GLP-1 response to sequential mixed meals: Influence of insulin resistance

Eleni Rebelos, Brenno Astiarraga, Roberto Bizzotto, Andrea Mari, Maria Laura Manca, Alex Gonzalez, Armando J Mendez, Claudia Martinez, Barry Hurwitz, Ele Ferrannini

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Abstract

Previous work has shown that potentiation of insulin release is impaired in non-diabetic insulin resistance; we tested the hypothesis that this defect may be related to altered glucagon-like peptide-1 (GLP-1) release. On consecutive days, 82 non-diabetic individuals, classified as insulin sensitive (IS, n=41) or insulin resistant (IR, n=41) by the euglycaemic clamp, were given two sequential mixed meals with standard (75 g, LCD) or double (150 g, HCD) carbohydrate content. Plasma glucose, insulin, C-peptide, non-esterified fatty acids (NEFA) and GLP-1 concentrations were measured; ß-cell function (glucose sensitivity and potentiation) was resolved by mathematical modelling. Fasting GLP-1 levels were higher in IR than IS (by 15%, P=0.006), and reciprocally related to insulin sensitivity after adjustment for sex, age, fat mass, fasting glucose or insulin concentrations. Mean postprandial GLP-1 responses were tightly correlated with fasting GLP-1, were higher for the second than the first meal, and higher in IR than IS subjects but only with LCD. In contrast, incremental GLP-1 responses were higher during (i) the second than the first meal, (ii) on HCD than LCD, and (iii) significantly smaller in IR than IS independently of meal and load. Potentiation of insulin release was markedly reduced in IR vs IS across meal and carbohydrate loading. In the whole dataset, incremental GLP-1 was directly related to potentiation, and both were inversely related to mean NEFA concentrations. We conclude that (a) raised GLP-1 tone may be inherently linked with a reduced GLP-1 response and (b) defective post-meal GLP-1 response may be one mechanism for impaired potentiation of insulin release in insulin resistance.

Original languageEnglish (US)
Pages (from-to)2901-2910
Number of pages10
JournalClinical Science
Volume131
Issue number24
DOIs
StatePublished - Dec 15 2017

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Glucagon-Like Peptide 1
Meals
Insulin Resistance
Insulin
Fasting
Glucose
Fatty Acids
Glucose Clamp Technique
C-Peptide
Fats
Carbohydrates

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Rebelos, E., Astiarraga, B., Bizzotto, R., Mari, A., Manca, M. L., Gonzalez, A., ... Ferrannini, E. (2017). GLP-1 response to sequential mixed meals: Influence of insulin resistance. Clinical Science, 131(24), 2901-2910. https://doi.org/10.1042/CS20171409

GLP-1 response to sequential mixed meals : Influence of insulin resistance. / Rebelos, Eleni; Astiarraga, Brenno; Bizzotto, Roberto; Mari, Andrea; Manca, Maria Laura; Gonzalez, Alex; Mendez, Armando J; Martinez, Claudia; Hurwitz, Barry; Ferrannini, Ele.

In: Clinical Science, Vol. 131, No. 24, 15.12.2017, p. 2901-2910.

Research output: Contribution to journalArticle

Rebelos, E, Astiarraga, B, Bizzotto, R, Mari, A, Manca, ML, Gonzalez, A, Mendez, AJ, Martinez, C, Hurwitz, B & Ferrannini, E 2017, 'GLP-1 response to sequential mixed meals: Influence of insulin resistance', Clinical Science, vol. 131, no. 24, pp. 2901-2910. https://doi.org/10.1042/CS20171409
Rebelos E, Astiarraga B, Bizzotto R, Mari A, Manca ML, Gonzalez A et al. GLP-1 response to sequential mixed meals: Influence of insulin resistance. Clinical Science. 2017 Dec 15;131(24):2901-2910. https://doi.org/10.1042/CS20171409
Rebelos, Eleni ; Astiarraga, Brenno ; Bizzotto, Roberto ; Mari, Andrea ; Manca, Maria Laura ; Gonzalez, Alex ; Mendez, Armando J ; Martinez, Claudia ; Hurwitz, Barry ; Ferrannini, Ele. / GLP-1 response to sequential mixed meals : Influence of insulin resistance. In: Clinical Science. 2017 ; Vol. 131, No. 24. pp. 2901-2910.
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