Serum dipeptidyl peptidase 4 activity in children with type 1 diabetes mellitus (original) (raw)

Abstract

Background: It is poorly understood whether dipeptidyl peptidase 4 (DPP4) activity is altered and how DPP4 contributes to glycemic control in patients with type 1 diabetes mellitus (T1DM).

Aim: The aim of this study was to measure serum DPP4 activity and to assess its relationships to metabolic variables in T1DM children.

Methods: Serum DPP4 activity was determined using a fluorometric assay in 43 T1DM and 26 control children.

Results: Serum DPP4 activity was significantly higher in T1DM children than in controls (3.57±0.99 vs. 2.67±0.77 U/mL, p<0.001). In the T1DM children, DPP4 activity was not correlated with HbA1c, blood glucose, or diabetes duration. A significant negative correlation was found between DPP4 activity and serum adiponectin levels in the T1DM group (r=–0.35, p<0.05).

Conclusions: Serum DPP4 activity was increased in the T1DM children, whereas it was not associated with glycemic control. Given the negative correlation between serum DPP4 and adiponectin levels, further investigations are warranted to elucidate the role of DPP4 on insulin sensitivity in T1DM children.

This work was supported by JSPS KAKENHI Grant Number 24591501.

Conflict of interests statement: The authors declare that they have no conflict of interest.

References

1. Gorrell MD, Gysbers V, McCaughan GW. CD26: a multifunctional integral membrane and secreted protein of activated lymphocytes. Scand J Immunol 2001;54:249–64.10.1046/j.1365-3083.2001.00984.x Search in Google Scholar

2. Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, et al. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 2006;29:2632–7.10.2337/dc06-0703 Search in Google Scholar

3. Chia CW, Egan JM. Incretin-based therapies in type 2 diabetes mellitus. J Clin Endocrinol Metab 2008;93:3703–16.10.1210/jc.2007-2109 Search in Google Scholar

4. Ellis SL, Moser EG, Snell-Bergeon JK, Rodionova AS, Hazenfield RM, et al. Effect of sitagliptin on glucose control in adult patients with type 1 diabetes: a pilot, double-blind, randomized, crossover trial. Diabet Med 2011;28:1176–81.10.1111/j.1464-5491.2011.03331.x Search in Google Scholar

5. Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 2001;358:221–9.10.1016/S0140-6736(01)05415-0 Search in Google Scholar

6. Schloot NC, Hanifi-Moghaddam P, Aabenhus-Andersen N, Alizadeh BZ, Saha MT, et al. Association of immune mediators at diagnosis of type 1 diabetes with later clinical remission. Diabet Med 2007;24:512–20.10.1111/j.1464-5491.2007.02096.x Search in Google Scholar PubMed

7. Imagawa A, Hanafusa T, Itoh N, Waguri M, Yamamoto K, et al. Immunological abnormalities in islets at diagnosis paralleled further deterioration of glycaemic control in patients with recent-onset type I (insulin-dependent) diabetes mellitus. Diabetologia 1999;42:574–8.10.1007/s001250051197 Search in Google Scholar PubMed

8. Fleischer B. A novel pathway of human T cell activation via a 103 kD T cell activation antigen. J Immunol 1987;138:1346–50.10.4049/jimmunol.138.5.1346 Search in Google Scholar

9. Heike M, Mobius U, Knuth A, Meuer S, Meyer zum Buschenfelde KH. Tissue distribution of the T cell activation antigen Ta1. Serological, immunohistochemical and biochemical investigations. Clin Exp Immunol 1988;74:431–4.Search in Google Scholar

10. Morimoto C, Schlossman SF. The structure and function of CD26 in the T-cell immune response. Immunol Rev 1998;161:55–7.10.1111/j.1600-065X.1998.tb01571.x Search in Google Scholar PubMed

11. Lamers D, Famulla S, Wronkowitz N, Hartwig S, Lehr S, et al. Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes 2011; 60:1917–25.10.2337/db10-1707 Search in Google Scholar PubMed PubMed Central

12. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, et al. Paradoxical decrease of an adipose specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999:257;79–83.10.1006/bbrc.1999.0255 Search in Google Scholar PubMed

13. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941–6.10.1038/90984 Search in Google Scholar PubMed

14. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001;86:1930–5.10.1210/jcem.86.5.7463 Search in Google Scholar PubMed

15. Tschritter O, Fritsche A, Thamer C, Haap M, Shirkavand F, et al. Plasma adiponectin concentrations predict insulin sensitivity of both glucose and lipid metabolism. Diabetes 2003;52: 239–43.10.2337/diabetes.52.2.239 Search in Google Scholar PubMed

16. Pereira RI, Snell-Bergeon JK, Erickson C, Schauer IE, Bergman BC, et al. Adiponectin dysregulation and insulin resistance in type 1 diabetes. J Clin Endocrinol Metab 2012;97:E642–7.10.1210/jc.2011-2542 Search in Google Scholar PubMed PubMed Central

17. Matheeussen V, Lambeir AM, Jungraithmayr W, Gomez N, Mc Entee K, et al. Method comparison of dipeptidyl peptidase IV activity assays and their application in biological samples containing reversible inhibitors. Clin Chim Acta 2012;413: 456–62.10.1016/j.cca.2011.10.031 Search in Google Scholar PubMed

18. Mannucci E, Pala L, Ciani S, Bardini G, Pezzatini A, et al. Hyperglycaemia increases dipeptidyl peptidase IV activity in diabetes mellitus. Diabetologia 2005;48:1168–72.10.1007/s00125-005-1749-8 Search in Google Scholar PubMed

19. Varga T, Somogyi A, Barna G, Wichmann B, Nagy G, et al. Higher serum DPP-4 enzyme activity and decreased lymphocyte CD26 expression in type 1 diabetes. Pathol Oncol Res 2011;17: 925–30.10.1007/s12253-011-9404-9 Search in Google Scholar PubMed

20. Imagawa A, Funahashi T, Nakamura T, Moriwaki M, Tanaka S, et al. Elevated serum concentration of adipose-derived factor, adiponectin, in patients with type 1 diabetes. Diabetes Care 2002;25:1665–6.10.2337/diacare.25.9.1665 Search in Google Scholar PubMed

21. Celi F, Bini V, Papi F, Santilli E, Castellani MS, et al. Circulating adipocytokines in non-diabetic and Type 1 diabetic children: relationship to insulin therapy, glycaemic control and pubertal development. Diabet Med 2006;23:660–5.10.1111/j.1464-5491.2006.01823.x Search in Google Scholar PubMed

22. Galler A, Gelbrich G, Kratzsch J, Noack N, Kapellen T, et al. Serum levels of adiponectin in children, adolescents and young adults with type 1 diabetes and the impact of age, gender, body mass index and metabolic control: a longitudinal study. Eur J Endocrinol 2007;157:481–9.10.1530/EJE-07-0250 Search in Google Scholar PubMed

23. Barnes MM, Curran-Everett D, Hamman RF, Maahs D, Mayer-Davis EJ, et al. Determinants of adiponectin levels in young people with type 1 diabetes. Diabet Med 2008;25:365–9.10.1111/j.1464-5491.2007.02374.x Search in Google Scholar PubMed

24. Kirino Y, Sei M, Kawazoe K, Minakuchi K, Sato Y. Plasma dipeptidyl peptidase 4 activity correlates with body mass index and the plasma adiponectin concentration in healthy young people. Endocr J 2012;59:949–53.10.1507/endocrj.EJ12-0158 Search in Google Scholar