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; β-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.
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Wheat germ agglutinin staining of the adult mouse heart transverse section. In their study, Diniz et al., shows microRNA-22 regulates dyslipidemia and energy expenditure. For more information please see pages 2885-2900. Image kindly provided by Da-Zhi Wang
Research Article|
December 04 2017
GLP-1 response to sequential mixed meals: influence of insulin resistance
Eleni Rebelos;
Eleni Rebelos
*
1Department of Clinical and Experimental Medicine, University of Pisa, 56122 Pisa, Italy
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Brenno Astiarraga;
Brenno Astiarraga
*
1Department of Clinical and Experimental Medicine, University of Pisa, 56122 Pisa, Italy
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Roberto Bizzotto;
Roberto Bizzotto
2CNR Institute of Neurosciences, Padua, Italy
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Andrea Mari;
Andrea Mari
2CNR Institute of Neurosciences, Padua, Italy
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Maria Laura Manca;
Maria Laura Manca
3Department of Mathematics, University of Pisa, Italy
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Alex Gonzalez;
Alex Gonzalez
4Behavioral Medicine Research Center, Miller School of Medicine, University of Miami, Miami, U.S.A.
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Armando Mendez;
Armando Mendez
5Division of Endocrinology, Diabetes and Metabolism, Miller School of Medicine, University of Miami, Miami, U.S.A.
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Claudia A. Martinez;
Claudia A. Martinez
6Cardiovascular Division, Miller School of Medicine, University of Miami, Miami, U.S.A.
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Barry E. Hurwitz;
Barry E. Hurwitz
7Behavioral Medicine Research Center and Division of Endocrinology, Diabetes and Metabolism, Miller School of Medicine, University of Miami, Miami, and Department of Psychology, University of Miami, Coral Gables, U.S.A.
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Ele Ferrannini
8CNR Institute of Clinical Physiology, Pisa, Italy
Correspondence: Ele Ferrannini (ferranni@ifc.cnr.it)
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Publisher: Portland Press Ltd
Received:
October 02 2017
Revision Received:
October 26 2017
Accepted:
November 01 2017
Accepted Manuscript online:
November 02 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (24): 2901–2910.
Article history
Received:
October 02 2017
Revision Received:
October 26 2017
Accepted:
November 01 2017
Accepted Manuscript online:
November 02 2017
Citation
Eleni Rebelos, Brenno Astiarraga, Roberto Bizzotto, Andrea Mari, Maria Laura Manca, Alex Gonzalez, Armando Mendez, Claudia A. Martinez, Barry E. Hurwitz, Ele Ferrannini; GLP-1 response to sequential mixed meals: influence of insulin resistance. Clin Sci (Lond) 15 December 2017; 131 (24): 2901–2910. doi: https://doi.org/10.1042/CS20171409
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