Cited by 869Diabetes Treatment and ManagementPancreatic function and diabetesDiabetes Management and Research

Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients

Toft-Nielsen, Mai-Britt, Damholt, Mette B., Madsbad, Sten, Hilsted, Linda M., Hughes, Thomas E., Michelsen, Birgitte K., Holst, Jens J.·2001·The Journal of Clinical Endocrinology & Metabolism

Abstract

To elucidate the causes of the diminished incretin effect in type 2 diabetes mellitus we investigated the secretion of the incretin hormones, glucagon-like peptide-1 and glucose- dependent insulinotropic polypeptide and measured nonesterified fatty acids, and plasma concentrations of insulin, C peptide, pancreatic polypeptide, and glucose during a 4-h mixed meal test in 54 heterogeneous type 2 diabetic patients, 33 matched control subjects with normal glucose tolerance, and 15 unmatched subjects with impaired glucose tolerance. The glucagon-like peptide-1 response in terms of area under the curve from 0-240 min after the start of the meal was significantly decreased in the patients (2482 +/- 145 compared with 3101 +/- 198 pmol/liter.240 min; P = 0.024). In addition, the area under the curve for glucose-dependent insulinotropic polypeptide was slightly decreased. In a multiple regression analysis, a model with diabetes, body mass index, male sex, insulin area under the curve (negative influence), glucose-dependent insulinotropic polypeptide area under the curve (negative influence), and glucagon area under the curve (positive influence) explained 42% of the variability of the glucagon-like peptide-1 response. The impaired glucose tolerance subjects were hyperinsulinemic and generally showed the same abnormalities as the diabetic patients, but to a lesser degree. We conclude that the meal-related glucagon-like peptide-1 response in type 2 diabetes is decreased, which may contribute to the decreased incretin effect in type 2 diabetes.

Integrity signals

Registry

Crossref · 10.1210/jcem.86.8.7750

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55 of 55 references verified0 citation errors · 0 not checkable

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  • In type 2 diabetes, attenuated insulinotropic action of GIP and sometimes attenuated GLP-1 secretion contribute to impaired postprandial insulin secretion insufficient to maintain euglycaemia.

    “in type 2 diabetes, a markedly attenuated insulinotropic action of GIP (66) and, in some cases, attenuated secretion of GLP-1 (67), contribute to an impairment of postprandial insulin secretion, so that the latter is insufficient to maintain euglycaemia.”
  • People with obesity and/or T2D have impaired incretin release and/or function.

    “People with obesity and/or T2D have impaired incretin release ( Toft-Nielsen et al., 2001 ; Vilsbøll et al., 2001 ) and/or function ( Nauck et al., 1986 ; Muscelli et al., 2008 )”

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Authors
Toft-Nielsen, M.-B., Damholt, M. B., Madsbad, S., Hilsted, L. M., Hughes, T. E., Michelsen, B. K., & Holst, J. J.
Affiliations
  • University of Copenhagen (DK)
  • Novartis (United States) (US)
Corresponding author
Holst, Jens J.
Venue
The Journal of Clinical Endocrinology & Metabolism
Published
2001-08
Volume
86
Issue
8
Pages
3717-3723
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
OpenAlex
W2089304685
Cited by
869
References
55
Citations by year
2026: 11 · 2025: 16 · 2024: 20 · 2023: 19 · 2022: 24 · 2021: 24 · 2020: 21 · 2019: 36 · 2018: 30 · 2017: 31 · 2016: 38 · 2015: 48 · 2014: 47 · 2013: 64 · 2012: 43
FWCI
6.81
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Sundhed og Sygdom, Det Frie Forskningsråd
  • Novo Nordisk
  • Copenhagen Graduate School for Nanoscience and Nanotechnology
  • Lægeforeningen
  • Hvidovre Hospital
  • Novo Nordisk Fonden
  • Diabetesforeningen
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, type 2 diabetes, incretin effect, mixed meal tolerance test, impaired glucose tolerance, hyperinsulinemia, free fatty acids, pancreatic polypeptide, glucagon, body mass index, sex differences
MeSH terms
Analysis of Variance, Autoantibodies, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 2, Fasting, Fatty Acids, Nonesterified, Female, Gastric Inhibitory Polypeptide, Glucagon, Glutamate Decarboxylase, Glycated Hemoglobin, Humans, Insulin, Male, Middle Aged, Pancreatic Polypeptide, Peptide Fragments, Peptides, Protein Precursors, Reference Values, Glucose Intolerance, Glucagon-Like Peptide 1

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