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Renoprotective Effect of Gemigliptin, a Dipeptidyl Peptidase-4 Inhibitor, in Streptozotocin-Induced Type 1 Diabetic Mice
Gwon-Soo Jung, Jae-Han Jeon, Mi Sun Choe, Sung-Woo Kim, In-Kyu Lee, Mi-Kyung Kim, Keun-Gyu Park
Diabetes Metab J. 2016;40(3):211-221.   Published online March 31, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.3.211
  • 7,154 View
  • 57 Download
  • 25 Web of Science
  • 25 Crossref
AbstractAbstract PDFPubReader   
Background

Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the treatment of patients with type 2 diabetes and have proven protective effects on diabetic kidney disease (DKD). Whether DPP-4 inhibitors have renoprotective effects on insulin-deficient type 1 diabetes has not been comprehensively examined. The aim of this study was to determine whether gemigliptin, a new DPP-4 inhibitor, has renoprotective effects in streptozotocin (STZ)-induced type 1 diabetic mice.

Methods

Diabetes was induced by intraperitoneal administration of a single dose of STZ. Mice with diabetes were treated without or with gemigliptin (300 mg/kg) for 8 weeks. Morphological changes of the glomerular basement membrane (GBM) were observed by electron microscopy and periodic-acid Schiff staining. In addition, we measured blood glucose and urinary albumin excretion and evaluated fibrotic markers using immunohistochemical staining, quantitative reverse transcription polymerase chain reaction analysis, and Western blot analysis.

Results

Gemigliptin did not reduce the blood glucose levels of STZ-treated mice. In gemigliptin-treated mice with STZ, a significant reduction in urinary albumin excretion and GBM thickness was observed. Immunohistological examination revealed that gemigliptin attenuated renal fibrosis induced by STZ and decreased extracellular matrix protein levels, including those of type I collagen and fibronectin, and Smad3 phosphorylation. In cultured rat renal cells, gemigliptin inhibited transforming growth factor β-stimulated type I collagen and fibronectin mRNA and protein levels via down-regulation of Smad3 phosphorylation.

Conclusion

Our data demonstrate that gemigliptin has renoprotective effects on DKD, regardless of its glucose-lowering effect, suggesting that it could be used to prevent DKD, including in patients with type 1 diabetes.

