Increase Fibroblast Activation Protein-α, but not Lowering of FGF Receptor and/or Co-Receptor, Causes Increase in Fibroblast Growth Factor-21 in T2D Independent on Diabetes Duration

Document Type : Original Article

Authors

1 MLT, College of Health and Medical Technologies; ATU. Kufa. Iraq

2 MTL, Kufa Institute, Al-Furat Al-Awsat Technical University, Najaf, Iraq

10.21608/asmj.2025.346942.1372

Abstract

Background: Diabetes mellitus is a major global public health issue. T2DM patients are associated with increased Fibroblast growth Factor 21 (FGF21). The reason of FGF-21 increase is controversial issue.
Aim of the Study: We aimed to investigate i) whether the increase in FGF21can explain by an increase in fibroblast activation protein-α (FAP-α) rather than inhibition in fibroblast growth factor receptor 1c (FGFR1 c) and/or β-Klotho (KLB). ii) The impact of DM duration on fibroblast growth factor 21 (FGF21), FGFR1c, KLB, and FAP-α. Subject and Methods: A total of forty participants were enrolled in this study. They were divided into: 20 healthy participants, and T2D groups which were included 9 participants (recently diagnosed as T2D) and 11 participants (were T2D with diabetes duration 1-6 years). Biochemical investigations (HbA1c, glucose level, lipid profile) and FGF21, FGFR1 c, KLB and FAP-α were measured in all participants.
Results: Our results showed that FGF-21 increased significantly by 2 folds in T2D (186.7±9.8 vs. 86±2.8, respectively), the level of FAP-α was also increased significantly in T2D group without effecting the KLB level, however, there was a slightly significant increase in FGFR1c. Moreover, prolong DM duration had no effect on the FGF21 and its receptor and co-receptor. Although, FAP-α was not affected by DM duration.
Conclusion: We conclude that FGF-21 resistance could be explained by deactivation of FGF-21 by FAP-α and the DM duration had no effect on FGF-21 and FAP-α or receptor and co-receptor.

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