GLP-1, the gut-brain, and brain-periphery axes.

International audienceGlucagon-like peptide 1 (GLP-1) is a gut hormone which directly binds to the GLP-1 receptor located at the surface of the pancreatic β-cells to enhance glucose-induced insulin secretion. In addition to its pancreatic effects, GLP-1 can induce metabolic actions by interacting with its receptors expressed on nerve cells in the gut and the brain. GLP-1 can also be considered as a neuropeptide synthesized by neuronal cells in the brain stem that release the peptide directly into the hypothalamus. In this environment, GLP-1 is assumed to control numerous metabolic and cardiovascular functions such as insulin secretion, glucose production and utilization, and arterial blood flow. However, the exact roles of these two locations in the regulation of glucose homeostasis are not well understood. In this review, we highlight the latest experimental data supporting the role of the gut-brain and brain-periphery axes in the control of glucose homeostasis. We also focus our attention on the relevance of β-cell and brain cell targeting by gut GLP-1 for the regulation of glucose homeostasis. In addition to its action on β-cells, we find that understanding the physiological role of GLP-1 will help to develop GLP-1-based therapies to control glycemia in type 2 diabetes by triggering the gut-brain axis or the brain directly. This pleiotropic action of GLP-1 is an important concept that may help to explain the observation that, during their treatment, type 2 diabetic patients can be identified as 'responders' and 'non-responders'

The Interplay of Endothelial P2Y Receptors in Cardiovascular Health: From Vascular Physiology to Pathology

The endothelium plays a key role in blood vessel health. At the interface of the blood, it releases several mediators that regulate local processes that protect against the development of cardiovascular disease. In this interplay, there is increasing evidence for a role of extracellular nucleotides and endothelial purinergic P2Y receptors (P2Y-R) in vascular protection. Recent advances have revealed that endothelial P2Y1-R and P2Y2-R mediate nitric oxide-dependent vasorelaxation as well as endothelial cell proliferation and migration, which are processes involved in the regeneration of damaged endothelium. However, endothelial P2Y2-R, and possibly P2Y1-R, have also been reported to promote vascular inflammation and atheroma development in mouse models, with endothelial P2Y2-R also being described as promoting vascular remodeling and neointimal hyperplasia. Interestingly, at the interface with lipid metabolism, P2Y12-R has been found to trigger HDL transcytosis through endothelial cells, a process known to be protective against lipid deposition in the vascular wall. Better characterization of the role of purinergic P2Y-R and downstream signaling pathways in determination of the endothelial cell phenotype in healthy and pathological environments has clinical potential for the prevention and treatment of cardiovascular diseases

Le vieillissement et nutrition des personnes à risque

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

A role for the gut-to-brain GLP-1-dependent axis in the control of metabolism.

International audienceOver the past years tremendous amounts of clinical and fundamental data have been generated about GLP-1 and related therapeutic strategies for the treatment of type 2 diabetes. However, the cellular and physiological mechanisms through which GLP-1 is secreted, controls glycemia, and behaves as a therapeutic agent are certainly unclear. This is due to the dogma that proposes that upon glucose absorption GLP-1 is secreted into the hepatoportal blood flow, binds to its receptor at the surface of the insulin secreting beta cells, and triggers the secretion of insulin to control glycemia. However, these events have never been demonstrated sequentially for the control of glycemia. This conclusion is supported by a growing number of evidences that point out that the enteric and the central nervous systems are main actors in the control of GLP-1 action. This involves the triggering of the gut-to-brain and to periphery axis where nutrients regulate the release of GLP-1 and activate the tightly regulated enteric and cerebral neuronal circuits. These integrate and redistribute the GLP-1-dependent signals toward numerous targeted tissues. We will review some of them

Détermination des mécanismes moléculaires impliqués dans la régulation coordonnée de la sensibilité à l'insuline et du flux artériel fémoral par l'insuline et le GLP-1 cérébral chez la souris diabétique

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

La dermatoporose

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Analyse rétrospective des effets indésirables de l'infliximab sur une cohorte de patients de rhumatologie

Infliximab is a chimeric monoclonal antibody against human tumor necrosis factor-a (TNF-a). The aim of the present survey was to assess retrospectively adverse drug reactions (ADRs) in a rheumatology department of the Toulouse University Hospital. During a period of 3 years, 79 patients were included in the study and suffer from arthritis rheumatoid (n=69), ankylosing spondylitis (n= 8) and psoriasic arthritis (n=2). However 159 expected ADRs were occurred in 56 patients (70,9%) [mean age 52,2 +-14,3] of which 13 ADRs (7,5%, n=12) were classified as serious . In 15 patients, they required the discontinuation of infliximab. We identified mainly infectious (121ADRs, n=47), allergic (16 ADRs, n= 10) and cardiovascular (8 ADRs, n= 4) effects. There are five therapeutic inefficacities in five cases. The incidence of respiratory and cutaneous infectious ADRs was 40,5% and 22,7% respectively. Our data allowed a quantitative and qualitative assessment of infliximab ADRs on a limited number of subjects.TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Les compléments nutritionnels oraux et le conseil à l'officine

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Le mélanome (dérégulation des voies de signalisations intracellulaires et développement des thérapies ciblées)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF