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

The liver is a vital organ in vertebrates and has a wide range of functions, including glucose absorption, glycogen storage and glucose production. Fibroblast growth factor (FGF)-21 is a metabolic regulator that is primarily produced by the liver. In this paper, we studied the effect of FGF-21 on glucose metabolism in the liver.. The glucose uptake of cells was detected by 2-Deoxy-d-[3H] glucose; the synergy between insulin and FGF-21 was evaluated. The mRNA expression of GLUT1-4, G6Pase and PEPCK was detected by real-time PCR. Glycogen synthesis was examined by the anthrone method. Blood samples to monitor glucose in db/db diabetic mice were obtained by tail snip. Glucose metabolism in the liver and adipose tissues was observed by fluorescence microscopy.. In this study, FGF-21 stimulated glucose uptake by liver cells in both a dose and time-dependent manner, and at the same time, FGF-21 specifically stimulated GLUT1 expression in the liver cells. Furthermore, FGF-21 demonstrated a synergistic effect with insulin on glucose absorption, which is in accordance with enhanced GLUT-1 and -4 expression. Treatment with FGF-21 increased glycogen storage in liver cells. Consistent with in vitro results, FGF-21 lowered the plasma glucose level and stimulated GLUT1 expression and glycogen synthesis in db/db diabetic mice. Simultaneously, FGF-21 inhibited the gene expression of G6Pase and PEPCK.. Our results suggest that FGF-21 clears up plasma glucose by stimulating glucose absorption in the liver of diabetic animals and decreases glucose release from the liver by inhibiting gluconeogenesis. Overall, these data indicate that the liver is an important target organ of FGF-21 to regulate glucose metabolism.

Topics: 4-Chloro-7-nitrobenzofurazan; Adipose Tissue; Animals; Cells, Cultured; Deoxyglucose; Fibroblast Growth Factors; Gluconeogenesis; Glucose; Glucose Transporter Type 1; Glucose Transporter Type 4; Glucose-6-Phosphatase; Glycogen; Hep G2 Cells; Hepatocytes; Humans; Insulin; Liver; Mice; Mice, Obese; Obesity; Phosphoenolpyruvate Carboxykinase (ATP); Recombinant Proteins

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