PMID- 37944441
OWN - NLM
STAT- MEDLINE
DCOM- 20231207
LR  - 20231217
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 169
DP  - 2023 Dec 31
TI  - Effects of dapagliflozin monotherapy and combined aerobic exercise on skeletal 
      muscle mitochondrial quality control and insulin resistance in type 2 diabetes 
      mellitus rats.
PG  - 115852
LID - S0753-3322(23)01650-5 [pii]
LID - 10.1016/j.biopha.2023.115852 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is a prevalent, chronic metabolic disease. 
      Sodium-glucose cotransporter-2 (SGLT2) inhibitors and aerobic exercise (AE) have 
      shown promise in mitigating insulin resistance (IR) and T2DM. This study 
      investigated the effects of dapagliflozin (Dapa) monotherapy and combined AE on 
      mitochondrial quality control (MQC) in skeletal muscle and IR in T2DM rats. T2DM 
      rats, induced by a high-fat diet/streptozotocin model, were randomly assigned to 
      the following groups: T2DM+vehicle group (DMV), T2DM rats treated with Dapa 
      (DMDa, 10 mg/kg/d), T2DM rats subjected to combined Dapa treatment and AE 
      (DMDa+AE), and the standard control group (CON). Blood and skeletal muscle 
      samples were collected after 6 weeks of intragastric administration and treadmill 
      exercise. The results showed that DMDa monotherapy could reduce the accumulation 
      of white adipose tissue and skeletal muscle lipid droplets and improve HOMA-IR. 
      While the combined AE led to further reductions in subcutaneous white adipose 
      tissue and fasting glucose levels, it did not confer additional benefits in terms 
      of HOMA-IR. Furthermore, Dapa monotherapy enhanced skeletal muscle mitochondrial 
      biogenesis (PGC-1alpha, NRF1, TFAM, and COX IV), mitochondrial dynamics (OPA1, DRP1, 
      and MFN2), and mitophagy (PGAM5 and PINK1) related protein levels. Nevertheless, 
      the combination of Dapa with AE treatment did not yield an additive effect. In 
      conclusion, this study highlights the potential of SGLT2 inhibitors, specifically 
      Dapa, in ameliorating IR and maintaining MQC in skeletal muscle in rats with 
      T2DM. However, combined AE did not produce an additive effect, indicating the 
      need for further research.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Zhang, Liangzhi
AU  - Zhang L
AD  - Exercise and Metabolism Research Center, College of Physical Education and Health 
      Sciences, Zhejiang Normal University, Jinhua, Zhejiang, China.
FAU - Lin, Hengjun
AU  - Lin H
AD  - Department of Colorectal anal Surgery, Jinhua People's Hospital, Jinhua, 
      Zhejiang, China.
FAU - Yang, Xudong
AU  - Yang X
AD  - Exercise and Metabolism Research Center, College of Physical Education and Health 
      Sciences, Zhejiang Normal University, Jinhua, Zhejiang, China.
FAU - Shi, Jipeng
AU  - Shi J
AD  - Exercise Capacity Assessment and Promotion Research Center, School of Physical 
      Education, Northeast Normal University, Changchun, Jilin, China.
FAU - Sheng, Xiusheng
AU  - Sheng X
AD  - Medical Molecular Biology Laboratory, School of Medicine, Jinhua Polytechnic, 
      Jinhua, Zhejiang, China.
FAU - Wang, Lifeng
AU  - Wang L
AD  - Exercise and Metabolism Research Center, College of Physical Education and Health 
      Sciences, Zhejiang Normal University, Jinhua, Zhejiang, China.
FAU - Li, Ting
AU  - Li T
AD  - Exercise and Metabolism Research Center, College of Physical Education and Health 
      Sciences, Zhejiang Normal University, Jinhua, Zhejiang, China.
FAU - Quan, Helong
AU  - Quan H
AD  - Exercise Capacity Assessment and Promotion Research Center, School of Physical 
      Education, Northeast Normal University, Changchun, Jilin, China. Electronic 
      address: quanhelong@nenu.edu.cn.
FAU - Zhai, Xia
AU  - Zhai X
AD  - Medical Molecular Biology Laboratory, School of Medicine, Jinhua Polytechnic, 
      Jinhua, Zhejiang, China. Electronic address: 20211049@jhc.edu.cn.
FAU - Li, Wei
AU  - Li W
AD  - Exercise and Metabolism Research Center, College of Physical Education and Health 
      Sciences, Zhejiang Normal University, Jinhua, Zhejiang, China. Electronic 
      address: ty1986@zjnu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20231107
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 1ULL0QJ8UC (dapagliflozin)
RN  - 0 (Blood Glucose)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Insulin Resistance/physiology
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - Blood Glucose/metabolism
MH  - Muscle, Skeletal
OTO - NOTNLM
OT  - Aerobic exercise
OT  - Dapagliflozin
OT  - Insulin resistance
OT  - Mitochondrial quality control
OT  - Skeletal muscle
OT  - Type 2 diabetes mellitus
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/11/10 00:44
MHDA- 2023/12/07 12:42
CRDT- 2023/11/09 18:15
PHST- 2023/09/08 00:00 [received]
PHST- 2023/10/31 00:00 [revised]
PHST- 2023/11/05 00:00 [accepted]
PHST- 2023/12/07 12:42 [medline]
PHST- 2023/11/10 00:44 [pubmed]
PHST- 2023/11/09 18:15 [entrez]
AID - S0753-3322(23)01650-5 [pii]
AID - 10.1016/j.biopha.2023.115852 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2023 Dec 31;169:115852. doi: 10.1016/j.biopha.2023.115852. 
      Epub 2023 Nov 7.