PMID- 32561286 OWN - NLM STAT- MEDLINE DCOM- 20210126 LR - 20211121 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 394 IP - 1 DP - 2020 Sep 1 TI - Insulin exacerbated high glucose-induced epithelial-mesenchymal transition in prostatic epithelial cells BPH-1 and prostate cancer cells PC-3 via MEK/ERK signaling pathway. PG - 112145 LID - S0014-4827(20)30392-X [pii] LID - 10.1016/j.yexcr.2020.112145 [doi] AB - As two most common progressive diseases of aging, type 2 diabetes mellitus (T2DM) and benign prostatic hyperplasia (BPH) were all characterized by endocrine and metabolic disorders. Here, our clinical study showed that there were significant differences in fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance index (HOMA-IR) and prostate volume (PV) between simple BPH patients and BPH complicated with T2DM patients. Further analysis showed that HOMA-IR was positively correlated with PV in BPH complicated with T2DM patients. The in vitro experiment results showed that high glucose (HG) promoted EMT process in a glucose-dependent manner in human prostate hyperplasia cells (BPH-1) and prostate cancer cells (PC-3), and this pathological process was exacerbated by co-culture with insulin. Mechanistically, insulin-induced exacerbation of EMT was depended on the activation of MEK/ERK signaling pathway, and we suggested that insulin and its analogs should be used very carefully for the clinical antihyperglycemic treatment of BPH complicated with T2DM patients. CI - Copyright (c) 2020. Published by Elsevier Inc. FAU - Yang, Tingting AU - Yang T AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Zhou, Yi AU - Zhou Y AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Wang, Haiyan AU - Wang H AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Chen, Shangxiu AU - Chen S AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Shen, Mengli AU - Shen M AD - Department of Pharmacy, The 7th People's Hospital of Zhengzhou, Zhengzhou, 450016, China. FAU - Hu, Yinlu AU - Hu Y AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Wang, Tao AU - Wang T AD - Department of Pharmacy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, China. FAU - Liu, Junjie AU - Liu J AD - Department of Urology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, China. FAU - Jiang, Zhenzhou AU - Jiang Z AD - Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China. FAU - Wang, ZhongJian AU - Wang Z AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Zhu, Xia AU - Zhu X AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Qian, Sitong AU - Qian S AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Yin, Xiaoxing AU - Yin X AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. FAU - Lu, Qian AU - Lu Q AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China. Electronic address: prainry@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200616 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Insulin) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - IY9XDZ35W2 (Glucose) SB - IM EIN - Exp Cell Res. 2021 Dec 15;409(2):112923. PMID: 34801562 MH - Epithelial Cells/drug effects/metabolism MH - Epithelial-Mesenchymal Transition/drug effects/physiology MH - Glucose/*metabolism/*pharmacology MH - Humans MH - Insulin/*pharmacology MH - Insulin Resistance/physiology MH - Male MH - Mitogen-Activated Protein Kinase Kinases MH - Prostate/drug effects/metabolism MH - Prostatic Hyperplasia/*drug therapy/metabolism/pathology MH - Prostatic Neoplasms/drug therapy/metabolism/*pathology MH - Signal Transduction/drug effects OTO - NOTNLM OT - Benign prostatic hyperplasia OT - Epithelial-mesenchymal transition OT - High glucose OT - Insulin OT - MEK/ERK signaling Pathway OT - Type 2 diabetes mellitus EDAT- 2020/06/21 06:00 MHDA- 2021/01/27 06:00 CRDT- 2020/06/21 06:00 PHST- 2020/02/05 00:00 [received] PHST- 2020/05/13 00:00 [revised] PHST- 2020/06/08 00:00 [accepted] PHST- 2020/06/21 06:00 [pubmed] PHST- 2021/01/27 06:00 [medline] PHST- 2020/06/21 06:00 [entrez] AID - S0014-4827(20)30392-X [pii] AID - 10.1016/j.yexcr.2020.112145 [doi] PST - ppublish SO - Exp Cell Res. 2020 Sep 1;394(1):112145. doi: 10.1016/j.yexcr.2020.112145. Epub 2020 Jun 16.