Liraglutide targets the gut microbiota and the intestinal immune system to regulate insulin secretion

Archive ouverte

Charpentier, Julie | Briand, François | Lelouvier, Benjamin | Servant, Florence | Azalbert, Vincent | Puel, Anthony | Christensen, Jeffrey | Waget, Aurélie | Branchereau, Maxime | Garret, Céline | Lluch, Jérome | Heymes, Christophe | Brousseau, Emmanuel | Burcelin, Rémy | Guzylack-Piriou, Laurence | Sulpice, Thierry | Grasset, Estelle

Edité par CCSD ; Springer Verlag -

International audience. Aims: Liraglutide controls type 2 diabetes (T2D) and inflammation. Gut microbiota regulates the immune system and causes at least in part type 2 diabetes. We here evaluated whether liraglutide regulates T2D through both gut microbiota and immunity in dysmetabolic mice.Methods: Diet-induced dysmetabolic mice were treated for 14 days with intraperitoneal injection of liraglutide (100 µg/kg) or with vehicle or Exendin 4 (10 µg/kg) as controls. Various metabolic parameters, the intestinal immune cells were characterized and the 16SrDNA gene sequenced from the gut. The causal role of gut microbiota was shown using large spectrum antibiotics and by colonization of germ-free mice with the gut microbiota from treated mice.Results: Besides, the expected metabolic impacts liraglutide treatment induced a specific gut microbiota specific signature when compared to vehicle or Ex4-treated mice. However, liraglutide only increased glucose-induced insulin secretion, reduced the frequency of Th1 lymphocytes, and increased that of TReg in the intestine. These effects were abolished by a concomitant antibiotic treatment. Colonization of germ-free mice with gut microbiota from liraglutide-treated diabetic mice improved glucose-induced insulin secretion and regulated the intestinal immune system differently from what observed in germ-free mice colonized with microbiota from non-treated diabetic mice.Conclusions: Altogether, our result demonstrated first the influence of liraglutide on gut microbiota and the intestinal immune system which could at least in part control glucose-induced insulin secretion.

Consulter en ligne

Suggestions

Du même auteur

CX3CR1 regulates gut microbiota and metabolism. A risk factor of type 2 diabetes

Archive ouverte | Pomié, Celine | CCSD

International audience. Objective: The intestinal microbiota to immune system crosstalk is a major regulator of metabolism and hence metabolic diseases. An impairment of the chemokine receptor CX3CR1, as a key regul...

Gut microbiota dysbiosis of type 2 diabetic mice impairs the intestinal daily rhythms of GLP-1 sensitivity

Archive ouverte | Grasset, Estelle | CCSD

International audience. The gut-brain-beta cell glucagon-like peptide-1 (GLP-1)-dependent axis and the clock genes both control insulin secretion. Evidence shows that a keystone of this molecular interaction could b...

A 3‐week nonalcoholic steatohepatitis mouse model shows elafibranor benefits on hepatic inflammation and cell death

Archive ouverte | Briand, François | CCSD

International audience. The long duration of animal models represents a clear limitation to quickly evaluate the efficacy of drugs targeting nonalcoholic steatohepatitis (NASH). We, therefore, developed a rapid mous...

Chargement des enrichissements...