Chronic hyperglycemia impairs insulin secretion by affecting insulin receptor expression, splicing, and signaling in RIN beta cell line and human islets of Langerhans.

Recent evidence suggests that insulin signaling through the insulin receptor A type (Ex11-), regulates insulin gene transcription. Because chronic hyperglycemia negatively affects insulin receptor function and regulates alternative splicing of the insulin receptor, we inquired whether chronic exposure of pancreatic beta-cells to high glucose results in alterations in insulin signaling due to changes in insulin receptor expression and relative abundance of its spliced isoforms. Our results demonstrate that the insulin receptor is localized in insulin secretory vescicles in human pancreatic beta-cells.

Endothelial nitric oxide synthase polymorphisms are associated with type 2 diabetes and the insulin resistance syndrome.

Endothelial nitric oxide synthase (eNOS) variants were previously demonstrated in cardiovascular disease. To evaluate whether eNOS gene variants are associated with insulin resistance and type 2 diabetes, we evaluated polymorphisms in Exon7 (E298D), intron 18 (IVS18 + 27A-->C), and intron 23 (IVS23 + 10G-->T) in 159 type 2 diabetic patients without macrovascular complications and in 207 healthy control subjects. Samples for all hormonal and metabolic variables were obtained after an overnight fast.

Acute intravenous L-arginine infusion decreases endothelin-1 levels and improves endothelial function in patients with angina pectoris and normal coronary arteriograms: correlation with asymmetric dimethylarginine levels.

Background: We tested the hypothesis that asymmetric dimethylarginine (ADMA) levels could be elevated and influence endothelin-1 and nitric oxide release and action in patients with cardiac syndrome X (CSX). In addition, we evaluated whether an intravenous infusion of L-arginine would improve endothelial function in these subjects.

Methods And Results: Nine patients with CSX and 14 control subjects underwent a continuous infusion of L-arginine (0.

Antitumorigenic and antiinsulinogenic effects of calcitriol on insulinoma cells and solid beta-cell tumors.

Malignant insulinoma is a rare form of cancer with a poor prognosis because of metastatic dissemination and untreatable hypoglycemia. Effective chemotherapy of patients who are not cured by surgery is needed. Calcitriol has known anticancer properties on different neoplastic cell lines, but no data are available regarding its activity on tumorigenic pancreatic beta-cells.

Magnetic resonance image (MRI) of an acquired aorto-pulmonary fistula, associated with cerebral and paradoxical embolism.

Aorto-pulmonary fistula has been described in Marfan's syndrome, with severe degeneration of connective tissue, particularly severe at the aortic site. Rarely, the chronic evolution of this condition could determine the formation of a fistula between the aorta and the adjacent anatomic structures [Ann Thorac Surg 59 (1995) 1563; J Cardiovasc Surg 29 (1988) 403; Thorax 28 (1973) 521]. Here, we describe the first case of aorto-pulmonary fistula, with cerebral and paradoxical embolism, described with angio-nuclear magnetic resonance (MRI) of the heart.

Acute effects of heparin administration on the ischemic threshold of patients with coronary artery disease: evaluation of the protective role of the metabolic modulator trimetazidine.

Objectives: We sought to assess the effects of heparin and the potential protective effects of trimetazidine (TMZ) on exercise performance, plasma nitric oxide (NO), endothelin-1 (ET-1) and free fatty acid (FFA) release in patients with stable coronary artery disease (CAD).

Background: Heparin has been shown to reduce the ischemic threshold in patients with CAD. Trimetazidine may affect myocardial substrate utilization by shifting energy production from FFA to glucose oxidation.