ABSTRACT
Aim To investigate the role of GDF11 in palmitate induced skeletal muscle insulin resistance.Methods The C2C12 cells were sorted into control group, GDF11 intervention group, palmitate group and GDF11 combined with palmitate group.Cell viability was measured by CCK-8, and the glucose uptake was determined by 2NBDG.The mRNA level of myotube marker genes(desmin,myogenin), insulin mediate glucose uptake related genes(GLUT-4,IRS-1) and PGC-1α were tested by RT-PCR.The protein expression of PGC-1α was detected by western blot.Results GDF11 had little effect on cell viability of skeletal muscle cells.Compared with control group, the glucose uptake and the expression of GLUT-4,IRS-1,PGC-1α were significantly decreased by palmitate intervention.Compared with palmitate group, the glucose uptake and the expression of GLUT-4,IRS-1,PGC-1α were not significantly changed by GDF11.Conclusion Palmitate can induce skeletal muscle cell insulin resistance, but GDF11 may not significantly improve the skeletal muscle cell insulin resistance.
ABSTRACT
Objective To investigate the effects of growth differentiation factor 11 ( GDF11 ) on β-cell function in db/db mice and its possible mechanism. Methods Twenty eight-week-old male db/db mice were randomizedtoi.p. administration of GDF11(0.3mg·kg-1·day-1)or equivalent PBS(n=10)for 6 weeks.10age-matched male db/m were used as normal control, received equivalent PBS injection for 6 weeks. Blood glucose levels, body weights and food intake were monitored weekly. IPGTT and glucose-stimulated insulin secretion ( GSIS) were analyzed. After 6 weeks of intervention, serum HbA1C , TG, TC, and FFA were measured respectively. The concentrations of hormones in serum and pancreas were evaluated. The mRNA expression of Pdx-1, MafA, Nkx6. 1, and insulin2 were determined by RT-PCR. The expression of phosphorylated Smd2 (P-Smad2), Smad2 in islet were examined by western blot. Results Compared with NC group, GDF11 administration decreased FBG, HbA1C , modified lipid profiles. GDF11 improved glucose tolerance and augmented GSIS. Moreover, GDF11 increased serum insulin and pancreatic insulin content, while decreased serum glucagon concentration. The expression of Pdx-1, MafA, Nkx6. 1, and Insulin2 were significantly increased in GDF11 group. GDF11 elevated the expression of P-Smad2 in islets. Conclusion s GDF11 may preserve β-cell function and facilitate the secretion and production of insulin. Diminishing the metabolic abnormalities, alleviating the secretion of glucagon, as well as maintaining the key transcript factor activation may contribute to the amelioration of β-cell function after GDF11 administration. Smad2 pathway may be related to the protective effects of GDF11.