title: Alteration of hypothalamic glucose and lactate sensing in 48h hyperglycemic rats.
abstract: Hypothalamic detection of nutrients is involved in the control of energy metabolism and is altered in metabolic disorders. Although hypothalamic detection of blood lactate lowers hepatic glucose production and food intake, it is unknown whether it also modulates insulin secretion. To address this, a lactate injection via the right carotid artery (cephalad) was performed in Wistar rats. This triggered a transient increase in insulin secretion. Rats made hyperglycemic for 48h exhibited prolonged insulin secretion in response to a glucose injection via the carotid artery, but lactate injection induced two types of responses: half of the HG rats showed no difference compared to controls and the other half had markedly decreased insulin secretion. Astroglial monocarboxylates transporters MCT1 and MCT4 isoforms transfer lactate from blood to astrocytes and release lactate to the extracellular space, whilst the neuronal MCT2 isoform permits neuronal lactate uptake. We found that astroglial MCT1 and MCT4, and neuronal MCT2 protein levels in the medio-basal hypothalamus (MBH) were not modified by 48h-hyperglycemia. Together, these results indicate that hypothalamic sensing of circulating lactate triggers insulin secretion. Both glucose and lactate sensing are altered in a model of hyperglycemia, without alteration of MBH MCTs protein levels.
authors.affiliation: CNRS, UMR 6265, CSGA, F-21000 Dijon, France; INRA, UMR1324, CSGA, F-21000 Dijon, France; Université de bourgogne, CSGA, F-21000 Dijon, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Allard
authors.forename: Lionel
authors.initials: L
authors.lastname: Carneiro
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Collins
authors.forename: Chloé
authors.initials: C
authors.lastname: Chrétien
authors.forename: Sylvie
authors.initials: S
authors.lastname: Grall
authors.forename: Luc
authors.initials: L
authors.lastname: Pénicaud
authors.forename: Corinne
authors.initials: C
authors.lastname: Leloup
mesh_terms: D000818:Animals; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006943:Hyperglycemia / Q000378:metabolism*; D007031:Hypothalamus / Q000098:blood supply / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D019344:Lactic Acid / Q000097:blood* / Q000494:pharmacology; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000378:metabolism; D013997:Time Factors; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D005947:Glucose; D007328:Insulin; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C516342:Slc16a3 protein, rat; C091633:Slc16a7 protein, rat