Citations

Citations to this article as recorded by  
  • Exendin-4, a glucagon-like peptide-1 receptor agonist, alleviates muscular dysfunction and wasting in a streptozotocin-induced diabetic mouse model compared to metformin
    Ding-Cheng Chan, Yuan-Cheng Lin, Huei-Ping Tzeng, Rong-Sen Yang, Meng-Tsan Chiang, Shing-Hwa Liu
    Tissue and Cell.2024; 89: 102479.     CrossRef
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    Jun-Kyu Byun, Gwon-Soo Jung
    Biochemical and Biophysical Research Communications.2024; 733: 150425.     CrossRef
  • Safety and Efficiency of Dipeptidyl Peptidase IV Inhibitors in Patients with Diabetic Kidney Disease: A Systematic Review and Meta-Analysis
    Adili Tuersun, Munire Mohetaer, Guanxin Hou, Gang Cheng
    Current Therapeutic Research.2024; 101: 100763.     CrossRef
  • Diabetic fibrosis
    Izabela Tuleta, Nikolaos G. Frangogiannis
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2021; 1867(4): 166044.     CrossRef
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    Heba El-Sayed Mostafa, Eman Ahmed Alaa El-Din, Dalia Abdallah El-Shafei, Nehal S. Abouhashem, Aisha Abdallah Abouhashem
    Environmental Science and Pollution Research.2021; 28(24): 31174.     CrossRef
  • Evogliptin, a Dipeptidyl Peptidase-4 Inhibitor, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
    Mi-Jin Kim, Na-young Kim, Yun-A Jung, Seunghyeong Lee, Gwon-Soo Jung, Jung-Guk Kim, In-Kyu Lee, Sungwoo Lee, Yeon-Kyung Choi, Keun-Gyu Park
    Diabetes & Metabolism Journal.2020; 44(1): 186.     CrossRef
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    Jung Beom Seo, Yeon-Kyung Choi, Hye-In Woo, Yun-A Jung, Sungwoo Lee, Seunghyeong Lee, Mihyang Park, In-Kyu Lee, Gwon-Soo Jung, Keun-Gyu Park
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    Clinical Cardiology.2018; 41(9): 1259.     CrossRef
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  • Dipeptidyl peptidase-4 inhibition and renoprotection
    Yuta Takagaki, Daisuke Koya, Keizo Kanasaki
    Current Opinion in Nephrology and Hypertension.2017; 26(1): 56.     CrossRef
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    Mi-Kyung Kim
    The Korean Journal of Internal Medicine.2017; 32(4): 622.     CrossRef
  • Pharmacological Treatment in Diabetes Mellitus Type 1 – Insulin and What Else?
    Ewa Otto-Buczkowska, Natalia Jainta
    International Journal of Endocrinology and Metabolism.2017;[Epub]     CrossRef
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  • Efficacy, safety and albuminuria‐reducing effect of gemigliptin in Korean type 2 diabetes patients with moderate to severe renal impairment: A 12‐week, double‐blind randomized study (the GUARD Study)
    Sun A. Yoon, Byoung G. Han, Sung G. Kim, Sang Y. Han, Young I. Jo, Kyung H. Jeong, Kook H. Oh, Hyeong C. Park, Sun H. Park, Shin W. Kang, Ki R. Na, Sun W. Kang, Nam H. Kim, Young H. Jang, Seong H. Shin, Dae R. Cha
    Diabetes, Obesity and Metabolism.2017; 19(4): 590.     CrossRef
  • Sodium butyrate has context-dependent actions on dipeptidyl peptidase-4 and other metabolic parameters
    Eun-Sol Lee, Dong-Sung Lee, Prakash Raj Pandeya, Youn-Chul Kim, Dae-Gil Kang, Ho-Sub Lee, Byung-Chul Oh, Dae Ho Lee
    The Korean Journal of Physiology & Pharmacology.2017; 21(5): 519.     CrossRef
  • Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
    Kwi-Hyun Bae, Jung Beom Seo, Yun-A Jung, Hye-Young Seo, Sun Hee Kang, Hui-Jeon Jeon, Jae Man Lee, Sungwoo Lee, Jung-Guk Kim, In-Kyu Lee, Gwon-Soo Jung, Keun-Gyu Park
    Endocrinology and Metabolism.2017; 32(1): 115.     CrossRef
  • Gemigliptin: An Update of Its Clinical Use in the Management of Type 2 Diabetes Mellitus
    Sung-Ho Kim, Jung-Hwa Yoo, Woo Je Lee, Cheol-Young Park
    Diabetes & Metabolism Journal.2016; 40(5): 339.     CrossRef
  • Risk assessment and management of post-transplant diabetes mellitus
    Eugene Han, Myoung Soo Kim, Yu Seun Kim, Eun Seok Kang
    Metabolism.2016; 65(10): 1559.     CrossRef
The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes
Eun Yeong Choe, Yongin Cho, Younjeong Choi, Yujung Yun, Hye Jin Wang, Obin Kwon, Byung-Wan Lee, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee, Eun Seok Kang
Diabetes Metab J. 2014;38(3):211-219.   Published online June 17, 2014
DOI: https://doi.org/10.4093/dmj.2014.38.3.211
  • 5,538 View
  • 77 Download
  • 27 Web of Science
  • 25 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We evaluated the effects of two dipeptidyl peptidase-4 (DPP-4) inhibitors, sitagliptin and vildagliptin, on metabolic parameters in patients with type 2 diabetes mellitus.

Methods

A total of 170 type 2 diabetes patients treated with sitagliptin or vildagliptin for more than 24 weeks were selected. The patients were separated into two groups, sitagliptin (100 mg once daily, n=93) and vildagliptin (50 mg twice daily, n=77). We compared the effect of each DPP-4 inhibitor on metabolic parameters, including the fasting plasma glucose (FPG), postprandial glucose (PPG), glycated hemoglobin (HbA1c), and glycated albumin (GA) levels, and lipid parameters at baseline and after 24 weeks of treatment.

Results

The HbA1c, FPG, and GA levels were similar between the two groups at baseline, but the sitagliptin group displayed a higher PPG level (P=0.03). After 24 weeks of treatment, all of the glucose-related parameters were significantly decreased in both groups (P=0.001). The levels of total cholesterol and triglycerides were only reduced in the vildagliptin group (P=0.001), although the sitagliptin group received a larger quantity of statins than the vildagliptin group (P=0.002).The mean change in the glucose- and lipid-related parameters after 24 weeks of treatment were not significantly different between the two groups (P=not significant). Neither sitagliptin nor vildagliptin treatment was associated with a reduction in the high sensitive C-reactive protein level (P=0.714).

Conclusion

Vildagliptin and sitagliptin exert a similar effect on metabolic parameters, but vildagliptin exerts a more potent beneficial effect on lipid parameters.

Citations

Citations to this article as recorded by  
  • Insulin Tregopil: An Ultra-Fast Oral Recombinant Human Insulin Analog: Preclinical and Clinical Development in Diabetes Mellitus
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    Eugene Han, Minyoung Lee, Yong-ho Lee, Hye Soon Kim, Byung-wan Lee, Bong-Soo Cha, Eun Seok Kang
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  • Response: The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes (Diabetes Metab J2014;38:211-9)
    EunYeong Choe, Eun Seok Kang
    Diabetes & Metabolism Journal.2014; 38(4): 319.     CrossRef
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    Seung-Hwan Lee
    Diabetes & Metabolism Journal.2014; 38(4): 317.     CrossRef

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