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

Aine McKillop, Nicola A Duffy, John R Lindsay, Finbarr O'Harte, Patrick M Bell, Peter Flatt

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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) 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.
LanguageEnglish
Pages79-85
JournalDiabetes Research and Clinical Practice
Volume79
Issue number1
DOIs
Publication statusPublished - Jan 2008

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Dipeptidyl Peptidase 4
Glucagon-Like Peptide 1
Ireland
Type 2 Diabetes Mellitus
Healthy Volunteers
Hormones
Glucose
glucagon-like peptide 1 (7-36)amide
Enzymes
Population

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title = "Decreased dipeptidyl peptidase-IV activity and glucagon-like peptide-1(7-36)amide degradation in type 2 diabetic subjects",
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) 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.",
author = "Aine McKillop and Duffy, {Nicola A} and Lindsay, {John R} and Finbarr O'Harte and Bell, {Patrick M} and Peter Flatt",
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Decreased dipeptidyl peptidase-IV activity and glucagon-like peptide-1(7-36)amide degradation in type 2 diabetic subjects. / McKillop, Aine; Duffy, Nicola A; Lindsay, John R; O'Harte, Finbarr; Bell, Patrick M; Flatt, Peter.

In: Diabetes Research and Clinical Practice, Vol. 79, No. 1, 01.2008, p. 79-85.

Research output: Contribution to journalArticle

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AU - Duffy, Nicola A

AU - Lindsay, John R

AU - O'Harte, Finbarr

AU - Bell, Patrick M

AU - Flatt, Peter

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AB - 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) 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.

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DO - 10.1016/j.diabres.2007.08.001

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