Melatonin-Mediated Intracellular Insulin during 2-Deoxy-d-glucose Treatment Is Reduced through Autophagy and EDC3 Protein in Insulinoma INS-1E Cells

• Published in: Oxidative medicine and cellular longevity Vol. 2016; no. 2016; pp. 1 - 11
• Main Authors: Kim, Han Sung, Yoo, Yeong-Min, Han, Tae-Young
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2016; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Autophagy; Biosynthesis; Biotechnology; Comparative analysis; Deoxyglucose - metabolism; Dextrose; Diabetes; Diabetes therapy; Endoplasmic reticulum; Glucose; Insulin; Insulin - metabolism; Insulin resistance; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - metabolism; Insulinoma - metabolism; Kinases; Melatonin; Melatonin - pharmacology; Metabolic disorders; Phosphorylation; Proteins; Regulation; Ribonucleoproteins, Small Nuclear - genetics; Ribonucleoproteins, Small Nuclear - metabolism; Studies; Superoxide; Type 2 diabetes
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2016/2594703

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.