Too much of a good thing : why it is bad to stimulate the beta cell to secrete insulin

In many countries, first- or second-line pharmacological treatment of patients with type 2 diabetes consists of sulfonylureas (such as glibenclamide [known as glyburide in the USA and Canada]), which stimulate the beta cell to secrete insulin. However, emerging evidence suggests that forcing the beta cell to secrete insulin at a time when it is struggling to cope with the demands of obesity and insulin resistance may accelerate its demise. Studies on families with persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI), the primary defect of which is hypersecretion of insulin, have shown that overt diabetes can develop later in life despite normal insulin sensitivity. In addition, in vitro experiments have suggested that reducing insulin secretion from islets isolated from patients with diabetes can restore insulin pulsatility and improve function. This article will explore the hypothesis that forcing the beta cell to hypersecrete insulin may be counterproductive and lead to dysfunction and death via mechanisms that may involve the endoplasmic reticulum and oxidative stress. We suggest that, in diabetes, therapeutic approaches should be targeted towards relieving the demand on the beta cell to secrete insulin.

A new design concept for knitted external vein-graft support mesh

Autologous vein-graft failure significantly limits the long-term efficacy of coronary artery bypass procedures. The major cause behind this complication is biomechanical mismatch between the vein and coronary artery. The implanted vein experiences a sudden increase (10-12 fold) in luminal pressures. The resulting vein over-distension or 'ballooning' initiates wall thickening phenomenon and ultimate occlusion. Therefore, a primary goal in improving the longevity of a coronary bypass procedure is to inhibit vein over-distension using mechanical constriction. The idea of using an external vein-graft support mesh has demonstrated sustained benefits and wide acceptance in experimental studies. Nitinol based knitted structures have offered more promising mechanical features than other mesh designs owing to their unique loosely looped construction. However, the conventional plain knit construction still exhibits limitations (radial compliance, deployment ease, flexibility, and bending stresses) which limit this design from proving its real clinical advantage. The new knitted mesh design presented in this study is based on the concept of composite knitting utilising high modulus (nitinol and polyester) and low modulus (polyurethane) material components. The experimental comparison of the new design with a plain knit design demonstrated significant improvement in biomechanical (compliance, flexibility, extensibility, viscoelasticity) and procedural (deployment limit) parameters. The results are indicative of the promising role of new mesh in restoring the lost compliance and pulsatility of vein-graft at high arterial pressures. This way it can assist in controlled vein-graft remodelling and stepwise restoration of vein mechanical homoeostasis. Also, improvement in deployment limit parameter offers more flexibility for a surgeon to use a wide range of vein diameters, which may otherwise be rendered unusable for a plain knit mesh.