title: Lipopolysaccharides-mediated increase in glucose-stimulated insulin secretion: involvement of the GLP-1 pathway.
abstract: Lipopolysaccharides (LPS) of the cell wall of gram-negative 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 current 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 (GLP-1). Complementary studies in wild-type and GLP-1 receptor knockout mice further implicated the GLP-1 receptor-dependent pathway in mediating the LPS-mediated changes in glucose metabolism. Hence, enhanced GLP-1 secretion and action underlies the development of glucose-mediated hyperinsulinemia associated with endotoxemia.
authors.affiliation: INSERM UMR866-LabEx LipSTIC, Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors.forename: Anh Thoai
authors.initials: AT
authors.lastname: Nguyen
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mandard
authors.forename: Cédric
authors.initials: C
authors.lastname: Dray
authors.forename: Valérie
authors.initials: V
authors.lastname: Deckert
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.forename: Philippe
authors.initials: P
authors.lastname: Besnard
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Drucker
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
authors.forename: Jacques
authors.initials: J
authors.lastname: Grober
mesh_terms: D000818:Animals; D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D008070:Lipopolysaccharides; D049294:Phospholipid Transfer Proteins; D018027:Receptors, Glucagon; C510091:phospholipid transfer protein, mouse; D052216:Glucagon-Like Peptide 1; D005947:Glucose