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Could Increased Glp1r Expression via Sitagliptin in the GLP-1/GLP-1 Receptor Axis in the DietInduced Obesity Rat Model be Important in Liver Metabolism?

Year 2024, Volume: 14 Issue: 3, 210 - 214, 19.12.2024
https://doi.org/10.26650/experimed.1565962

Abstract

Objective: The aim of this study was to evaluate the contribution of sitagliptin, which is used in the treatment of type 2 diabetes mellitus due to its insulinotropic effects, to the levels of glucagon-like peptide-1 (GLP-1) expressed in many systemic tissues in obesity, in liver, skeletal muscle, and fat tissue.

Materials and Methods: Adult Wistar albino rats (n=32) were randomly divided into four groups for 16 weeks of intervention. These groups were control (C) (n=8), obese (Ob) (n=8), sitagliptin (C+Stg) (n=8), and obese (Ob+Stg) given sitagliptin (n=8). Glp1r expression in rat liver, muscle, and adipose tissue was confirmed by quantitative real-time PCR.

Results: No significant change was detected in Glp1r expression levels in muscle and fat tissue in 4 groups. A 10.64-fold increase in Glp1r gene expression was observed in Ob compared to C (p=0.008). Additionally, a 4.03-fold increase in expression level was found in Ob+Stg compared to Ob (p=0.02) and a 12.52-fold increase in expression level was found in Ob+Stg compared to C (p=0.01).

Conclusion: The increased Glp1r expression intensity in obese individuals using sitagliptin compared with controls and obese individuals not using sitagliptin may play a role in the reorganization of liver metabolism that is impaired due to obesity, such as the gluconeogenesis process.

References

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  • 7. Kosat E. Sitagliptin’in rat karaciğer ve böbrek dokusunda oksidatif stres metabolizmasi üzerine etkisi. Adnan Menderes Üniversitesi, Sağlık Bilimleri Enstitüsü, Yüksek Lisans Tezi. 2011. google scholar
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  • 13. Coskun ZM, Koyuturk M, Karabulut S, Bolkent S. CB-1R and GLP-1R gene expressions and oxidative stress in the liver of diabetic rats treated with sitagliptin. Pharmacol Rep 2017; 69(4): 822-9. google scholar
  • 14. O’Harte FP, Gray AM, Abdel-Wahab YH, Flatt PR. Effects of non-glycated and glycated glucagon-like peptide-1(7-36) amide on glucose metabolism in isolated mouse abdominal muscle. Peptides 1997; 18(9): 1327-33. google scholar
  • 15. Kato H, Nagai Y, Ohta A, Tenjin A, Nakamura Y, Tsukiyama H, et al. Effect of sitagliptin on intrahepatic lipid content and body fat in patients with type 2 diabetes. Diabetes Res Clin Pract 2015; 109(1): 199-205. google scholar
  • 16. Prakash S, Rai U, Kosuru R, Tiwari V, Singh S. Amelioration of diet-induced metabolic syndrome and fatty liver with sitagliptin via regulation of adipose tissue inflammation and hepatic Adiponectin/AMPK levels in mice. Biochimie 2020; 168: 198-209. google scholar
  • 17. Nahon KJ, Doornink F, Straat ME, Botani K, Martinez-Tellez B, Abreu-Vieira G, et al. Effect of sitagliptin on energy metabolism and brown adipose tissue in overweight individuals with prediabetes: a randomised placebo-controlled trial. Diabetologia. 2018; 61(11): 2386-97. google scholar
  • 18. Akaslan SB, Degertekin CK, Yilmaz G, Cakir N, Arslan M, Toruner FB. Effects of sitagliptin on nonalcoholic fatty liver disease in diet-induced obese rats. Metab Syndr Relat Disord 2013; 11(4): 243-50. google scholar
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  • 21. Tremblay AJ, Lamarche B, Kelly I, Charest A, Lepine MC, Droit A, et al. Effect of sitagliptin therapy on triglyceride-rich lipoprotein kinetics in patients with type 2 diabetes. Diabetes Obes Metab 2014; 16(12): 1223-9. google scholar
  • 22. Hematyar J, Rashidi H, Zakerkish M, Payami SP, Ghaderian SB. Effect of sitagliptin versus glibenclamide on glycemic markers, lipid profile inflammatory and oxidative stress factors in type 2 diabetes patients: a double-blinded randomized controlled trial. Maedica (Bucur) 2022; 17(4): 762-70. google scholar
  • 23. Li S, Li H, Wang R, Zhang JP. The effect of sitagliptin on obese patients with insulin treatment-induced diabetes mellitus. Eur Rev Med Pharmacol Sci 2017; 21(15): 3490-5. google scholar
  • 24. Shams HA, Aziz HM, Al-Kuraishy HM. The potential effects of metformin and/or sitagliptin on leptin/adiponectin ratio in diabetic obese patients: a new therapeutic effect. J Pak Med Assoc 2024; 74(10 (Supple-8)): 241-5. google scholar
  • 25. Wang X, Weng W, Cui Y, Zou C. Sitagliptin alleviates obesity in immature mice by inhibiting oxidative stress and inflammation. Reprod Sci 2024; 31(11): 3549-59. google scholar
  • 26. Zong Y, Wang X, Zhang Y, Tan N, Zhang Y, Li L, Liu L. Sitagliptin ameliorates Creb5/lncRNA ENSMUST00000213271-mediated vascular endothelial dysfunction in obese mice. Cardiovasc Drugs Ther 2024; 38(4): 679-91. google scholar
Year 2024, Volume: 14 Issue: 3, 210 - 214, 19.12.2024
https://doi.org/10.26650/experimed.1565962

