title: Gemfibrozil and its combination with metformin on pleiotropic effect on IL-10 and adiponectin and anti-atherogenic treatment in insulin resistant type 2 diabetes mellitus rats.
abstract: OBJECTIVE
  Gemfibrozil is a PPAR-α ligand that inhibits the progression of atherosclerosis in insulin resistance type 2 diabetes mellitus (IR type 2 DM). Gemfibrozil, poor anti-hyperglycemic combined with metformin, evaluated for MMP-9, IL-10 and adiponectin beyond glycemic control.
  IR type 2 DM induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rat model. IR type 2 DM rats at 6-week age treated for 8 weeks with (1) gemfibrozil (140 mg/kg od) and (2) gemfibrozil (70 mg/kg bid) + metformin (60 mg/kg bid). At the end, risk parameters like MMP-9, IL-10 and adiponectin were evaluated by ELISA kits.
  
  
  RESULTS
  Gemfibrozil reduced the MMP-9 levels (-25.740 %) (106.772 ± 7.201 ng/ml vs. 80.231 ± 7.023 ng/ml, P < 0.01); increased adiponectin (68.321 %) (8.781 ± 1.111 μg/ml vs. 14.782 ± 1.055 μg/ml) and IL-10 (155.687 %) (334.208 ± 26.307 pg/ml vs. 853.472 ± 23.172 pg/ml, P < 0.001), but poor glycemic control (-6.169 %) (167.5 ± 16.037 vs. 157.167 ± 3.911, P = ns), hence combined with metformin showed synergistic activity, reduced the MMP-9 levels (-16.992 %) (106.772 ± 7.201 ng/ml vs. 89.941 ± 8.636 ng/ml, P < 0.05) and increased adiponectin (39.870 %) (8.781 ± 1.111 μg/ml vs. 12.282 ± 0.782 μg/ml) and, IL-10 (80.136 %) (334.208 ± 26.307 pg/ml vs. 602.029 ± 39.668 pg/ml, P < 0.01) had good glycemic control (-28.856 %) (167.5 ± 16.037 mg/dl vs. 129.167 ± 4.214 mg/dl, P < 0.05).
  
  
  CONCLUSIONS
  Gemfibrozil plus metformin decrease MMP-9, increase IL-10 and adiponectin acting as anti-atherogenic, anti-inflammatory and immunomodulatory in IR type 2 DM.
authors.affiliation: Department of Pharmacology, Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Mahal, Jagatpura, Jaipur 302025, Rajasthan, India. ashishksharma2003@yahoo.com
authors.forename: Ashish Kumar
authors.initials: AK
authors.lastname: Sharma
authors.forename: Sachin Kumar
authors.initials: SK
authors.lastname: Raikwar
authors.forename: Muneem Kumar
authors.initials: MK
authors.lastname: Kurmi
authors.forename: Bharthu Parthsarthi
authors.initials: BP
authors.lastname: Srinivasan
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D015248:Gemfibrozil / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D052242:Adiponectin; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D007328:Insulin; D016753:Interleukin-10; D008687:Metformin; D020780:Matrix Metalloproteinase 9; D015248:Gemfibrozil