PMID- 24145087
OWN - NLM
STAT- MEDLINE
DCOM- 20140613
LR  - 20200106
IS  - 2299-5684 (Electronic)
IS  - 1734-1140 (Linking)
VI  - 65
IP  - 4
DP  - 2013
TI  - Combination of omeprazole with GLP-1 agonist therapy improves insulin sensitivity 
      and antioxidant activity in liver in type 1 diabetic mice.
PG  - 927-36
AB  - BACKGROUND: Combination with suitable pharmacological agents can improve the 
      antiobesity and antidiabetic actions of glucagon like peptide-1 (GLP-1) based 
      therapies. GLP-1 agonist exendin-4 may have insulin-independent effects on 
      amelioration of insulin resistance and hepatic steatosis by virtue of its action 
      on hepatic GLP-1 receptors, and these effects can be improved by combination with 
      proton pump inhibitors. However, it was not assessed whether omeprazole can 
      improve the peripheral actions of exendin-4 in the state of insulin deficiency. 
      METHODS: We investigated the effects of combination of omeprazole with GLP-1 
      agonist exendin-4 in multiple low-dose streptozotocin (STZ)-induced diabetes in 
      C57BL/KsJ mice, a model of type 1 diabetes. Male diabetic mice were treated with 
      exendin-4 and/or omeprazole for a period of 4 weeks. RESULTS: Omeprazole 
      treatment had no significant effect on lowering the blood glucose levels of 
      diabetic mice, when compared to control, although it improved the 
      antihyperglycemic actions of exendin-4. Similarly, serum triglycerides and total 
      cholesterols levels were significantly lower in the combination treated mice 
      compared to either exendin-4 and omeprazole alone. In addition, the combination 
      treatment significantly ameliorated lipid peroxidation and hepatic triglycerides 
      in diabetic mice compared to either exendin-4 and omeprazole alone. The 
      improvement in hepatic insulin sensitivity, as indicated by insulin tolerance 
      test (ITT) and pyruvate tolerance test (IPPTT), was correlated with the 
      expression of nuclear factor erythroid-related factor 2 (Nrf2) and insulin 
      receptor substrate-1 (IRS-1) and the combination treatment significantly improved 
      the insulin sensitivity in comparison to vehicle control. CONCLUSION: We conclude 
      that combination with omeprazole improves the insulin sensitizing actions of 
      GLP-1 therapy and these effects are partially mediated through the decrease in 
      hepatic steatosis and improvement in antioxidant status in the liver.
FAU - Patel, Vishal
AU  - Patel V
AD  - Department of Pharmacology and Toxicology, Zydus Research Centre, Cadila 
      Healthcare Limited, Sarkhej-Bavla N.H. No.8A, Moraiya, Ahmedabad 382210, India. 
      amitjoharapurkar@zyduscadila.com.
FAU - Joharapurkar, Amit
AU  - Joharapurkar A
FAU - Dhanesha, Nirav
AU  - Dhanesha N
FAU - Kshirsagar, Samadhan
AU  - Kshirsagar S
FAU - Detroja, Jaysukh
AU  - Detroja J
FAU - Patel, Kartikkumar
AU  - Patel K
FAU - Gandhi, Tejal
AU  - Gandhi T
FAU - Patel, Kirti
AU  - Patel K
FAU - Bahekar, Rajesh
AU  - Bahekar R
FAU - Jain, Mukul
AU  - Jain M
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Pharmacol Rep
JT  - Pharmacological reports : PR
JID - 101234999
RN  - 0 (Antioxidants)
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, mouse)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Peptides)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0 (Venoms)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9P1872D4OL (Exenatide)
RN  - KG60484QX9 (Omeprazole)
SB  - IM
MH  - Animals
MH  - Antioxidants/*metabolism
MH  - Blood Glucose/drug effects
MH  - Diabetes Mellitus, Experimental/*drug therapy/*metabolism
MH  - Drug Therapy, Combination
MH  - Exenatide
MH  - Glucagon-Like Peptide 1/*agonists
MH  - Hypoglycemic Agents/pharmacology/therapeutic use
MH  - Insulin Receptor Substrate Proteins/metabolism
MH  - Insulin Resistance
MH  - Liver/*drug effects/metabolism
MH  - Male
MH  - Mice
MH  - NF-E2-Related Factor 2/metabolism
MH  - Omeprazole/*pharmacology/therapeutic use
MH  - Peptides/*pharmacology/therapeutic use
MH  - Proton Pump Inhibitors/pharmacology/therapeutic use
MH  - Venoms/*pharmacology/therapeutic use
EDAT- 2013/10/23 06:00
MHDA- 2014/06/15 06:00
CRDT- 2013/10/23 06:00
PHST- 2012/09/06 00:00 [received]
PHST- 2013/02/05 00:00 [revised]
PHST- 2013/10/23 06:00 [entrez]
PHST- 2013/10/23 06:00 [pubmed]
PHST- 2014/06/15 06:00 [medline]
AID - S1734-1140(13)71074-0 [pii]
AID - 10.1016/s1734-1140(13)71074-0 [doi]
PST - ppublish
SO  - Pharmacol Rep. 2013;65(4):927-36. doi: 10.1016/s1734-1140(13)71074-0.