The effects of metformin monotherapy and combination of metformin and glibenclamide therapy on the expression of RAGE, Sirt1, and Nrf2 genes in peripheral blood mononuclear cells of type 2 diabetic patients

Hashem Hosseinipoor; Seyed Yousef Kariminejad; Moharram Salehi; Mozhdeh Heidari; Mohammad Taghi Goodarzi; Mohammad Hossein Karimi

doi:10.1007/s40200-022-00984-7

The effects of metformin monotherapy and combination of metformin and glibenclamide therapy on the expression of RAGE, Sirt1, and Nrf2 genes in peripheral blood mononuclear cells of type 2 diabetic patients

J Diabetes Metab Disord. 2022 Feb 10;21(1):369-377. doi: 10.1007/s40200-022-00984-7. eCollection 2022 Jun.

Authors

Hashem Hosseinipoor¹, Seyed Yousef Kariminejad¹, Moharram Salehi¹, Mozhdeh Heidari², Mohammad Taghi Goodarzi¹, Mohammad Hossein Karimi²

Affiliations

¹ Department of Biochemistry, Shahrood Branch, Islamic Azad University, Shahrood, Iran.
² Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Abstract

Purpose: Although metformin is the first-line treatment of type 2 diabetes mellitus (T2DM), a few studies have evaluated the benefits of monotherapies (metformin) versus combination therapy (metformin and glibenclamide) for treatment of T2DM patients. The present study aimed to evaluate the effect of monotherapy with metformin compared to combination therapy with metformin and glibenclamide on the expression of RAGE, Nrf 2, and Sirt1genes.

Methods: EightyT2DM patients and 40 healthy individuals participated in this case-control study. The patients in the treatment group were divided into two groups who received either metformin alone (n = 40) or metformin in combination with glibenclamide (n = 40). FBS, HbA1c, and fructosamine were measured. The expression of RAGE, Nrf 2, and Sirt 1 genes in PBMC of all subjects were assessed using real-time PCR.

Results: RAGE gene expression in both treatment groups was significantly lower than the control (P < 0.05). RAGE gene expression was significantly reduced in the combination of metformin and glibenclamide treated group compared to metformin group (P < 0.05). Additionally, the expression of Sirt 1 and Nrf 2 genes in both treatment groups was higher than that of the control group (P < 0.05). The expression of Sirt 1 and Nrf 2 genes in metformin and glibenclamide treated group were higher than the metformin group (P < 0.05).

Conclusion: Combination therapy (metformin and glibenclamide) showed stronger effect on repression of the RAGE gene and activation of Nrf 2 and Sirt 1 genes compared to monotherapy (metformin); therefore, it can be concluded that combination therapy may have more protective effects on the T2DM patients. No significant correlation was observed between HbA1c and RAGE, Sirt 1, and Nrf 2 genes expression.

Keywords: Hyperglycemia. Diabetes. Metformin. Glibenclamide. Receptor for advanced glycation end products.