Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway
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 (<i>n</i> = 12) were intraperitoneally admini...
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2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| author | Sarah M. AL-Qabbaa 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 Nouf M. Alrasheed |
| author_facet | Sarah M. AL-Qabbaa 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 Nouf M. Alrasheed |
| author_sort | Sarah M. AL-Qabbaa |
| collection | DOAJ |
| description | 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 (<i>n</i> = 12) were intraperitoneally administered a single dose of streptozotocin (30 mg/kg) to induce diabetes. Streptozotocin-treated and untreated rats (<i>n</i> = 12) were further divided into normal control, normal sitagliptin-treated control, diabetic control, and sitagliptin-treated diabetic groups (<i>n</i> = 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 (<i>p</i> < 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. |
| first_indexed | 2024-03-11T05:34:38Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:34:38Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2baa7472456a40dd970461f1f5a7a2d32023-11-17T16:52:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247653210.3390/ijms24076532Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT PathwaySarah M. AL-Qabbaa0Samaher I. Qaboli1Tahani K. Alshammari2Maha A. Alamin3Haya M. Alrajeh4Lama A. Almuthnabi5Rana R. Alotaibi6Asma S. Alonazi7Anfal F. Bin Dayel8Nawal M. Alrasheed9Nouf M. Alrasheed10PharmD. Program, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaPharmD. Program, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaPharmD. Program, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaPharmD. Program, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDiabetic 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 (<i>n</i> = 12) were intraperitoneally administered a single dose of streptozotocin (30 mg/kg) to induce diabetes. Streptozotocin-treated and untreated rats (<i>n</i> = 12) were further divided into normal control, normal sitagliptin-treated control, diabetic control, and sitagliptin-treated diabetic groups (<i>n</i> = 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 (<i>p</i> < 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.https://www.mdpi.com/1422-0067/24/7/6532diabetic nephropathyJanus kinase/signal transducer activator of transcription pathwayprotein tyrosine phosphatase 1Binflammation |
| spellingShingle | Sarah M. AL-Qabbaa 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 Nouf M. Alrasheed 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 diabetic nephropathy Janus kinase/signal transducer activator of transcription pathway protein tyrosine phosphatase 1B inflammation |
| title | Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway |
| title_full | Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway |
| title_fullStr | Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway |
| title_full_unstemmed | Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway |
| title_short | Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway |
| title_sort | sitagliptin mitigates diabetic nephropathy in a rat model of streptozotocin induced type 2 diabetes possible role of ptp1b jak stat pathway |
| topic | diabetic nephropathy Janus kinase/signal transducer activator of transcription pathway protein tyrosine phosphatase 1B inflammation |
| url | https://www.mdpi.com/1422-0067/24/7/6532 |
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