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The potential effect of metformin on fibroblast growth factor 21 in type 2 diabetes mellitus (T2DM)

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Abstract

Fibroblast growth factor 21 (FGF21) is a peptide hormone mainly synthesized and released from the liver. FGF21 acts on FGF21 receptors (FGFRs) and β-Klotho, which is a transmembrane co-receptor. In type 2 diabetes mellitus (T2DM), inflammatory disorders stimulate the release of FGF21 to overcome insulin resistance (IR). FGF21 improves insulin sensitivity and glucose homeostasis. Metformin which is used in the management of T2DM may increase FGF21 expression. Accordingly, the objective of this review was to clarify the metformin effect on FGF21 in T2DM. FGF21 level and expression of FGF2Rs are dysregulated in T2DM due to the development of FGF21 resistance. Metformin stimulates the hepatic expression of FGF21/FGF2Rs by different signaling pathways. Besides, metformin improves the expression of β-Klotho which improves FGF21 sensitivity. In conclusion, metformin advances FGF21 signaling and decreases FGF21 resistance in T2DM, and this might be an innovative mechanism for metformin in the enhancement of glucose homeostasis and metabolic disorders in T2DM patients.

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  1. Department of Pharmacology, Toxicology and Medicine, Medical Faculty, College of Medicine, Al-Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq

    Hayder M. Al-kuraishy & Ali I. Al-Gareeb

  2. Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, Marsa Matruh, 51744, Egypt

    Hebatallah M. Saad

  3. Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, Egypt

    Gaber El-Saber Batiha

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  1. Hayder M. Al-kuraishy
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  2. Ali I. Al-Gareeb
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  3. Hebatallah M. Saad
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  4. Gaber El-Saber Batiha
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HMAK and AIA conceptualized the manuscript, wrote, edited, and reviewed the main text and approved the final edition of the manuscript. HMS and GESB prepared the figures, wrote, corrected, amended, and approved the final edition of the manuscript.

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Correspondence to Hebatallah M. Saad or Gaber El-Saber Batiha.

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Al-kuraishy, H.M., Al-Gareeb, A.I., Saad, H.M. et al. The potential effect of metformin on fibroblast growth factor 21 in type 2 diabetes mellitus (T2DM). Inflammopharmacol 31, 1751–1760 (2023). https://doi.org/10.1007/s10787-023-01255-4

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