Postprandial incretin and islet hormone responses and dipeptidyl-peptidase 4 enzymatic activity in patients with maturity onset diabetes of the young.

Autor:	Østoft SH; Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark s.ostoft@dadlnet.dk., Bagger JI; Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark., Hansen T; Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark., Hartmann B; Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark., Pedersen O; Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark., Holst JJ; Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark., Knop FK; Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark., Vilsbøll T; Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic ResearchUniversity of Copenhagen, Copenhagen, DenmarkFaculty of Health SciencesUniversity of Southern Denmark, Odense, Denmark.
Jazyk:	angličtina
Zdroj:	European journal of endocrinology [Eur J Endocrinol] 2015 Aug; Vol. 173 (2), pp. 205-15. Date of Electronic Publication: 2015 May 07.
DOI:	10.1530/EJE-15-0070
Abstrakt:	Objective: The role of the incretin hormones in the pathophysiology of maturity onset diabetes of the young (MODY) is unclear. Design: We studied the postprandial plasma responses of glucagon, incretin hormones (glucagon-like peptide 1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP)) and dipeptidyl-peptidase 4 (DPP4) enzymatic activity in patients with glucokinase (GCK) diabetes (MODY2) and hepatocyte nuclear factor 1α (HNF1A) diabetes (MODY3) as well as in matched healthy individuals (CTRLs). Subjects and Methods: Ten patients with MODY2 (mean age ± S.E.M. 43 ± 5 years; BMI 24 ± 2 kg/m(2); fasting plasma glucose (FPG) 7.1 ± 0.3 mmol/l: HbA1c 6.6 ± 0.2%), ten patients with MODY3 (age 31 ± 3 years; BMI 24 ± 1 kg/m(2); FPG 8.9 ± 0.8 mmol/l; HbA1c 7.0 ± 0.3%) and ten CTRLs (age 40 ± 5 years; BMI 24 ± 1 kg/m(2); FPG 5.1 ± 0.1 mmol/l; HbA1c 5.3 ± 0.1%) were examined with a liquid test meal. Results: All of the groups exhibited similar baseline values of glucagon (MODY2: 7 ± 1 pmol/l; MODY3: 6 ± 1 pmol/l; CTRLs: 8 ± 2 pmol/l, P=0.787), but patients with MODY3 exhibited postprandial hyperglucagonaemia (area under the curve (AUC) 838 ± 108 min × pmol/l) as compared to CTRLs (182 ± 176 min × pmol/l, P=0.005) and tended to have a greater response than did patients with MODY2 (410 ± 154 min × pmol/l, P=0.063). Similar peak concentrations and AUCs for plasma GIP and plasma GLP1 were observed across the groups. Increased fasting DPP4 activity was seen in patients with MODY3 (17.7 ± 1.2 mU/ml) vs CTRLs (13.6 ± 0.8 mU/ml, P=0.011), but the amount of activity was similar to that in patients with MODY2 (15.0 ± 0.7 mU/ml, P=0.133). Conclusion: The pathophysiology of MODY3 includes exaggerated postprandial glucagon responses and increased fasting DPP4 enzymatic activity but normal postprandial incretin responses both in patients with MODY2 and in patients with MODY3. (© 2015 European Society of Endocrinology.)
Databáze:	MEDLINE
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