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Article

Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway

by
Sarah M. AL-Qabbaa
1,
Samaher I. Qaboli
1,
Tahani K. Alshammari
2,
Maha A. Alamin
2,
Haya M. Alrajeh
2,
Lama A. Almuthnabi
1,
Rana R. Alotaibi
1,
Asma S. Alonazi
2,
Anfal F. Bin Dayel
2,
Nawal M. Alrasheed
2 and
Nouf M. Alrasheed
2,*
1
PharmD. Program, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
2
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(7), 6532; https://doi.org/10.3390/ijms24076532
Submission received: 3 March 2023 / Revised: 27 March 2023 / Accepted: 29 March 2023 / Published: 31 March 2023
(This article belongs to the Special Issue Molecular Mechanisms of Diabetic Kidney Disease)
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Abstract

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus. This study examined the therapeutic effects of sitagliptin, a dipeptidyl peptidase inhibitor, on DN and explored the underlying mechanism. Male Wistar albino rats (n = 12) were intraperitoneally administered a single dose of streptozotocin (30 mg/kg) to induce diabetes. Streptozotocin-treated and untreated rats (n = 12) were further divided into normal control, normal sitagliptin-treated control, diabetic control, and sitagliptin-treated diabetic groups (n = 6 in each). The normal and diabetic control groups received normal saline, whereas the sitagliptin-treated control and diabetic groups received sitagliptin (100 mg/kg, p.o.). We assessed the serum levels of DN and inflammatory biomarkers. Protein tyrosine phosphatase 1 B (PTP1B), phosphorylated Janus kinase 2 (P-JAK2), and phosphorylated signal transducer activator of transcription (P-STAT3) levels in kidney tissues were assessed using Western blotting, and kidney sections were examined histologically. Sitagliptin reduced DN and inflammatory biomarkers and the expression of PTP1B, p-JAK2, and p-STAT3 (p < 0.001) and improved streptozotocin-induced histological changes in the kidney. These results demonstrate that sitagliptin ameliorates inflammation by inhibiting DPP-4 and consequently modulating the PTP1B-related JAK/STAT axis, leading to the alleviation of DN.
Keywords: diabetic nephropathy; Janus kinase/signal transducer activator of transcription pathway; protein tyrosine phosphatase 1B; inflammation diabetic nephropathy; Janus kinase/signal transducer activator of transcription pathway; protein tyrosine phosphatase 1B; inflammation
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MDPI and ACS Style

AL-Qabbaa, S.M.; Qaboli, S.I.; Alshammari, T.K.; Alamin, M.A.; Alrajeh, H.M.; Almuthnabi, L.A.; Alotaibi, R.R.; Alonazi, A.S.; Bin Dayel, A.F.; Alrasheed, N.M.; et al. Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway. Int. J. Mol. Sci. 2023, 24, 6532. https://doi.org/10.3390/ijms24076532

AMA Style

AL-Qabbaa SM, Qaboli SI, Alshammari TK, Alamin MA, Alrajeh HM, Almuthnabi LA, Alotaibi RR, Alonazi AS, Bin Dayel AF, Alrasheed NM, et al. Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway. International Journal of Molecular Sciences. 2023; 24(7):6532. https://doi.org/10.3390/ijms24076532

Chicago/Turabian Style

AL-Qabbaa, Sarah M., Samaher I. Qaboli, Tahani K. Alshammari, Maha A. Alamin, Haya M. Alrajeh, Lama A. Almuthnabi, Rana R. Alotaibi, Asma S. Alonazi, Anfal F. Bin Dayel, Nawal M. Alrasheed, and et al. 2023. "Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway" International Journal of Molecular Sciences 24, no. 7: 6532. https://doi.org/10.3390/ijms24076532

APA Style

AL-Qabbaa, S. M., Qaboli, S. I., Alshammari, T. K., Alamin, M. A., Alrajeh, H. M., Almuthnabi, L. A., Alotaibi, R. R., Alonazi, A. S., Bin Dayel, A. F., Alrasheed, N. M., & Alrasheed, N. M. (2023). Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway. International Journal of Molecular Sciences, 24(7), 6532. https://doi.org/10.3390/ijms24076532

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