Abstract

References

  • 1. Burcelin R, Gourdy P. Harnessing glucagon-like peptide-1 receptor agonists for the pharmacological treatment of overweight and obesity. Obes Rev 2017; 18(1): 86-98. google scholar
  • 2. Scott LJ. Sitagliptin: A review in type 2 diabetes. Drugs 2017; 77(2): 209-24. google scholar
  • 3. Sheikh A. Direct cardiovascular effects of glucagon like peptide-1. Diabetol Metab Syndr 2013; 5(1): 47. google scholar
  • 4. Nauck MA, Heimesaat MM, Behle K, Holst JJ, Nauck MS, Ritzel R, et al. Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab 2002; 87: 1239-46. google scholar
  • 5. McIntosh CH, Demuth HU, Pospisilik JA, Pederson R. Dipeptidyl peptidase IV inhibitors: how do they work as new antidiabetic agents? Regul Pept 2005; 128(2): 159-65. google scholar
  • 6. Mannucci E, Pala L, Ciani S, Bardini G, Pezzatini A, Sposato I, et al. Hyperglycaemia increases dipeptidyl peptidase IV activity in diabetes mellitus. Diabetologia 2005; 48(6): 1168-72. google scholar
  • 7. Kosat E. Sitagliptin’in rat karaciğer ve böbrek dokusunda oksidatif stres metabolizmasi üzerine etkisi. Adnan Menderes Üniversitesi, Sağlık Bilimleri Enstitüsü, Yüksek Lisans Tezi. 2011. google scholar
  • 8. Dupre J, Behme MT, Hramiak IM, McFarlane P, Williamson MP, Zabel P, et al. Glucagon-like peptide I reduces postprandial glycemic excursions in IDDM. Diabetes. 1995; 44(6): 626-30. google scholar
  • 9. Ahren B. DPP-4 inhibitors. Best Pract Res Clin Endocrinol Metab 2007; 21(4): 517-33. google scholar
  • 10. Roberge JN, Brubaker PL. Secretion of proglucagon-derived peptides in response to intestinal luminal nutrients. Endocrinology 1991; 128(6): 3169-74. google scholar
  • 11. Hewedy WA. Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice. Brazilian J Pharma Sci 2020; 56: e18482. google scholar
  • 12. Karasik A, Aschner P, Katzeff H, Davies MJ, Stein PP. Sitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials. Curr Med Res Opin 2008; 24(2): 489-96. google scholar
  • 13. Coskun ZM, Koyuturk M, Karabulut S, Bolkent S. CB-1R and GLP-1R gene expressions and oxidative stress in the liver of diabetic rats treated with sitagliptin. Pharmacol Rep 2017; 69(4): 822-9. google scholar
  • 14. O’Harte FP, Gray AM, Abdel-Wahab YH, Flatt PR. Effects of non-glycated and glycated glucagon-like peptide-1(7-36) amide on glucose metabolism in isolated mouse abdominal muscle. Peptides 1997; 18(9): 1327-33. google scholar
  • 15. Kato H, Nagai Y, Ohta A, Tenjin A, Nakamura Y, Tsukiyama H, et al. Effect of sitagliptin on intrahepatic lipid content and body fat in patients with type 2 diabetes. Diabetes Res Clin Pract 2015; 109(1): 199-205. google scholar
  • 16. Prakash S, Rai U, Kosuru R, Tiwari V, Singh S. Amelioration of diet-induced metabolic syndrome and fatty liver with sitagliptin via regulation of adipose tissue inflammation and hepatic Adiponectin/AMPK levels in mice. Biochimie 2020; 168: 198-209. google scholar
