title: Melatonin-Mediated Intracellular Insulin during 2-Deoxy-d-glucose Treatment Is Reduced through Autophagy and EDC3 Protein in Insulinoma INS-1E Cells.
abstract: 2-DG triggers glucose deprivation without altering other nutrients or metabolic pathways and then activates autophagy via activation of AMPK and endoplasmic reticulum (ER) stress. We investigated whether 2-DG reduced intracellular insulin increased by melatonin via autophagy/EDC3 in insulinoma INS-1E cells. p-AMPK and GRP78/BiP level were significantly increased by 2-DG in the presence/absence of melatonin, but IRE1α level was reduced in 2-DG treatment. Levels of p85α, p110, p-Akt (Ser473, Thr308), and p-mTOR (Ser2481) were also significantly reduced by 2-DG in the presence/absence of melatonin. Mn-SOD increased with 2-DG plus melatonin compared to groups treated with/without melatonin alone. Bcl-2 was decreased and Bax increased with 2-DG plus melatonin. LC3II level increased with 2-DG treatment in the presence/absence of melatonin. Intracellular insulin production increased in melatonin plus 2-DG but reduced in treatment with 2-DG with/without melatonin. EDC3 was increased by 2-DG in the presence/absence of melatonin. Rapamycin, an mTOR inhibitor, increased GRP78/BiP and EDC3 levels in a dose-dependent manner and subsequently resulted in a decrease in intracellular production of insulin. These results suggest that melatonin-mediated insulin synthesis during 2-DG treatment involves autophagy and EDC3 protein in rat insulinoma INS-1E cells and subsequently results in a decrease in intracellular production of insulin.
authors: Department of Biomedical Engineering, Yonsei-Fraunhofer Medical Device Laboratory, Yonsei University, Wonju, Gangwon-do 26493, Republic of Korea.
authors: Han Sung
authors: HS
authors: Kim
authors: Fraunhofer Institute IKTS-MD, Maria-Reiche-Straße 2, 01109 Dresden, Germany.
authors: Tae-Young
authors: TY
authors: Han
authors: Department of Biomedical Engineering, Yonsei-Fraunhofer Medical Device Laboratory, Yonsei University, Wonju, Gangwon-do 26493, Republic of Korea.
authors: Yeong-Min
authors: 0000-0003-1732-8494
authors: YM
authors: Yoo
mesh_terms: D001343:Autophagy; D003847:Deoxyglucose / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D007340:Insulinoma / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics* / Q000378:metabolism*
chemical_list: C525042:EDC3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D007328:Insulin; D017411:Ribonucleoproteins, Small Nuclear; D003847:Deoxyglucose; D008550:Melatonin