PMID- 23845213
OWN - NLM
STAT- MEDLINE
DCOM- 20140506
LR  - 20130902
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 714
IP  - 1-3
DP  - 2013 Aug 15
TI  - The combined effect of metformin and L-cysteine on inflammation, oxidative stress 
      and insulin resistance in streptozotocin-induced type 2 diabetes in rats.
PG  - 448-55
LID - S0014-2999(13)00512-8 [pii]
LID - 10.1016/j.ejphar.2013.07.002 [doi]
AB  - Increasing evidence has established causative links between obesity, chronic 
      inflammation and insulin resistance; the core pathophysiological feature in type 
      2 diabetes mellitus. This study was designed to examine whether the combination 
      of L-cysteine and metformin would provide additional benefits in reducing 
      oxidative stress, inflammation and insulin resistance in streptozotocin-induced 
      type 2 diabetes in rats. Male Wistar rats were fed a high-fat diet (HFD) for 8 
      weeks to induce insulin resistance after which they were rendered diabetic with 
      low-dose streptozotocin. Diabetic rats were treated with metformin (300 
      mg/kg/day), L-cysteine (300 mg/kg/day) and their combination along with HFD for 
      another 2 weeks. Control rats were fed normal rat chow throughout the experiment. 
      At the end of treatment, fasting blood glucose, fasting serum insulin, 
      homeostasis model assessment-insulin resistance index (HOMA-IR) and serum free 
      fatty acids (FFAs) were measured. Serum levels of the inflammatory markers; 
      monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP) and 
      nitrite/nitrate were also determined. The liver was isolated and used for 
      determination of malondialdehyde (MDA), reduced glutathione (GSH), caspase-3 and 
      cytochrome c levels. The hypoglycemic effect of the combination therapy exceeded 
      that of metformin and L-cysteine monotherapies with more improvement in insulin 
      resistance. All treated groups exhibited significant reductions in serum FFAs, 
      oxidative stress and inflammatory parameters, caspase-3 and cytochrome c levels 
      compared to untreated diabetic rats with the highest improvement observed in the 
      combination group. In conclusion, the present results clearly suggest that 
      L-cysteine can be strongly considered as an adjunct to metformin in management of 
      type 2 diabetes.
CI  - (c) 2013 Elsevier B.V. All rights reserved.
FAU - Salman, Zenat K
AU  - Salman ZK
AD  - Medical Research Institute, University of Alexandria, 165 Horreya Avenue, 
      Alexandria, Egypt.
FAU - Refaat, Rowaida
AU  - Refaat R
FAU - Selima, Eman
AU  - Selima E
FAU - El Sarha, Ashgan
AU  - El Sarha A
FAU - Ismail, Menna A
AU  - Ismail MA
LA  - eng
PT  - Journal Article
DEP - 20130709
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Chemokine CCL2)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - 9007-43-6 (Cytochromes c)
RN  - 9100L32L2N (Metformin)
RN  - EC 3.4.22.- (Caspase 3)
RN  - GAN16C9B8O (Glutathione)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Animals
MH  - Body Weight/drug effects
MH  - C-Reactive Protein/metabolism
MH  - Caspase 3/metabolism
MH  - Chemokine CCL2/blood
MH  - Cysteine/*pharmacology/therapeutic use
MH  - Cytochromes c/metabolism
MH  - Diabetes Mellitus, Experimental/blood/*drug therapy/metabolism/pathology
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy/metabolism/pathology
MH  - Drug Interactions
MH  - Fatty Acids, Nonesterified/blood
MH  - Glutathione/metabolism
MH  - Inflammation/drug therapy
MH  - *Insulin Resistance
MH  - Liver/drug effects/metabolism/pathology
MH  - Male
MH  - Malondialdehyde/metabolism
MH  - Metformin/*pharmacology/therapeutic use
MH  - Nitrates/blood
MH  - Nitrites/blood
MH  - Oxidative Stress/*drug effects
MH  - Rats
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Insulin resistance
OT  - Metformin
OT  - Streptozotocin-induced type 2 diabetes
OT  - l-Cysteine
EDAT- 2013/07/13 06:00
MHDA- 2014/05/07 06:00
CRDT- 2013/07/13 06:00
PHST- 2013/02/02 00:00 [received]
PHST- 2013/05/20 00:00 [revised]
PHST- 2013/07/01 00:00 [accepted]
PHST- 2013/07/13 06:00 [entrez]
PHST- 2013/07/13 06:00 [pubmed]
PHST- 2014/05/07 06:00 [medline]
AID - S0014-2999(13)00512-8 [pii]
AID - 10.1016/j.ejphar.2013.07.002 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2013 Aug 15;714(1-3):448-55. doi: 10.1016/j.ejphar.2013.07.002. 
      Epub 2013 Jul 9.