Melatonin rescues 3T3-L1 adipocytes from FFA-induced insulin resistance by inhibiting phosphorylation of IRS-1 on Ser307.
Melatonin is biosynthesized in the pineal gland and secreted into the bloodstream. Evidences indicate a role of melatonin in the regulation of glucose metabolism. The objective of this study was to investigate the effect of melatonin on insulin sensitivity in insulin resistant adipocytes. Following a preincubation with melatonin or vehicle for 30 min, insulin resistant cells of 3T3-L1 adipocytes were induced by palmitic acids (300 μM, 6 h). Our results showed that palmitic acids inhibited both the basal and insulin-stimulated uptake of [(3)H]-2-Deoxyglucose, down-regulated the levels of IRS-1 and GLUT-4. However, compared to the vehicle group, melatonin pre-treatment increased significantly the uptake of [(3)H]-2-Deoxyglucose as well as the level of GLUT-4, and decreased phosphorylated IRS-1 (Ser307) although total IRS-1 did not change significantly. These data suggest that palmitic acids impair insulin signal via down-regulating the expressions of IRS-1 and GLUT-4; whereas melatonin can ameliorate insulin sensitivity by inhibiting Ser307 phosphorylation in IRS-1 and increasing GLUT-4 expressions in insulin resistant 3T3-L1 adipocytes. We conclude that melatonin regulates the insulin sensitivity and glucose homeostasis via inhibiting Ser-phosphorylation and improving function of IRS-1.
Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, China; Department of Biochemistry and Molecular Biology, University of South China, Hengyang, China.
Meihua
M
She
Department of Biochemistry and Molecular Biology, University of South China, Hengyang, China.
Hongjie
H
Hou
Department of Laboratory Animal Science, University of South China, Hengyang, China.
Zongbao
Z
Wang
Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, China.
Chi
C
Zhang
Drug Discovery, Neurim Pharmaceuticals Ltd., Tel-Aviv, Israel.
Moshe
M
Laudon
Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, China; Department of Biochemistry and Molecular Biology, University of South China, Hengyang, China. Electronic address: wdy20042004@126.com.
Weidong
W
Yin
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000737:chemistry / Q000378:metabolism*; D007333:Insulin Resistance; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D019308:Palmitic Acid / Q000009:adverse effects*; D010766:Phosphorylation / Q000187:drug effects; D012694:Serine / Q000378:metabolism*
D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D019308:Palmitic Acid; D012694:Serine; D005947:Glucose; D008550:Melatonin
3T3-L1 adipocytes; Glucose uptake; Insulin sensitivity; Melatonin