Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients
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.
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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.”
From Gut mechanisms linking intestinal sweet sensing to glycemic control (2018) · cites this paper as [67]
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 )”
From Pharmacologic inhibition of somatostatin receptor 2 to restore glucagon counterregulation in diabetes (2024) · cites this paper as Toft-Nielsen et al., 2001
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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
- Publisher
- The Endocrine Society
- 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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