Lipopolysaccharides-mediated increase in glucose-stimulated insulin secretion: Involvement of the glucagon-like peptide 1 (GLP1) pathway.

Anh Thoai Nguyen 1 Stéphane Mandard 1 Cédric Dray 2 Valérie Deckert 1 Philippe Valet 2 Philippe Besnard 1 Daniel Drucker 3 Laurent Lagrost 1 Jacques Grober 1, *
* Auteur correspondant
1 LNC - Lipides - Nutrition - Cancer (U866)
2 I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
3 Department of Medicine
Abstract : : Lipopolysaccharides (LPS) of the cell wall of Gram (-) bacteria trigger inflammation, which is associated with marked changes in glucose metabolism. Hyperglycemia is frequently observed during bacterial infection and it is a marker of a poor clinical outcome in critically ill patients. The aim of the present study was to investigate the effect of an acute injection or continuous infusion of LPS on experimentally-induced hyperglycemia in wild-type and genetically-engineered mice. The acute injection of a single dose of LPS produced an increase in glucose disposal and glucose-stimulated insulin secretion (GSIS). Continuous infusion of LPS through mini-osmotic pumps was also associated with increased GSIS. Finally, manipulation of LPS detoxification by knocking out the plasma phospholipid transfer protein (PLTP) led to increased glucose disposal and GSIS. Overall, glucose tolerance and GSIS tests supported the hypothesis that mice treated with LPS develop glucose-induced hyperinsulinemia. The effects of LPS on glucose metabolism were significantly altered as a result of either the accumulation or antagonism of glucagon-like peptide 1 (GLP1). Complementary studies in wild-type and GLP1-R knockout mice further implicated the GLP1R-dependent pathway in mediating the LPS-mediated changes in glucose metabolism. Hence, enhanced GLP1 secretion and action underlies the development of glucose-mediated hyperinsulinemia associated with endotoxemia.
keyword : Lipopolysaccharides GLP-1 Glucose-Induced Insulin secretion
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Article dans une revue
Diabetes, American Diabetes Association, 2014, 63 (2), pp.471-82. 〈10.2337/db13-0903〉
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Anh Thoai Nguyen, Stéphane Mandard, Cédric Dray, Valérie Deckert, Philippe Valet, et al.. Lipopolysaccharides-mediated increase in glucose-stimulated insulin secretion: Involvement of the glucagon-like peptide 1 (GLP1) pathway.. Diabetes, American Diabetes Association, 2014, 63 (2), pp.471-82. 〈10.2337/db13-0903〉. 〈inserm-00880061〉

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