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Effect of single-dose DPP-4 inhibitor sitagliptin on β-cell function and incretin hormone secretion after meal ingestion in healthy volunteers and drug-naïve, well-controlled type 2 diabetes subjects

Alsalim, Wathik LU ; Göransson, Olga LU ; Carr, Richard D.; Bizzotto, Roberto; Tura, Andrea; Pacini, Giovanni; Mari, Andrea and Ahrén, Bo LU (2018) In Diabetes, Obesity and Metabolism
Abstract

To explore the effects of a single dose of the DPP-4 inhibitor sitagliptin on glucose-standardized insulin secretion and β-cell glucose sensitivity after meal ingestion, 12 healthy and 12 drug-naïve, well-controlled type 2 diabetes (T2D) subjects (mean HbA1c 43mmol/mol, 6.2%) received sitagliptin (100mg) or placebo before a meal (525kcal). β-cell function was measured as the insulin secretory rate at a standardized glucose concentration and the β-cell glucose sensitivity (the slope between glucose and insulin secretory rate). Incretin levels were also monitored. Sitagliptin increased standardized insulin secretion, in both healthy and T2D subjects, compared to placebo, but without increasing β-cell glucose sensitivity. Sitagliptin also... (More)

To explore the effects of a single dose of the DPP-4 inhibitor sitagliptin on glucose-standardized insulin secretion and β-cell glucose sensitivity after meal ingestion, 12 healthy and 12 drug-naïve, well-controlled type 2 diabetes (T2D) subjects (mean HbA1c 43mmol/mol, 6.2%) received sitagliptin (100mg) or placebo before a meal (525kcal). β-cell function was measured as the insulin secretory rate at a standardized glucose concentration and the β-cell glucose sensitivity (the slope between glucose and insulin secretory rate). Incretin levels were also monitored. Sitagliptin increased standardized insulin secretion, in both healthy and T2D subjects, compared to placebo, but without increasing β-cell glucose sensitivity. Sitagliptin also increased active glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) and reduced total (reflecting the secretion) GIP, but not total GLP-1 levels. We conclude that a single dose of DPP-4 inhibition induces dissociated effects on different aspects of β-cell function and incretin hormones after meal ingestion in both healthy and well-controlled T2D subjects.

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author
organization
publishing date
type
Contribution to journal
publication status
in press
subject
keywords
Beta cell function, DPP-4 inhibitor, Incretins, Insulin secretion, Sitagliptin, Type 2 diabetes
in
Diabetes, Obesity and Metabolism
publisher
Wiley-Blackwell
external identifiers
  • scopus:85040723345
ISSN
1462-8902
DOI
10.1111/dom.13192
language
English
LU publication?
yes
id
dc12f31c-1b02-49d0-93ee-f7d1bb654345
date added to LUP
2018-02-26 17:14:47
date last changed
2018-06-24 05:20:43
@article{dc12f31c-1b02-49d0-93ee-f7d1bb654345,
  abstract     = {<p>To explore the effects of a single dose of the DPP-4 inhibitor sitagliptin on glucose-standardized insulin secretion and β-cell glucose sensitivity after meal ingestion, 12 healthy and 12 drug-naïve, well-controlled type 2 diabetes (T2D) subjects (mean HbA1c 43mmol/mol, 6.2%) received sitagliptin (100mg) or placebo before a meal (525kcal). β-cell function was measured as the insulin secretory rate at a standardized glucose concentration and the β-cell glucose sensitivity (the slope between glucose and insulin secretory rate). Incretin levels were also monitored. Sitagliptin increased standardized insulin secretion, in both healthy and T2D subjects, compared to placebo, but without increasing β-cell glucose sensitivity. Sitagliptin also increased active glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) and reduced total (reflecting the secretion) GIP, but not total GLP-1 levels. We conclude that a single dose of DPP-4 inhibition induces dissociated effects on different aspects of β-cell function and incretin hormones after meal ingestion in both healthy and well-controlled T2D subjects.</p>},
  author       = {Alsalim, Wathik and Göransson, Olga and Carr, Richard D. and Bizzotto, Roberto and Tura, Andrea and Pacini, Giovanni and Mari, Andrea and Ahrén, Bo},
  issn         = {1462-8902},
  keyword      = {Beta cell function,DPP-4 inhibitor,Incretins,Insulin secretion,Sitagliptin,Type 2 diabetes},
  language     = {eng},
  publisher    = {Wiley-Blackwell},
  series       = {Diabetes, Obesity and Metabolism},
  title        = {Effect of single-dose DPP-4 inhibitor sitagliptin on β-cell function and incretin hormone secretion after meal ingestion in healthy volunteers and drug-naïve, well-controlled type 2 diabetes subjects},
  url          = {http://dx.doi.org/10.1111/dom.13192},
  year         = {2018},
}