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Antidiabetic actions of endogenous and exogenous GLP-1 in type 1 diabetic patients with and without residual ?-cell function.


ABSTRACT: 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 ?-cell function.Eight type 1 diabetic patients with (T1D+), eight without (T1D-) residual ?-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.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.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 ?-cell function. Endogenous GLP-1 regulates postprandial glucose excursions by modulating glucagon levels, GE, and ?-cell responsiveness to glucose. Long-term effects of GLP-1 in type 1 diabetic patients should be investigated in future clinical trials.

SUBMITTER: Kielgast U 

PROVIDER: S-EPMC3292336 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Antidiabetic actions of endogenous and exogenous GLP-1 in type 1 diabetic patients with and without residual β-cell function.

Kielgast Urd U   Holst Jens J JJ   Madsbad Sten S  

Diabetes 20110325 5


<h4>Objective</h4>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.<h4>Research design and methods</h4>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  ...[more]

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