PMID- 37935388 OWN - NLM STAT- MEDLINE DCOM- 20231211 LR - 20231216 IS - 1439-3646 (Electronic) IS - 0947-7349 (Print) IS - 0947-7349 (Linking) VI - 131 IP - 12 DP - 2023 Dec TI - Vitamin D Alleviates Type 2 Diabetes Mellitus by Mitigating Oxidative Stress-Induced Pancreatic beta-Cell Impairment. PG - 656-666 LID - 10.1055/a-2191-9969 [doi] AB - OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a common metabolic disorder with rising incidence worldwide. This study explored the anti-T2DM role of vitamin D, thereby providing novel therapeutic strategies. METHODS: C57BL/6 J mice and MIN6 cells were used to induce in vivo T2DM and damaged beta-cell models, respectively. Body weights, fasting blood glucose, and fasting insulin were measured in mice. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted on mice. Lipid indices (TG, TC, LDL-C, and HDL-C) were detected in mouse serum. Hematoxylin-eosin staining was used to evaluate pancreatic tissue injury. ELISA was used to assess insulin and oxidative stress (OS) markers (MDA, GSH, and SOD) in mice and MIN6 cells. Production of ROS was detected in islet beta-cells and MIN6 cells. Cell viability and apoptosis were evaluated using CCK-8 and flow cytometry, respectively. QRT-PCR and western blotting were used to detect pro-inflammatory factors (TNF-alpha and IL-6) and endoplasmic reticulum stress (ERS) markers (CHOP and GRP78), respectively. RESULTS: Vitamin D reduced body weights, fasting blood glucose, and insulin and ameliorated glucose tolerance and insulin sensitivity in T2DM mice. Besides, vitamin D decreased serum TG, TC, LDL-C, and increased HDL-C in T2DM mice. Vitamin D inhibited pancreatic histopathological injury, cell apoptosis, OS, and beta-cell decline in T2DM mice. Moreover, vitamin D alleviated cell death, insufficient insulin secretion, inflammation, OS, and ERS in damaged MIN6 cells. Notably, N-acetyl-L-cysteine (an OS inhibitor) enhanced these effects of vitamin D. CONCLUSIONS: Vitamin D relieved T2DM symptoms by alleviating OS-induced beta-cell impairment. CI - The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/). FAU - Liu, Jia AU - Liu J AD - Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, Gansu, China. FAU - Zhang, Yuanjun AU - Zhang Y AD - Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, Gansu, China. FAU - Shi, Derong AU - Shi D AD - Gansu University of Chinese Medicine, Gansu, China. FAU - He, Cuihuan AU - He C AD - Gansu University of Chinese Medicine, Gansu, China. FAU - Xia, Guanghao AU - Xia G AD - Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, Gansu, China. LA - eng PT - Journal Article DEP - 20231107 PL - Germany TA - Exp Clin Endocrinol Diabetes JT - Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association JID - 9505926 RN - 0 (Blood Glucose) RN - 1406-16-2 (Vitamin D) RN - 0 (Cholesterol, LDL) RN - 0 (Insulin) SB - IM MH - Mice MH - Animals MH - *Diabetes Mellitus, Type 2/metabolism MH - Blood Glucose/metabolism MH - Vitamin D/pharmacology/therapeutic use MH - Cholesterol, LDL MH - Mice, Inbred C57BL MH - Insulin MH - *Insulin-Secreting Cells/metabolism MH - Oxidative Stress MH - Body Weight PMC - PMC10700019 COIS- The authors declare that they have no conflict of interest. EDAT- 2023/11/08 00:42 MHDA- 2023/12/11 12:42 PMCR- 2023/11/01 CRDT- 2023/11/07 19:22 PHST- 2023/12/11 12:42 [medline] PHST- 2023/11/08 00:42 [pubmed] PHST- 2023/11/07 19:22 [entrez] PHST- 2023/11/01 00:00 [pmc-release] AID - eced06-2023-0182-dia [pii] AID - 10.1055/a-2191-9969 [doi] PST - ppublish SO - Exp Clin Endocrinol Diabetes. 2023 Dec;131(12):656-666. doi: 10.1055/a-2191-9969. Epub 2023 Nov 7.