-(7-nitrobenz-2-oxa-1-3-diazol-4-yl)amino)-2-deoxyglucose and baicalin

Although baicalin could attenuate obesity-induced insulin resistance, the detailed mechanism of baicalin on glucose uptake has not been sufficiently explored as yet. The aim of this study was to survey if baicalin might facilitate glucose uptake and to explore its signal mechanisms in L6 myotubes.. L6 myotubes were treated with 100, 200, 400 μM baicalin for 6 h, 12 h and 24 h in this study. Then 2-NBDG and insulin signal protein levels in myotubes of L6 cells were examined.. We discovered that administration of baicalin enhanced GLUT4, PGC-1α, pP38MAPK, pAKT and pAS160 contents, as well as GLUT4 mRNA and PGC-1α mRNA levels in L6 myotubes. The beneficial metabolic changes elicited by baicalin were abrogated in myotubes of L6 by P38MAPK or AKT inhibitors.. These results suggest that baicalin promoted glucose uptake in myotubes by differential regulation on P38MAPK and AKT activity. In conclusion, these data provide insight that baicalin is a powerful and promising agent for the treament of hyperglycemia via AKT/AS160/GLUT4 and P38MAPK/PGC1α/GLUT4 pathway.

Topics: 4-Chloro-7-nitrobenzofurazan; Animals; Cells, Cultured; Deoxyglucose; Flavonoids; Glucose; Glucose Transporter Type 4; Hypoglycemic Agents; Insulin; Muscle Fibers, Skeletal; Muscle, Skeletal; Oncogene Protein v-akt; p38 Mitogen-Activated Protein Kinases; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Rats; Signal Transduction; Subcellular Fractions

Obesity may cause several metabolic complications, including insulin resistance and type 2 diabetes mellitus. Despite great advances in medicine, people still keep exploring novel and effective drugs for treatment of obesity and insulin resistance. The aim of this study was to survey if baicalin might ameliorate obesity-induced insulin resistance and to explore its signal mechanisms in skeletal muscles of mice. Diet-induced obese (DIO) mice were given 50 mg/kg baicalin intraperitoneally (i.p.) once a day for 21 days, and C2C12 myotubes were treated with 100, 200, 400 μM baicalin for 12 h in this study. Then insulin resistance indexes and insulin signal protein levels in skeletal muscles were examined. We discovered that administration of baicalin decreased food intake, body weight, HOMA-IR and NT-PGC-1α levels, but enhanced GLUT4, PGC-1α, pP38MAPK, pAKT and pAS160 contents, as well as GLUT4 mRNA, PGC-1α mRNA, PPARγ mRNA, GLUT1 mRNA expression in skeletal muscles of obese mice and myotubes of C2C12 cells, and reversed high fat diet-induced glucose and insulin intolerance, hyperglycemia and insulin resistance in the mice. These results suggest that baicalin is a powerful and promising agent for treatment of obesity and insulin resistance via Akt/AS160/GLUT4 and P38MAPK/PGC1α/GLUT4 pathway.

Topics: 4-Chloro-7-nitrobenzofurazan; Animals; Blood Glucose; Body Weight; Cell Line; Cell Membrane; Deoxyglucose; Feeding Behavior; Flavonoids; Glucose Tolerance Test; Glucose Transporter Type 1; Glucose Transporter Type 4; GTPase-Activating Proteins; Homeostasis; Injections, Intraperitoneal; Insulin Resistance; Male; Mice, Inbred C57BL; Muscle, Skeletal; Obesity; Phosphorylation; PPAR gamma; Proto-Oncogene Proteins c-akt; RNA, Messenger; Signal Transduction