The artificial pancreas: is it important to understand how the β cell controls blood glucose?

It has been more than 7 years since the first fully automated closed-loop insulin delivery system that linked subcutaneous insulin delivery and glucose sensing was published. Since the initial report, the physiologic insulin delivery (PID) algorithm used to emulate the β cell has been modified from the original proportional-integral-derivative terms needed to fit the β cell's biphasic response to a hyperglycemic clamp to include terms emulating cephalic phase insulin release and the effect of insulin per se to inhibit insulin secretion. In this article, we compare the closed-loop glucose profiles obtained as each new term has been added, reassess the ability of the revised PID model to describe the β cells' insulin response to a hyperglycemic clamp, and look for the first time at its ability to describe the response to a hypoglycemic clamp.

Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction?

In both type 1 and type 2 diabetes, diabetic complications in target organs arise from chronic elevations of glucose. The pathogenic effect of high glucose, possibly in concert with fatty acids, is mediated to a significant extent via increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and subsequent oxidative stress. ROS and RNS directly oxidize and damage DNA, proteins, and lipids.

Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes.

In both type 1 and type 2 diabetes, the late diabetic complications in nerve, vascular endothelium, and kidney arise from chronic elevations of glucose and possibly other metabolites including free fatty acids (FFA). Recent evidence suggests that common stress-activated signaling pathways such as nuclear factor-kappaB, p38 MAPK, and NH2-terminal Jun kinases/stress-activated protein kinases underlie the development of these late diabetic complications. In addition, in type 2 diabetes, there is evidence that the activation of these same stress pathways by glucose and possibly FFA leads to both insulin resistance and impaired insulin secretion.