PMID- 33085741 OWN - NLM STAT- MEDLINE DCOM- 20210426 LR - 20210426 IS - 1745-7270 (Electronic) IS - 1672-9145 (Linking) VI - 52 IP - 10 DP - 2020 Oct 19 TI - miR-150 regulates glucose utilization through targeting GLUT4 in insulin-resistant cardiomyocytes. PG - 1111-1119 LID - 10.1093/abbs/gmaa094 [doi] AB - MicroRNAs (miRNAs) play an important role in cardiac function and metabolism. However, whether they regulate insulin resistance (IR) of cardiomyocytes remains unclear. The aim of the present study was to shed light on this issue with a focus on miR-150. We found here that miR-150 level was elevated in myocardium of type 2 diabetes mellitus (T2DM) rat model and in insulin-resistant cardiomyocytes induced by high glucose (25 mM) and high insulin (1 muM). Deregulation of miR-150 downregulated the protein and mRNA levels of glucose transporter 4 (GLUT4) as assessed by western blot, real-time polymerase chain reaction (qPCR), and immunofluorescence assays. Overexpression of miR-150 inhibited glucose utilization in cardiomyocytes as detected by 2-deoxyglucose transport and glucose consumption assays. In contrast, knockdown of miR-150 significantly increased glucose uptake in cardiomyocytes. Moreover, GLUT4 translocation was increased after transfection of miR-150 inhibitor (AMO-150). Collectively, miR-150 reduced glucose utilization by directly decreasing the expression and translocation of GLUT4 in the cardiomyocytes with IR and therefore might be a new therapeutic target for metabolic diseases such as T2DM. CI - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Ju, Jin AU - Ju J AD - Department of Pharmacology, Harbin Medical University (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin 150081, China. FAU - Xiao, Dan AU - Xiao D AD - Department of Pharmacology, Harbin Medical University (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin 150081, China. AD - Department of Psychiatry, Qiqihar Medical University, Qiqihar 161006, China. FAU - Shen, Nannan AU - Shen N AD - Department of Pharmacology, Harbin Medical University (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin 150081, China. AD - Department of Pharmacy (Department of Clinical Medicine), ShaoXing Municipal Hospital, Shaoxing 312000, China. FAU - Zhou, Tong AU - Zhou T AD - Department of Pharmacology, Harbin Medical University (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin 150081, China. AD - Department of Pharmacy, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. FAU - Che, Hui AU - Che H AD - Department of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Li, Xia AU - Li X AD - Department of Pharmacology, Harbin Medical University (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin 150081, China. FAU - Zhang, Shuqian AU - Zhang S AD - Department of Pharmacology, Harbin Medical University (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin 150081, China. FAU - Mokembo, Justine Nyakango AU - Mokembo JN AD - Department of Pharmacology, Harbin Medical University (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin 150081, China. FAU - Jha, Nabanit Kumar AU - Jha NK AD - Department of Pharmacology, Harbin Medical University (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin 150081, China. FAU - Monayo, Seth Mikaye AU - Monayo SM AD - Department of Pharmacology, Harbin Medical University (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin 150081, China. FAU - Wang, Zhiguo AU - Wang Z AD - Department of Pharmacology, Harbin Medical University (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin 150081, China. FAU - Zhang, Yong AU - Zhang Y AD - Department of Pharmacology, Harbin Medical University (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin 150081, China. AD - Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin 150086, China. LA - eng PT - Journal Article PL - China TA - Acta Biochim Biophys Sin (Shanghai) JT - Acta biochimica et biophysica Sinica JID - 101206716 RN - 0 (Glucose Transporter Type 4) RN - 0 (Insulin) RN - 0 (MIRN150 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (Slc2a4 protein, rat) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Animals, Newborn MH - Biological Transport/genetics MH - Diabetes Mellitus, Experimental/genetics/metabolism MH - Glucose/metabolism MH - Glucose Transporter Type 4/genetics/*metabolism MH - Heart/physiopathology MH - Insulin/metabolism MH - Insulin Resistance/*genetics MH - Male MH - MicroRNAs/antagonists & inhibitors/*genetics/*metabolism MH - Myocardium/cytology/metabolism MH - Myocytes, Cardiac/cytology/*metabolism/ultrastructure MH - Primary Cell Culture MH - Rats, Sprague-Dawley OTO - NOTNLM OT - GLUT4 OT - insulin resistance OT - miR-150 OT - type 2 diabetes mellitus EDAT- 2020/10/22 06:00 MHDA- 2021/04/27 06:00 CRDT- 2020/10/21 15:36 PHST- 2020/02/26 00:00 [received] PHST- 2020/07/21 00:00 [revised] PHST- 2020/07/24 00:00 [accepted] PHST- 2020/10/22 06:00 [pubmed] PHST- 2021/04/27 06:00 [medline] PHST- 2020/10/21 15:36 [entrez] AID - 5934597 [pii] AID - 10.1093/abbs/gmaa094 [doi] PST - ppublish SO - Acta Biochim Biophys Sin (Shanghai). 2020 Oct 19;52(10):1111-1119. doi: 10.1093/abbs/gmaa094.