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Cited by 137Diabetes Treatment and ManagementDiabetes Management and ResearchPancreatic function and diabetes

Antidiabetic Actions of Endogenous and Exogenous GLP-1 in Type 1 Diabetic Patients With and Without Residual β-Cell Function

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Kielgast, Urd, Holst, Jens J., Madsbad, Sten·2011·Diabetes
DOI 10.2337/db10-1790PMC PMC3292336
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Abstract

OBJECTIVE: To investigate the effect of exogenous as well as endogenous glucagon-like peptide 1 (GLP-1) on postprandial glucose excursions and to characterize the secretion of incretin hormones in type 1 diabetic patients with and without residual β-cell function. RESEARCH DESIGN AND METHODS: Eight type 1 diabetic patients with (T1D+), eight without (T1D−) residual β-cell function, and eight healthy matched control subjects were studied during a mixed meal with concomitant infusion of GLP-1 (1.2 pmol/kg/min), saline, or exendin 9-39 (300 pmol/kg/min). Before the meal, half dose of usual fast-acting insulin was injected. Plasma glucose (PG), glucagon, C-peptide, total GLP-1, intact glucose-dependent insulinotropic polypeptide (GIP), free fatty acids, triglycerides, and gastric emptying rate (GE) by plasma acetaminophen were measured. RESULTS: Incretin responses did not differ between patients and control subjects. Infusion of GLP-1 decreased peak PG by 45% in both groups of type 1 diabetic patients. In T1D+ patients, postprandial PG decreased below fasting levels and was indistinguishable from control subjects infused with saline. In T1D− patients, postprandial PG remained at fasting levels. GLP-1 infusion reduced GE and glucagon levels in all groups and increased fasting C-peptide in T1D+ patients and control subjects. Blocking endogenous GLP-1 receptor action increased endogenous GLP-1 secretion in all groups and increased postprandial glucose, glucagon, and GE in T1D+ and T1D− patients. The insulinogenic index (the ratio of insulin to glucose) decreased in T1D+ patients during blockade of endogenous GLP-1 receptor action. CONCLUSIONS: Type 1 diabetic patients have normal incretin responses to meals. In type 1 diabetic patients, exogenous GLP-1 decreases peak postprandial glucose by 45% regardless of residual β-cell function. Endogenous GLP-1 regulates postprandial glucose excursions by modulating glucagon levels, GE, and β-cell responsiveness to glucose. Long-term effects of GLP-1 in type 1 diabetic patients should be investigated in future clinical trials.

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  • GLP-1 might prove beneficial, with studies noting that this incretin decreased peak postprandial glucose by 45% regardless of residual β-cell function.

    “GLP-1 might also prove beneficial, with studies noting that this incretin decreased peak postprandial glucose by 45% regardless of residual β-cell function.101”

    From Type 1 diabetes (2014) · cites this paper as [101]

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Authors
Kielgast, U., Holst, J. J., & Madsbad, S.
Affiliations
  • University of Copenhagen (DK)
  • Hvidovre Hospital (DK)
Corresponding author
Kielgast, Urd
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2011-04-23
Volume
60
Issue
5
Pages
1599-1607
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db10-1790
PMC
PMC3292336
OpenAlex
W2160945140
Cited by
137
References
11
Citations by year
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FWCI
10.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
glucagon-like peptide-1, type 1 diabetes, residual beta-cell function, postprandial blood glucose, incretin secretion, exendin-9-39, gastric emptying, glucagon, insulinogenic index, glucose-dependent insulinotropic polypeptide, C-peptide
MeSH terms
Adult, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 1, Female, Gastric Emptying, Gastric Inhibitory Polypeptide, Glucagon, Humans, Hypoglycemic Agents, Insulin, Male, Peptide Fragments, Triglycerides, Insulin-Secreting Cells, Glucagon-Like Peptide 1, Young Adult

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