Gastrin: a new branch of the gastropancreatic axis that can explain the effect of sleeve gastrectomy on glucose metabolism.

BACKGROUND: Among bariatric techniques, sleeve gastrectomy (SG) stands out owing to its efficiency. The role of the stomach as a secretory organ of many substances, such as gastrin, related to insulin secretion is well known. Gastrin induces insulin release in isolated pancreatic islets, limiting somatostatin-14 intraislet release, and has been associated with blood glucose level improvement in diabetic models after SG. SG involves gastric resection along the greater curvature. This study aimed to determine the role of gastrin in glucose metabolism improvement after SG with the aid of the gastrin antagonist netazepide. METHODS: In 12 sham-operated, 12 SG-operated, and 12 SG-operated/netazepide-treated Wistar rats, we compared medium- and long-term plasma insulin, oral glucose tolerance test (OGTT) results, and plasma gastrin levels. In addition, gastrin expression was assessed in the gastric remnant, and the beta-cell mass was measured. RESULTS: SG induced a medium-term elevation of the insulin response and plasma gastrin levels without modification of the OGTT results. However, long-term depletion of the insulin response with elevated OGTT areas under the curve and plasma gastrin levels appeared after SG. Netazepide prevented the SG effect on these parameters. Gastrin tissue expression was greater in SG animals than in SG/netazepide-treated or control animals. The beta-cell mass was lower in the SG group than in the control or SG/netazepide group. CONCLUSION: Gastrin plays a central role in glucose improvement after SG. It stimulates a medium-term strong insulin response but also causes long-term beta-cell mass depletion and a loss of insulin response. These effects are prevented by gastrin antagonists such as netazepide.

Metaloproteinasas de matriz: su implicación en las enfermedades vasculares periféricas / Matrix metalloproteases: their involvement in peripheral vascular diseases

Objetivos. Aportar los conceptos básicos sobre la estructura y la función de las metaloproteinasas de matriz (MMP) y exponer de forma resumida la información bibliográfica actualizada sobre su implicación en las enfermedades vasculares periféricas. Desarrollo. La matriz extracelular desempeña un papel esencial en el mantenimiento de la integridad del sistema cardiovascular. En condiciones normales, las fibras de elastina y colágeno resisten la desestructuración espontánea y pueden degradarse por las MMP. Las MMP son enzimas proteolíticas que se encargan de la remodelación de la matriz extracelular y, en su conjunto, pueden degradar todos los constituyentes de ésta. Diversas publicaciones han demostrado la implicación de las MMP en algunas vasculopatías, especialmente en la formación de aneurismas, la hiperplasia intimal, la ateroesclerosis y las úlceras venosas, lo que ha llevado a estudiar la inhibición de las MMP en modelos experimentales de enfermedades vasculares. Conclusiones. Las MMP, por su capacidad de degradar los componentes de la matriz extracelular, son enzimas que desempeñan un papel importante en procesos biológicos y patológicos múltiples, entre ellos algunas enfermedades vasculares. Los avances en el conocimiento de sus mecanismos de activación, la especificidad de sustratos y los mecanismos de inhibición por los inhibidores tisulares de las MMP han permitido el diseño de inhibidores sintéticos de las metaloproteinasas que probablemente permitan diseñar en el futuro nuevas estrategias terapéuticas para combatir dichas enfermedades

To report on the fundamental concepts concerning the structure and function of metalloproteases and to offer a brief summary of the latest data from the literature about the involvement of matrix metalloproteases (MMPs) in peripheral vascular diseases. DEVELOPMENT. The extracellular matrix plays an essential role in maintaining the integrity of the cardiovascular system. Under normal conditions, elastin and collagen fibres withstand spontaneous destructuring and can be degraded by MMPs. MMPs are proteolytic enzymes that are responsible for remodelling the extracellular matrix and, taken as a whole, can degrade all its components. Several publications have demonstrated the involvement of MMPs in certain vascular diseases, especially in the formation of aneurysms, intimal hyperplasias, atherosclerosis and venous ulcers, and this has led researchers to study the inhibition of MMPs in experimental models of vascular diseases. CONCLUSIONS. Owing to their capacity to degrade the components of the extracellular matrix, MMPs are enzymes that play an important role in numerous biological and pathological processes, including some vascular diseases. The progress being made in our understanding of its mechanisms of action, substrate specificity and the mechanisms of inhibition used by the tissue inhibitors of MMPs has enabled us to design synthetic metalloprotease inhibitors that will probably make it possible in the future to design new therapeutic strategies with which to fight these diseases