  • 17. Nahon KJ, Doornink F, Straat ME, Botani K, Martinez-Tellez B, Abreu-Vieira G, et al. Effect of sitagliptin on energy metabolism and brown adipose tissue in overweight individuals with prediabetes: a randomised placebo-controlled trial. Diabetologia. 2018; 61(11): 2386-97. google scholar
  • 18. Akaslan SB, Degertekin CK, Yilmaz G, Cakir N, Arslan M, Toruner FB. Effects of sitagliptin on nonalcoholic fatty liver disease in diet-induced obese rats. Metab Syndr Relat Disord 2013; 11(4): 243-50. google scholar
  • 19. Tahara A, Matsuyama-Yokono A, Shibasaki M. Effects of antidiabetic drugs in high-fat diet and streptozotocin-nicotinamide-induced type 2 diabetic mice. Eur J Pharmacol 2011; 655(1-3): 108-16. google scholar
  • 20. Yang F, Dang S, Lv H, Shi B. Combined treatment with a gastric inhibitory polypeptide receptor antagonist and a peptidyl peptidase-4 inhibitor improves metabolic abnormalities in diabetic mice. J Int Med Res 2021; 49(1): 300060520985664. google scholar
  • 21. Tremblay AJ, Lamarche B, Kelly I, Charest A, Lepine MC, Droit A, et al. Effect of sitagliptin therapy on triglyceride-rich lipoprotein kinetics in patients with type 2 diabetes. Diabetes Obes Metab 2014; 16(12): 1223-9. google scholar
  • 22. Hematyar J, Rashidi H, Zakerkish M, Payami SP, Ghaderian SB. Effect of sitagliptin versus glibenclamide on glycemic markers, lipid profile inflammatory and oxidative stress factors in type 2 diabetes patients: a double-blinded randomized controlled trial. Maedica (Bucur) 2022; 17(4): 762-70. google scholar
  • 23. Li S, Li H, Wang R, Zhang JP. The effect of sitagliptin on obese patients with insulin treatment-induced diabetes mellitus. Eur Rev Med Pharmacol Sci 2017; 21(15): 3490-5. google scholar
  • 24. Shams HA, Aziz HM, Al-Kuraishy HM. The potential effects of metformin and/or sitagliptin on leptin/adiponectin ratio in diabetic obese patients: a new therapeutic effect. J Pak Med Assoc 2024; 74(10 (Supple-8)): 241-5. google scholar
  • 25. Wang X, Weng W, Cui Y, Zou C. Sitagliptin alleviates obesity in immature mice by inhibiting oxidative stress and inflammation. Reprod Sci 2024; 31(11): 3549-59. google scholar
  • 26. Zong Y, Wang X, Zhang Y, Tan N, Zhang Y, Li L, Liu L. Sitagliptin ameliorates Creb5/lncRNA ENSMUST00000213271-mediated vascular endothelial dysfunction in obese mice. Cardiovasc Drugs Ther 2024; 38(4): 679-91. google scholar
There are 26 citations in total.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other)
Journal Section Research Article
Authors

Neslihan Cevik 0000-0001-9631-8221

Gülper Nacarkahya 0000-0002-8512-8833

Serkan Gürgül 0000-0002-1450-490X

Cem Horozoğlu 0000-0001-8998-2028

Publication Date December 19, 2024
Submission Date October 13, 2024
Acceptance Date December 2, 2024
Published in Issue Year 2024 Volume: 14 Issue: 3

Cite

Vancouver Cevik N, Nacarkahya G, Gürgül S, Horozoğlu C. Could Increased Glp1r Expression via Sitagliptin in the GLP-1/GLP-1 Receptor Axis in the DietInduced Obesity Rat Model be Important in Liver Metabolism?. Experimed. 2024;14(3):210-4.