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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

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Abstract

Aim

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.

Essential methods

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.

Main 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).

Overall 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.

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Acknowledgments

Authors are thankful to AICTE, New Delhi, India; Panecea Biotec Ltd., New Delhi, India & Nicholas Piramal Limited. Mumbai, India for providing the gift samples of the drugs.

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It is stated that there are no conflict of interest.

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The experimental protocol was approved by Institutional Animal Ethical Committee (Protocol number: DIPSAR/IACE/14/2006).

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Authors and Affiliations

  1. Department of Pharmacology, Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Mahal, Jagatpura, Jaipur, 302025, Rajasthan, India

    Ashish Kumar Sharma, Sachin Kumar Raikwar & Muneem Kumar Kurmi

  2. Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research, New Delhi, 110017, India

    Bharthu Parthsarthi Srinivasan

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  1. Ashish Kumar Sharma
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Sharma, A.K., Raikwar, S.K., Kurmi, M.K. et al. 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. Inflammopharmacol 21, 137–145 (2013). https://doi.org/10.1007/s10787-012-0154-4

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