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Published in: Journal of Diabetes & Metabolic Disorders 1/2021

01-06-2021 | Sitagliptin | Research article

Impact of combined therapy of mesenchymal stem cells and sitagliptin on a metabolic syndrome rat model

Authors: Yossra Ahmed, Zeinab Y. Ali, Mona A. Mohamed, Laila A. Rashed, Ehsan K. Mohamed

Published in: Journal of Diabetes & Metabolic Disorders | Issue 1/2021

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Abstract

Background

Emerging evidence suggests that mesenchymal stem cells (MSCs) have many anti-inflammatory and regenerative properties, which makes it a suitable candidate for the treatment of many diseases including metabolic syndrome (MetS). However, a major difficulty with stem cell therapy is to maintain cell viability, properties and function after implantation in vivo. This study aims to test the hypothesis that the combined therapy of MSCs and sitagliptin can effectively ameliorate MetS complications induced by high-fat and high-fructose diet (HFFD) in rats.

Methods

Rats were fed either standard diet (Control group) or HFFD. After 3 months, a group of HFFD animals was injected by a single dose of MSCs, another group received a daily oral dose of 10 mg/kg b.w. of sitagliptin, and the third group received the combined therapy of MSCs + sitagliptin for 1 month.

Results

Both MSCs and sitagliptin restored insulin sensitivity and reduced the HOMA-IR value in HFFD rats. The hepatic IRS-1 and Akt at both gene and protein levels, as well as the hepatic protein levels of IR and GLUT4 were improved. Downregulation of CHOP and NF-κB and upregulation of hepatic HO-1 expression and activity were also reported. Although MSCs and sitagliptin as monotherapy lead to remarkable effects, the dual application revealed the best results. Interestingly, histological findings confirmed these protective effects of the combined therapy against MetS complications.

Conclusion

Combined therapy of MSCs and sitagliptin can efficiently ameliorate the insulin resistance and promote the regeneration of hepatocytes in the metabolic syndrome rat model.
Literature
9.
go back to reference Jaiswal N, Haynesworth S, Caplan A, Bruder S. Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem. 1997;64:295–312 PMID:9027589.CrossRef Jaiswal N, Haynesworth S, Caplan A, Bruder S. Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem. 1997;64:295–312 PMID:9027589.CrossRef
13.
go back to reference Gornal AG, Bardawil CJ, David MM. Determination of serum proteins by means of biuret reaction. J Biol Chem. 1949;177:751–66 PMID:18110453.CrossRef Gornal AG, Bardawil CJ, David MM. Determination of serum proteins by means of biuret reaction. J Biol Chem. 1949;177:751–66 PMID:18110453.CrossRef
18.
23.
go back to reference Ammar HI, Sequiera GL, Nashed MB, Ammar RI, Gabr HM, Elsayed HE, et al. Comparison of adipose tissue- and bone marrow- derived mesenchymal stem cells for alleviating doxorubicin-induced cardiac dysfunction in diabetic rats. Stem Cell Res Ther. 2015;6:148. https://doi.org/10.1186/s13287-015-0142-x. Ammar HI, Sequiera GL, Nashed MB, Ammar RI, Gabr HM, Elsayed HE, et al. Comparison of adipose tissue- and bone marrow- derived mesenchymal stem cells for alleviating doxorubicin-induced cardiac dysfunction in diabetic rats. Stem Cell Res Ther. 2015;6:148. https://​doi.​org/​10.​1186/​s13287-015-0142-x.
25.
go back to reference Zhou Y, Hu Q, Chen F, Zhang J, Guo J, Wang H, et al. Human umbilical cord matrix-derived stem cells exert trophic effects on beta cell survival in diabetic rats and isolated islets. Dis Model Mech. 2015;8:1625–33. https://doi.org/10.1242/dmm.021857. Zhou Y, Hu Q, Chen F, Zhang J, Guo J, Wang H, et al. Human umbilical cord matrix-derived stem cells exert trophic effects on beta cell survival in diabetic rats and isolated islets. Dis Model Mech. 2015;8:1625–33. https://​doi.​org/​10.​1242/​dmm.​021857.
26.
go back to reference Xie Z, Hao H, Tong C, Cheng Y, Liu J, Pang Y, et al. Human umbilical cord-derived mesenchymal stem cells elicit macrophages into an anti-inflammatory phenotype to alleviate insulin resistance in type 2 diabetic rats. Stem Cells. 2016;34:627–39. https://doi.org/10.1002/stem.2238. Xie Z, Hao H, Tong C, Cheng Y, Liu J, Pang Y, et al. Human umbilical cord-derived mesenchymal stem cells elicit macrophages into an anti-inflammatory phenotype to alleviate insulin resistance in type 2 diabetic rats. Stem Cells. 2016;34:627–39. https://​doi.​org/​10.​1002/​stem.​2238.
36.
go back to reference Lee MR, Bae SJ, Kim JE, Song BR, Choi JY, Park JJ, et al. Inhibition of endoplasmic reticulum stress in high-fat-diet-induced obese C57BL/6 mice: efficacy of a novel extract from mulberry (Morus alba) leaves fermented with Cordyceps militaris. Lab Anim Res. 2018;34:288–94. https://doi.org/10.5625/lar.2018.34.4.288. Lee MR, Bae SJ, Kim JE, Song BR, Choi JY, Park JJ, et al. Inhibition of endoplasmic reticulum stress in high-fat-diet-induced obese C57BL/6 mice: efficacy of a novel extract from mulberry (Morus alba) leaves fermented with Cordyceps militaris. Lab Anim Res. 2018;34:288–94. https://​doi.​org/​10.​5625/​lar.​2018.​34.​4.​288.
38.
go back to reference Zhu W, Niu X, Wang M, Li Z, Jiang HK, Li C, et al. Endoplasmic reticulum stress may be involved in insulin resistance and lipid metabolism disorders of the white adipose tissues induced by high-fat diet containing industrial trans-fatty acids. Diabetes Metab Syndr Obes. 2019;12:1625–38. https://doi.org/10.2147/DMSO.S218336. Zhu W, Niu X, Wang M, Li Z, Jiang HK, Li C, et al. Endoplasmic reticulum stress may be involved in insulin resistance and lipid metabolism disorders of the white adipose tissues induced by high-fat diet containing industrial trans-fatty acids. Diabetes Metab Syndr Obes. 2019;12:1625–38. https://​doi.​org/​10.​2147/​DMSO.​S218336.
43.
go back to reference Feinstein R, Kanety H, Papa MZ, Lunenfeld B, Karasik A. Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. J Biol Chem. 1993;268:26055–8 PMID: 8253716.CrossRef Feinstein R, Kanety H, Papa MZ, Lunenfeld B, Karasik A. Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. J Biol Chem. 1993;268:26055–8 PMID: 8253716.CrossRef
Metadata
Title
Impact of combined therapy of mesenchymal stem cells and sitagliptin on a metabolic syndrome rat model
Authors
Yossra Ahmed
Zeinab Y. Ali
Mona A. Mohamed
Laila A. Rashed
Ehsan K. Mohamed
Publication date
01-06-2021
Publisher
Springer International Publishing
Published in
Journal of Diabetes & Metabolic Disorders / Issue 1/2021
Electronic ISSN: 2251-6581
DOI
https://doi.org/10.1007/s40200-021-00778-3

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