Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance

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Elza Muscelli, Andrea Mari, Andrea Natali, Brenno D Astiarraga, Stefania Camastra, Silvia Frascerra, Jens Juul Holst, Ele Ferrannini

The mechanisms by which the enteroinsular axis influences beta-cell function have not been investigated in detail. We performed oral and isoglycemic intravenous (IV) glucose administration in subjects with normal (NGT; n = 11) or impaired glucose tolerance (IGT; n = 10), using C-peptide deconvolution to calculate insulin secretion rates and mathematical modeling to quantitate beta-cell function. The incretin effect was taken to be the ratio of oral to IV responses. In NGT, incretin-mediated insulin release [oral glucose tolerance test (OGTT)/IV ratio = 1.59 +/- 0.18, P = 0.004] amounted to 18 +/- 2 nmol/m(2) (32 +/- 4% of oral response), and its time course matched that of total insulin secretion. The beta-cell glucose sensitivity (OGTT/IV ratio = 1.52 +/- 0.26, P = 0.02), rate sensitivity (response to glucose rate of change, OGTT/IV ratio = 2.22 +/- 0.37, P = 0.06), and glucose-independent potentiation were markedly higher with oral than IV glucose. In IGT, beta-cell glucose sensitivity (75 +/- 14 vs. 156 +/- 28 pmol.min(-1).m(-2).mM(-1) of NGT, P = 0.01) and potentiation were impaired on the OGTT. The incretin effect was not significantly different from NGT in terms of plasma glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide responses, total insulin secretion, and enhancement of beta-cell glucose sensitivity (OGTT/IV ratio = 1.73 +/- 0.24, P = NS vs. NGT). However, the time courses of incretin-mediated insulin secretion and potentiation were altered, with a predominance of glucose-induced vs. incretin-mediated stimulation. We conclude that, under physiological circumstances, incretin-mediated stimulation of insulin secretion results from an enhancement of all dynamic aspects of beta-cell function, particularly beta-cell glucose sensitivity. In IGT, beta-cell function is inherently impaired, whereas the incretin effect is only partially affected.

Original languageEnglish
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Volume291
Issue number6
Pages (from-to)E1144-50
ISSN0193-1849
DOIs
Publication statusPublished - Dec 2006

    Research areas

  • Adult, Blood Glucose, Dose-Response Relationship, Drug, Fatty Acids, Nonesterified, Female, Gastric Inhibitory Polypeptide, Glucagon-Like Peptide 1, Glucose Intolerance, Glucose Tolerance Test, Hormones, Humans, Insulin, Insulin-Secreting Cells, Male, Middle Aged, Models, Statistical, Radioimmunoassay

ID: 132053121