16 research outputs found
The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation
The ability to ensure continuous availability of energy despite highly variable
supplies in the environment is a major determinant of the survival of all
species. In higher organisms, including mammals, the capacity to efficiently
store excess energy as triglycerides in adipocytes, from which stored energy
could be rapidly released for use at other sites, was developed. To orchestrate
the processes of energy storage and release, highly integrated systems operating
on several physiological levels have evolved. The adipocyte is no longer
considered a passive bystander, because fat cells actively secrete many members
of the cytokine family, such as leptin, tumor necrosis factor-alpha, and
interleukin-6, among other cytokine signals, which influence peripheral fuel
storage, mobilization, and combustion, as well as energy homeostasis. The
existence of a network of adipose tissue signaling pathways, arranged in a
hierarchical fashion, constitutes a metabolic repertoire that enables the
organism to adapt to a wide range of different metabolic challenges, such as
starvation, stress, infection, and short periods of gross energy excess
Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk
An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition