NDLI: Glucose-lowering effect of the DPP-4 inhibitor sitagliptin after glucose and non-glucose macronutrient ingestion in non-diabetic subjects.

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Glucose-lowering effect of the DPP-4 inhibitor sitagliptin after glucose and non-glucose macronutrient ingestion in non-diabetic subjects.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ohlsson, L. Alsalim, W. Carr, R. D. Tura, A. Pacini, G. Mari, A. Ahrén, B.
Description	Country affiliation: Sweden Author Affiliation: Ohlsson L ( Department of Clinical Sciences Lund, Lund University, Lund, Sweden.)
Abstract	AIM: Recent studies suggest that the incretin concept is not restricted to glucose ingestion but relevant also after non-glucose macronutrient administration. We therefore hypothesized that raising incretin hormones reduces circulating glucose after both glucose and non-glucose macronutrient ingestion in healthy subjects. METHODS: Twelve healthy subjects received the dipeptidyl peptidase-4 inhibitor sitagliptin (100 mg) or placebo before ingestion of glucose, fat (olive oil) or protein mix in equicaloric amounts (8 kcal/kg) plus paracetamol (1.5 g). The 120-min areas under curve (AUC) of intact glucagon-like peptide-1 (GLP-1), glucose, insulin, C-peptide, glucagon and paracetamol, and model-derived insulin secretion rate (ISR), insulin sensitivity, insulin clearance and glucose absorption were measured. RESULTS: The increased plasma intact GLP-1 levels after each macronutrient was augmented by sitagliptin. This was associated with a robust lowering of glucose: glucose excursion after oral glucose was diminished, and glucose fell below baseline after oral fat and protein. In spite of lower glucose, AUCC -peptide and ISR did not differ significantly between sitagliptin and placebo after any macronutrient. AUCglucagon , insulin sensitivity and insulin clearance were also not different between sitagliptin and placebo. Glucose absorption after oral glucose was reduced by sitagliptin, whereas AUCparacetamol was not statistically different between sitagliptin and placebo. CONCLUSIONS: Physiological elevation of intact GLP-1 levels after ingestion of glucose and non-glucose macronutrients is robustly glucose-lowering in healthy subjects. Hence, the incretin concept is not restricted to glucose ingestion in normal physiology. The glucose-lowering action of sitagliptin at these low glucose levels in healthy subjects may have complex mechanisms, involving both islet-dependent and islet-independent mechanisms.
File Format	HTM / HTML
ISSN	14628902
Issue Number	6
Volume Number	15
e-ISSN	14631326
Journal	Diabetes, Obesity and Metabolism
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2013-06-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Metabolism Discipline Endocrinology Discipline Pharmacology Discipline Diabetology Blood Glucose Drug Effects Dietary Fats Administration & Dosage Dietary Proteins Dipeptidyl-peptidase Iv Inhibitors Insulin Secretion Pyrazines Triazoles Adult Metabolism Glucose Tolerance Test Humans Insulin Resistance Physiology Insulin-secreting Cells Male Micronutrients Sitagliptin Phosphate Treatment Outcome Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Endocrinology, Diabetes and Metabolism Internal Medicine Endocrinology

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