PMID- 34480721
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210929
IS  - 1869-6953 (Print)
IS  - 1869-6961 (Electronic)
IS  - 1869-6961 (Linking)
VI  - 12
IP  - 10
DP  - 2021 Oct
TI  - The Effect of Verapamil on TXNIP Gene Expression, GLP1R mRNA, FBS, HbA1c, and 
      Lipid Profile in T2DM Patients Receiving Metformin and Sitagliptin.
PG  - 2701-2713
LID - 10.1007/s13300-021-01145-4 [doi]
AB  - INTRODUCTION: Type 2 diabetes mellitus (T2DM) is the most common type of 
      diabetes. A decrease in the number of pancreatic beta cells is a pathological 
      sign of diabetes, and to date there is no drug treatment that targets damage to 
      these cells. Pancreatic beta cells have a weak antioxidant system and are highly 
      sensitive to oxidative stress reactions that occur within cells. Thioredoxin 
      interacting protein (TXNIP) inhibits thioredoxin, which is part of the 
      intracellular antioxidant system, thereby accelerating oxidative stress and 
      apoptosis of pancreatic beta cells. Verapamil is a non-dihydropyridine calcium 
      channel blocker. The efficacy of this drug to improve beta cell survival and 
      glucose homeostasis by inhibiting TXNIP expression has been demonstrated in in 
      vitro studies. Although several retrospective studies have shown a lower 
      incidence of T2DM with verapamil treatment, no prospective intervention studies 
      have determined the efficacy of this drug in patients with T2DM. METHODS: The aim 
      of this randomized, double-blind, placebo-controlled study was to evaluate the 
      efficacy and safety of oral verapamil administration in T2DM patients. In this 
      90-day study, the effects of verapamil on fasting blood sugar (FBS), hemoglobin 
      A1C (HbA1c), and the lipid profile were evaluated and compared with those of the 
      placebo. RESULTS: There was a significant decrease in HbA1c (about 0.5%) in the 
      verapamil group at the end of the intervention period. The effects of verapamil 
      on TXNIP gene expression and glucagon-like peptide-1 receptor (GLP1R) mRNA were 
      compared with those of the placebo (at baseline, after 15 and 30 days, and at the 
      end of the study). During the first month of the study, decreased TXNIP gene 
      expression and increased GLP1R mRNA were associated with the administration of 
      verapamil when compared with the placebo, although the differences were not 
      significant. CONCLUSION: Verapamil can lead to better control of T2DM by reducing 
      TXNIP gene expression and increasing beta cell survival and, possibly, by other 
      mechanisms. CLINICAL TRIAL REGISTRATION: IRCT registration no.: 
      IRCT20180417039339N1 ( https://www.IRCT.ir ).
CI  - (c) 2021. The Author(s).
FAU - Malayeri, Alireza
AU  - Malayeri A
AD  - Department of Pharmacology, School of Pharmacy, Ahvaz Jundishapur University of 
      Medical Sciences, Ahvaz, Iran.
FAU - Zakerkish, Mehrnoosh
AU  - Zakerkish M
AD  - Department of Internal Medicine, Diabetes Research Centre, Health Research 
      Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 
      zakerkish-m@ajums.ac.ir.
FAU - Ramesh, Farrokh
AU  - Ramesh F
AD  - Department of Pharmacology, School of Pharmacy, Ahvaz Jundishapur University of 
      Medical Sciences, Ahvaz, Iran.
FAU - Galehdari, Hamid
AU  - Galehdari H
AD  - Department of Genetics, Faculty of Sciences, Shahid Chamran University of Ahvaz, 
      Ahvaz, Iran.
FAU - Hemmati, Ali Asghar
AU  - Hemmati AA
AD  - Medicinal Plant Research Center, School of Pharmacy, Ahvaz Jundishapur University 
      of Medical Sciences, Ahvaz, Iran.
FAU - Angali, Kambiz A
AU  - Angali KA
AD  - Department of Biostatistics and Epidemiology, School of Health, Ahvaz Jundishapur 
      University of Medical Sciences, Ahvaz, Iran.
LA  - eng
PT  - Journal Article
DEP - 20210904
PL  - United States
TA  - Diabetes Ther
JT  - Diabetes therapy : research, treatment and education of diabetes and related 
      disorders
JID - 101539025
PMC - PMC8418290
OTO - NOTNLM
OT  - Randomized controlled trials
OT  - TXNIP
OT  - Type 2 diabetes
OT  - Verapamil
EDAT- 2021/09/05 06:00
MHDA- 2021/09/05 06:01
PMCR- 2021/09/04
CRDT- 2021/09/04 12:12
PHST- 2021/07/15 00:00 [received]
PHST- 2021/08/16 00:00 [accepted]
PHST- 2021/09/05 06:00 [pubmed]
PHST- 2021/09/05 06:01 [medline]
PHST- 2021/09/04 12:12 [entrez]
PHST- 2021/09/04 00:00 [pmc-release]
AID - 10.1007/s13300-021-01145-4 [pii]
AID - 1145 [pii]
AID - 10.1007/s13300-021-01145-4 [doi]
PST - ppublish
SO  - Diabetes Ther. 2021 Oct;12(10):2701-2713. doi: 10.1007/s13300-021-01145-4. Epub 
      2021 Sep 4.