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Decreased dipeptidyl peptidase-IV activity and glucagon-like peptide-1(7-36)amide degradation in type 2 diabetic subjects

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McKillop, Aine, Duffy, Nicola A, Lindsay, John R, O'Harte, Finbarr, Bell, Patrick M and Flatt, Peter (2008) Decreased dipeptidyl peptidase-IV activity and glucagon-like peptide-1(7-36)amide degradation in type 2 diabetic subjects. DIABETES RESEARCH AND CLINICAL PRACTICE, 79 (1). pp. 79-85. [Journal article]

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DOI: 10.1016/j.diabres.2007.08.001

Abstract

Dipeptidyl peptidase (DPP-IV) rapidly metabolises hormones such as glucagon-like peptide-1(7-36)amide. This study evaluated circulating DPP-IV activity in type 2 diabetic patients in relation to GLP-1 degradation and metabolic control. Blood samples were collected from type 2 diabetic patients in three main categories: good glycaemic control (HbA(1c) <7%, upper limit of non-diabetic range), moderate glycaemic control (HbA(1c) 7-9%) and poor glycaemic control (HbA(1c) >9%). Age- and sex-matched non-diabetic subjects were used as controls. Circulating DPP-IV activity of healthy control subjects was 22.5 +/- 0.7 nmol/ml/min (n = 70). In the combined groups of type 2 diabetic subjects, circulating DPP-IV activity was significantly decreased at 18.1 +/- 0.7 nmol/ml/min (p < 0.001, n = 54). DPP-IV activity was negatively correlated with both glucose (p < 0.01) and HbA(1c) (p < 0.01) in this population. Furthermore, DPP-IV activity was reduced 1.2-fold (p < 0.01, n = 25), 1.3-fold (p < 0.001, n = 19) and 1.3-fold (p < 0.05, n =10) in good, moderate and poorly controlled diabetic groups, 18.7 +/- 1.0, 17.4 +/- 1.4 and 18.0 +/- 1.5 nmol/ml/min, respectively. Degradation of GLP-1 by in vitro incubation with pooled plasma samples from healthy and type 2 diabetic subjects revealed decreased degradation to the inactive metabolite, GLP-1(9-36), in the diabetic group. These data indicate decreased DPP-IV activity and GLP-1 degradation in type 2 diabetes. DPP-IV enzyme activity appears to be depressed in response to poor glycaemic control. (c). 2007 Elsevier Ireland Ltd. All rights reserved.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:2921
Deposited By:Professor Peter Flatt
Deposited On:17 Dec 2009 11:13
Last Modified:23 Jun 2011 16:31

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