O12 Implication de la Cx43 dans la détection hypothalamique du glucose

Introduction L'hypothalamus est fortement implique dans la regulation nerveuse de l'homeostasie glucidique. La detection de l'hyperglycemie par des neurones specialises declenche des reponses adaptees comme le maintien de la glycemie ou encore le rassasiement. Les astrocytes sont suspectes participer a la detection neuronale du glucose. Ils sont organises en reseaux et presentent un grand nombre de jonctions gap (JG) permettant le passage du glucose de la circulation sanguine vers les neurones. Ces JG sont formees majoritairement de connexine 43 (Cx43). Nous avons fait l'hypothese que les reseaux astrocytaires, via les Cx43 en particulier, participent a la detection hypothalamique du glucos…

Implication of Cx43 in hypothalamic detection of glucosis.

Meeting Abstract ; WOS: 000302819400014; International audience

Alteration of hypothalamic glucose sensing in high fat-high sucrose diet fed rats: early defects linked to mitochondrial dynamics and mROS signalling

Hypothalamic Astroglial Connexins are Required for Brain Glucose Sensing-Induced Insulin Secretion

Supplementary Information accompanies the paper on the Journal of Cerebral Blood Flow & Metabolism website; Hypothalamic glucose detection participates in maintaining glycemic balance, food intake, and thermogenesis. Although hypothalamic neurons are the executive cells involved in these responses, there is increasing evidence that astrocytes participate in glucose sensing (GS); however, it is unknown whether astroglial networking is required for glucose sensitivity. Astroglial connexins 30 and 43 (Cx30 and Cx43) form hexameric channels, which are apposed in gap junctions, allowing for the intercellular transfer of small molecules such as glucose throughout the astroglial networks. Here, we…

Importance of mitochondrial dynamin-related protein 1 in hypothalamic glucose sensitivity in rats.

International audience; AIMS: Hypothalamic mitochondrial reactive oxygen species (mROS)-mediated signaling has been recently shown to be involved in the regulation of energy homeostasis. However, the upstream signals that control this mechanism have not yet been determined. Here, we hypothesize that glucose-induced mitochondrial fission plays a significant role in mROS-dependent hypothalamic glucose sensing. RESULTS: Glucose-triggered translocation of the fission protein dynamin-related protein 1 (DRP1) to mitochondria was first investigated in vivo in hypothalamus. Thus, we show that intracarotid glucose injection induces the recruitment of DRP1 to VMH mitochondria in vivo. Then, expressio…

Alteration of hypothalamic glucose and lactate sensing in 48h hyperglycemic rats.

International audience; 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 comp…

Astrocytes and hypothalamic glucose sensing: metabolic role and involvement of astroglial connexins

The hypothalamus plays a pivotal role in the nervous control of glucose homeostasis. This area contains gluco-sensitive neurons. Some of them detect increases in glucose levels and regulate glucose homeostasis by stimulating insulin secretion or inhibiting food intake. It is widely accepted that astrocytes are metabolically coupled to neurons. Lactate, resulting from the metabolism of glucose by astrocytes, is transported via the monocarboxylate transporters (MCTs). In addition, gap junctions (GJ), that form networks within astrocytes, are essential to transfer glucose from the bloodstream to the active neurons. These astroglial GJ mainly consist of connexins 43 and 30 (Cxs).The aims of my …

032 Implication de la Cx43 dans le glucose-sensing hypothalamique

Introduction L’hypothalamus est fortement implique dans la regulation de l’homeostasie glucidique. Les variations de glycemie y sont detectees par des neurones specialises, notamment dans le noyau arque : on parle de « glucose-sensing » (GS). L’integration de cette information declenche une reponse adaptee afin de maintenir la glycemie stable. L’acheminement du glucose de la circulation aux neurones implique les astrocytes. Ces derniers forment un reseau via les jonctions gap (JG) qui permet le trafic de metabolites, dont le glucose, entre astrocytes et avec le milieu extracellulaire. Ces jonctions sont formees majoritairement de connexines 43 (Cx43), hemi-canaux fortement exprimes dans l’h…

Glucose and hypothalamic astrocytes: More than a fueling role?

Brain plays a central role in energy homeostasis continuously integrating numerous peripheral signals such as circulating nutrients, and in particular blood glucose level, a variable that must be highly regulated. Then, the brain orchestrates adaptive responses to modulate food intake and peripheral organs activity in order to achieve the fine tuning of glycemia. More than fifty years ago, the presence of glucose-sensitive neurons was discovered in the hypothalamus, but what makes them specific and identifiable still remains disconnected from their electrophysiological signature. On the other hand, astrocytes represent the major class of macroglial cells and are now recognized to support an…