Minimal state models for ionic channels involved in glucagon secretion

Pancreatic alpha cells synthesize and release glucagon. This hormone along with insulin, preserves blood glucose levels within a physiological range. During low glucose levels, alpha cells exhibit electrical activity related to glucagon secretion. In this paper, we introduce minimal state models for those ionic channels involved in this electrical activity in mice alpha cells. For estimation of model parameters, we use Monte Carlo algorithms to fit steadystate channel currents. Then, we simulate dynamic ionic currents following experimental protocols. Our aims are 1) To understand the individual ionic channel functioning and modulation that could affect glucagon secretion, and 2) To simulate ionic currents actually measured in voltage-clamp alpha-cell experiments in mice. Our estimations indicate that alpha cells are highly permeable to sodium and potassium which mainly manage action potentials. We have also found that our estimated N-type calcium channel population and density in alpha cells is in good agreement to those reported for L-type calcium channels in beta cells. This finding is strongly relevant since both, L-type and N-type calcium channels, play a main role in insulin and glucagon secretion, respectively

Physiologic Characterization of Type 2 Diabetes–Related Loci

For the past two decades, genetics has been widely explored as a tool for unraveling the pathogenesis of diabetes. Many risk alleles for type 2 diabetes and hyperglycemia have been detected in recent years through massive genome-wide association studies and evidence exists that most of these variants influence pancreatic β-cell function. However, risk alleles in five loci seem to have a primary impact on insulin sensitivity. Investigations of more detailed physiologic phenotypes, such as the insulin response to intravenous glucose or the incretion hormones, are now emerging and give indications of more specific pathologic mechanisms for diabetes-related risk variants. Such studies have shed light on the function of some loci but also underlined the complex nature of disease mechanism. In the future, sequencing-based discovery of low-frequency variants with higher impact on intermediate diabetes-related traits is a likely scenario and identification of new pathways involved in type 2 diabetes predisposition will offer opportunities for the development of novel therapeutic and preventative approaches

Optical coherence tomography.

Optical coherence tomography (OCT) is a recently developed technology capable of micron-scale imaging. Its high resolution (10-20 microm) makes intravascular OCT imaging the most interesting method for assessing atherosclerotic plaque microstructure in patients suffering from coronary artery disease. OCT allowed measurement of the thickness of the plaque fibrous cap, as well as identification of intima, media, and external elastic membrane in patients with normal coronary arteries. However, significant limitations still exist, including poor penetration in non-transparent tissue. The aim of this review is to give an update on OCT on the basis of the existing literature, with an overview of the strong and weak features of this technique

Effect of percutaneous coronary intervention on coronary blood flow at rest in myocardial sites remote from the intervention site in patients with stable angina pectoris.

Little is known about changes in myocardial perfusion of myocardial regions supplied by angiographically normal or near-normal coronary arteries after percutaneous coronary intervention (PCI) of the target lesion. The purpose of this study was to assess the effect of PCI on coronary blood flow at rest in sites remote from the PCI. We studied 85 patients who underwent successful elective PCI for stable angina. We used the Thrombolysis In Myocardial Infarction frame count to provide a simple continuous index of coronary flow and myocardial perfusion in the target and nontarget arteries. Coronary artery diameters of nontarget vessels did not significantly differ before and after PCI and at 6 months' follow-up. At baseline, the greater the percent diameter stenosis in the target artery, the slower the flow in the target (r = 0.22, p <0.01) and nontarget arteries (r = 0.28, p <0.01). Relief of stenosis using PCI did not account for simultaneous changes in epicardial coronary blood flow of the nontarget artery. After 6 months, coronary blood flow improved in both the target (p <0.05) and nontarget arteries (p = 0.007). In conclusion, this study provided evidence of a functional link between coronary blood flow in diseased and nondiseased arteries. Relief of a significant stenosis using PCI globally improved regional and global myocardial blood flow at rest in patients with stable angina. Flow improvement was not apparent at the time of revascularization, but at 6 months' follow-up. Late upturn of the microcirculation may account for delayed recovery of myocardial perfusion