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

• Published in: Diabetes research and clinical practice 2008-01, Vol.79 (1), p.79-85
• Main Authors: McKillop, Aine M, Duffy, Nicola A, Lindsay, John R, O’Harte, Finbarr P.M, Bell, Patrick M, Flatt, Peter R
• Format: Article
• Language: English
• Subjects: Aged; Blood Glucose - metabolism; Body Mass Index; Creatinine - blood; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - diet therapy; Diabetes Mellitus, Type 2 - drug therapy; Diet, Diabetic; Dipeptidyl Peptidase 4 - blood; Dipeptidyl peptidase-IV; Endocrinology & Metabolism; Female; Glucagon-Like Peptide 1 - blood; Glucagon-like peptide-1; Glycated Hemoglobin A - metabolism; Humans; Hypoglycemic Agents - therapeutic use; Kinetics; Male; Middle Aged; Peptide Fragments - blood; Type 2 diabetes
• ISSN: 0168-8227; 1872-8227
• 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 (HbA1c 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 HbA1c ( 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.