PMID- 35106626
OWN - NLM
STAT- MEDLINE
DCOM- 20220406
LR  - 20220531
IS  - 1432-1912 (Electronic)
IS  - 0028-1298 (Linking)
VI  - 395
IP  - 4
DP  - 2022 Apr
TI  - Long-term GABA administration improves FNDC5, TFAM, and UCP3 mRNA expressions in 
      the skeletal muscle and serum irisin levels in chronic type 2 diabetic rats.
PG  - 417-428
LID - 10.1007/s00210-022-02211-9 [doi]
AB  - In this study, we aimed to investigate whether the anti-diabetic effects of 
      gamma-aminobutyric acid (GABA) and insulin can be mediated through the regulation of 
      gene expression related to irisin production and mitochondrial biogenesis in type 
      2 diabetic mellitus (T2DM) rats. Four groups (n = 6) were used in this study: 
      control, T2DM, T2DM + insulin, and T2DM + GABA groups. After T2DM induction for 
      3 months (high-fat diet + 35 mg/kg streptozotocin) and treatment with GABA or 
      insulin for 3 months, circulating levels of FBG, triglyceride, LDL, Ox-LDL, and 
      insulin as well as hepatic and serum irisin levels were measured. The mRNA 
      expressions of fibronectin type III domain-containing protein 5 (FNDC5), 
      mitochondrial transcription factor A (TFAM), and mitochondrial uncoupling protein 
      3 (UCP3) were also evaluated in the skeletal muscle of all groups. GABA therapy 
      improved the FBG and insulin levels in diabetic rats. Insulin treatment 
      significantly reduced FBG and failed to maintain glucose close to the control 
      level. Insulin or GABA therapy significantly decreased the levels of LDL, Ox-LDL, 
      and HOMA-IR index. Circulating irisin levels were markedly decreased in 
      insulin-treated group, while irisin levels did not show significant changes in 
      GABA-treated group compared with control group. GABA or insulin therapy increased 
      mRNA expressions of TFAM and UCP3 in diabetic rats. GABA therapy also led to a 
      significant increase in FNDC5 mRNA. Our findings suggest that the anti-diabetic 
      effect of GABA may be mediated, in part, by a decrease in Ox-LDL levels and an 
      increase in the levels of irisin as well as FNDC5, TFAM, and UCP3 gene expression 
      in T2DM rats.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Yazdanimoghaddam, Farzaneh
AU  - Yazdanimoghaddam F
AD  - Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical 
      Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
FAU - Ghasemi, Maedeh
AU  - Ghasemi M
AD  - Department of Physiology, School of Medicine, Isfahan University of Medical 
      Sciences, Isfahan, Iran.
FAU - Teamparvar, Hanif
AU  - Teamparvar H
AD  - School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical 
      Sciences, Isfahan, Iran.
FAU - Soltani, Nepton
AU  - Soltani N
AD  - Department of Physiology, School of Medicine, Isfahan University of Medical 
      Sciences, Isfahan, Iran.
FAU - Aghaei, Mahmoud
AU  - Aghaei M
AD  - Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical 
      Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
FAU - Rezazadeh, Hossein
AU  - Rezazadeh H
AD  - Department of Physiology, School of Medicine, Isfahan University of Medical 
      Sciences, Isfahan, Iran.
FAU - Zadhoush, Fouzieh
AU  - Zadhoush F
AUID- ORCID: 0000-0002-2093-6610
AD  - Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical 
      Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. 
      f.zadhoush@pharm.mui.ac.ir.
LA  - eng
PT  - Journal Article
DEP - 20220202
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (FNDC5 protein, rat)
RN  - 0 (Fibronectins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tfam protein, rat)
RN  - 0 (Transcription Factors)
RN  - 0 (Ucp3 protein, rat)
RN  - 0 (Uncoupling Protein 3)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Experimental/drug therapy/metabolism
MH  - Diabetes Mellitus, Type 2
MH  - *Fibronectins/blood
MH  - Muscle, Skeletal/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - *Transcription Factors/genetics/metabolism
MH  - *Uncoupling Protein 3/genetics/metabolism
MH  - *gamma-Aminobutyric Acid/pharmacology
OTO - NOTNLM
OT  - FNDC5
OT  - GABA
OT  - Insulin resistance
OT  - Irisin
OT  - TFAM
OT  - Type 2 diabetes mellitus
OT  - UCP3
EDAT- 2022/02/03 06:00
MHDA- 2022/04/07 06:00
CRDT- 2022/02/02 05:36
PHST- 2021/11/24 00:00 [received]
PHST- 2022/01/24 00:00 [accepted]
PHST- 2022/02/03 06:00 [pubmed]
PHST- 2022/04/07 06:00 [medline]
PHST- 2022/02/02 05:36 [entrez]
AID - 10.1007/s00210-022-02211-9 [pii]
AID - 10.1007/s00210-022-02211-9 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2022 Apr;395(4):417-428. doi: 
      10.1007/s00210-022-02211-9. Epub 2022 Feb 2.