ATP-sensitive K+ channel mediates the zinc switch-off signal for glucagon response during glucose deprivation.

OBJECTIVE: The intraislet insulin hypothesis proposes that glucagon secretion during hypoglycemia is triggered by a decrease in intraislet insulin secretion. A more recent hypothesis based on in vivo data from hypoglycemic rats is that it is the decrease in zinc cosecreted with insulin from beta-cells, rather than the decrease in insulin itself, that signals glucagon secretion from alpha-cells during hypoglycemia. These studies were designed to determine whether closure of the alpha-cell ATP-sensitive K(+) channel (K(ATP) channel) is the mechanism through which the zinc switch-off signal triggers glucagon secretion during glucose deprivation. RESEARCH DESIGN AND METHODS: All studies were performed using perifused isolated islets. RESULTS: In control experiments, the expected glucagon response to an endogenous insulin switch-off signal during glucose deprivation was observed in wild-type mouse islets. In experiments with streptozotocin-treated wild-type islets, a glucagon response to an exogenous zinc switch-off signal was observed during glucose deprivation. However, this glucagon response to the zinc switch-off signal during glucose deprivation was not seen in the presence of nifedipine, diazoxide, or tolbutamide or if K(ATP) channel knockout mouse islets were used. All islets had intact glucagon responses to epinephrine. CONCLUSIONS: These data demonstrate that closure of K(ATP) channels and consequent opening of calcium channels is the mechanism through which the zinc switch-off signal triggers glucagon secretion during glucose deprivation.

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.

Intrahepatic glucose flux as a mechanism for defective intrahepatic islet alpha-cell response to hypoglycemia.

OBJECTIVE: Glucagon responses to hypoglycemia from islets transplanted in the liver are defective. To determine whether this defect is related to intrahepatic glycogen, islets from inbred Lewis rats were transplanted into the hepatic sinus (H group), peritoneal cavity (P group), omentum (O group), and kidney capsule (K group) of recipient Lewis rats previously rendered diabetic with streptozotocin (STZ). RESEARCH DESIGN AND METHODS: Glucagon responses to hypoglycemia were obtained before and after transplantation under fed conditions and after fasting for 16 h and 48 h to deplete liver glycogen. RESULTS: Glucagon (area under the curve) responses to hypoglycemia in the H group (8,839 +/- 1,988 pg/ml per 90 min) were significantly less than in normal rats (40,777 +/- 8,192; P < 0.01). Fasting significantly decreased hepatic glycogen levels. Glucagon responses in the H group were significantly larger after fasting (fed 8,839 +/- 1,988 vs. 16-h fasting 24,715 +/- 5,210 and 48-h fasting 29,639 +/- 4,550; P < 0.01). Glucagon response in the H group decreased after refeeding (48-h fasting 29,639 +/- 4,550 vs. refed 10,276 +/- 2,750; P < 0.01). There was no difference in glucagon response to hypoglycemia between the H and the normal control group after fasting for 48 h (H 29,639 +/- 4,550 vs. control 37,632 +/- 5,335; P = NS). No intragroup differences were observed in the P, O, and K groups, or normal control and STZ groups, when comparing fed or fasting states. CONCLUSIONS: These data suggest that defective glucagon responses to hypoglycemia by intrahepatic islet alpha-cells is due to dominance of a suppressive signal caused by increased glucose flux and glucose levels within the liver secondary to increased glycogenolysis caused by systemic hypoglycemia.

[Optical coherence tomography]. / Tomografia a coerenza ottica.

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.