BACKGROUND: Epidemiological evidence has indicated that vitamin D deficiency increased the risk of insulin resistance in metabolic syndrome. The present study was conducted to test the hypothesis that 1,25-dihydroxyvitamin D may improve the free fatty-acid (FFA)-induced insulin resistance in muscle cells. METHOD: The insulin resistance of muscle cell model was established by treatment of FFA in differentiated C2C12 cells. Glucose uptake of C2C12 myotubes was analysed by the 3H-labelled 2-deoxyglucose uptake assay. The diameter of myotubes was measured under the condition of glutaraldehyde-induced autofluorescense. Tyrosine phosphorylated insulin receptor substrate 1 (IRS-1) was measured by immunoprecipitation. Serine phosphorylated IRS-1 and protein kinase B (Akt), extracellular signal-related kinase (ERK), c-Jun amino-terminal kinases (JNK) as well as their phosphorylated form were analysed by Western blots. RESULTS: Compared with a vehicle-treated group, FFA treatment in myotubes was associated with 70.6% reduction in insulin-mediated uptake of glucose, a five-fold increase in serine phosphorylation of IRS-1, 76.9% decrease in tyrosine phosphorylation of IRS-1 and 81.8% decrease in phosphorylation of Akt. Supplement of 1,25-dihydroxyvitamin D improved the FFA-induced inhibition of glucose uptake in a dose- dependent (p < 0.001) and time-dependent manner (p < 0.01). This was accompanied by increase in tyrosine phosphorylation of IRS-1 and phosphorylated Akt and decrease in serine phosphorylation of IRS-1 (p < 0.001). 1,25-Dihydroxyvitamin D also inhibited the FFA-induced reduction in myotube diameter by 35.3% (p < 0.001). JNK phosphorylation was reduced by 126.7% with treatment of 1,25-dihydroxyvitamin D (p < 0.001). 1,25-Dihydroxyvitamin D had no effect on FFA-induced ERK phosphorylation (p = 0.84). CONCLUSION: 1,25-Dihydroxyvitamin D improved the FFA-induced insulin resistance in muscle cells.
BACKGROUND: Epidemiological evidence has indicated that vitamin D deficiency increased the risk of insulin resistance in metabolic syndrome. The present study was conducted to test the hypothesis that 1,25-dihydroxyvitamin D may improve the free fatty-acid (FFA)-induced insulin resistance in muscle cells. METHOD: The insulin resistance of muscle cell model was established by treatment of FFA in differentiated C2C12 cells. Glucose uptake of C2C12 myotubes was analysed by the 3H-labelled 2-deoxyglucose uptake assay. The diameter of myotubes was measured under the condition of glutaraldehyde-induced autofluorescense. Tyrosine phosphorylated insulin receptor substrate 1 (IRS-1) was measured by immunoprecipitation. Serine phosphorylated IRS-1 and protein kinase B (Akt), extracellular signal-related kinase (ERK), c-Jun amino-terminal kinases (JNK) as well as their phosphorylated form were analysed by Western blots. RESULTS: Compared with a vehicle-treated group, FFA treatment in myotubes was associated with 70.6% reduction in insulin-mediated uptake of glucose, a five-fold increase in serine phosphorylation of IRS-1, 76.9% decrease in tyrosine phosphorylation of IRS-1 and 81.8% decrease in phosphorylation of Akt. Supplement of 1,25-dihydroxyvitamin D improved the FFA-induced inhibition of glucose uptake in a dose- dependent (p < 0.001) and time-dependent manner (p < 0.01). This was accompanied by increase in tyrosine phosphorylation of IRS-1 and phosphorylated Akt and decrease in serine phosphorylation of IRS-1 (p < 0.001). 1,25-Dihydroxyvitamin D also inhibited the FFA-induced reduction in myotube diameter by 35.3% (p < 0.001). JNK phosphorylation was reduced by 126.7% with treatment of 1,25-dihydroxyvitamin D (p < 0.001). 1,25-Dihydroxyvitamin D had no effect on FFA-induced ERK phosphorylation (p = 0.84). CONCLUSION:1,25-Dihydroxyvitamin D improved the FFA-induced insulin resistance in muscle cells.
Authors: Samar R El Khoudary; Saad Samargandy; Irfan Zeb; Temitope Foster; Ian H de Boer; Dong Li; Matthew J Budoff Journal: Nutr Metab Cardiovasc Dis Date: 2019-09-10 Impact factor: 4.222
Authors: Giuseppe Saggese; Francesco Vierucci; Flavia Prodam; Fabio Cardinale; Irene Cetin; Elena Chiappini; Gian Luigi De' Angelis; Maddalena Massari; Emanuele Miraglia Del Giudice; Michele Miraglia Del Giudice; Diego Peroni; Luigi Terracciano; Rino Agostiniani; Domenico Careddu; Daniele Giovanni Ghiglioni; Gianni Bona; Giuseppe Di Mauro; Giovanni Corsello Journal: Ital J Pediatr Date: 2018-05-08 Impact factor: 2.638
Authors: Cristiana Catena; Chiara Cosma; Valentina Camozzi; Mario Plebani; Mario Ermani; Leonardo A Sechi; Francesco Fallo Journal: High Blood Press Cardiovasc Prev Date: 2013-04-13
Authors: Lisa Ceglia; Sathit Niramitmahapanya; Mauricio da Silva Morais; Donato A Rivas; Susan S Harris; Heike Bischoff-Ferrari; Roger A Fielding; Bess Dawson-Hughes Journal: J Clin Endocrinol Metab Date: 2013-10-09 Impact factor: 5.958
Authors: Lisa Ceglia; Donato A Rivas; Rachele M Pojednic; Lori Lyn Price; Susan S Harris; Donald Smith; Roger A Fielding; Bess Dawson-Hughes Journal: Endocrine Date: 2013-05-11 Impact factor: 3.633
Authors: Ling Lu; Zhijie Yu; An Pan; Frank B Hu; Oscar H Franco; Huaixing Li; Xiaoying Li; Xilin Yang; Yan Chen; Xu Lin Journal: Diabetes Care Date: 2009-04-14 Impact factor: 17.152