[Cardiomyopathy induced by frequent premature ventricular complexes originating from the right ventricular outflow tract: left ventricular systolic function recovery after transcatheter ablation].

Left ventricular dysfunction due to frequent isolated premature ventricular complexes originating from the right ventricular outflow tract (RVOT) in patients without structural heart disease and in the absence of sustained ventricular tachycardia is a rare and poorly characterized entity. Successful identification and radiofrequency catheter ablation of the focal source of ventricular ectopy is the most effective treatment for these patients, leading to a complete normalization of ventricular dimensions and contractile function. In this article, we report two cases of left ventricular dysfunction resulting from frequent isolated premature ventricular complexes originating from the RVOT.

High insulin levels impair intracellular receptor trafficking in human cultured myoblasts.

Chronic hyperinsulinemia is both a marker and a cause for insulin resistance. This study analyzes the effect of long-term exposure to high insulin levels on insulin-insulin receptor metabolism in human myoblasts. Cells were grown in the presence of low (107 pM, SkMC-L) or high (1430 pM, SkMC-H) insulin concentrations.

Uptake of amiodarone by thyroidal and non-thyroidal cell lines.

Amiodarone perturbs thyroid function, causing overt hypothyroidism or hyperthyroidism in 15% of patients. Changes in thyroid function are likely due, at least in part, to amiodarone and/or desethylamiodarone (DEA) concentration into the thyroid gland, but mechanisms whereby the drug uptake occurred are not known. Thyroidal (FRTL-5) or non-thyroidal [Chinese hamster ovary wild-type (CHOwt) or CHO stably transfected with NIS (CHO-NIS)] cells were exposed to 10 microM amiodarone or DEA.

Continually high insulin levels impair Akt phosphorylation and glucose transport in human myoblasts.

Chronic hyperinsulinemia is both a marker and a cause for insulin resistance. This study analyzes the effect of long-term exposure to high insulin levels on the insulin-signaling pathway and glucose transport in cultured human myoblasts. Human myoblasts were grown in the presence of low (107 pmol/L, SkMC-L) or high (1430 pmol/L, SkMC-H) insulin concentrations for 3 weeks.

The extracellular portion of the insulin receptor beta-subunit regulates the cellular trafficking of the insulin-insulin receptor complex. Studies on Chinese hamster ovary cells carrying the Cys 860-->Ser insulin receptor mutation.

Objective: Chinese hamster ovary (CHO) cells transfected with human engineered insulin receptor (IR) cDNA to mutate Cys 860 to Ser (CHO-IR(C860S)) showed a defective insulin internalization without affecting insulin binding and IR autophosphorylation. Moreover, this mutation reduces insulin receptor substrate (IRS)-1 tyrosine phosphorylation and insulin-induced metabolic and mitogenic effects. Altogether, these observations support a role of the extracellular domain of IR beta-subunit in insulin and receptor intracellular targeting as well as in insulin signaling.

Insulin permeability across an in vitro dynamic model of endothelium.

Purpose: Endothelium insulin permeability was investigated using in vitro, dynamic culture of endothelial cells.

Methods: Endothelial cells were cultured in a hollow fiber apparatus and continuously exposed to a flow. Transendothelial electrical resistance and permeability to [14C]sucrose and [14C]inulin were used to monitor the integrity of the endothelial monolayer.

Obesity modulates the expression of haptoglobin in the white adipose tissue via TNFalpha.

Increase in adipose mass results in obesity and modulation of several factors in white adipose tissue (WAT). Two important examples are tumor necrosis factor alpha (TNFalpha) and leptin, both of which are upregulated in adipose tissue in obesity. In order to isolate genes differentially expressed in the WAT of genetically obese db/db mice compared to their lean littermates, we performed RNA fingerprinting and identified haptoglobin (Hp), which is significantly upregulated in the obese animals.

Agonist-induced internalization and recycling of the human A(3) adenosine receptors: role in receptor desensitization and resensitization.

A(3) adenosine receptors have been proposed to play an important role in the pathophysiology of cerebral ischemia with a regimen-dependent nature of the therapeutic effects probably related to receptor desensitization and down-regulation. Here we studied the agonist-induced internalization of human A(3) adenosine receptors in transfected Chinese hamster ovary cells, and then we evaluated the relationship between internalization and signal desensitization and resensitization. Binding of N(6)-(4-amino-3-[(125)I]iodobenzyl)adenosine-5'-N-methyluronamide to membranes from Chinese hamster ovary cells stably transfected with the human A(3) adenosine receptor showed a profile typical of these receptors in other cell lines (K:(D) = 1.

Intracellular hyperinsulinism: a metabolic characteristic of obesity with and without Type 2 diabetes: intracellular insulin in obesity and Type 2 diabetes.

There is evidence that intracellular insulin may carry out some insulin mediated actions, including glucose transport. As intracellular insulin has never been quantitatively assessed in human cells, we evaluated its concentrations in monocytes from normal subjects (n = 7) and obese patients without (n = 9) and with Type 2 diabetes mellitus (n = 10). After the incubation of cells with labeled insulin for 60 min at 37 degrees C, intracellular intact insulin concentrations were measured by HPLC and expressed as pmol x 10(-6).

Plasma leptin levels in newborns from normal and diabetic mothers.

Leptin can be considered as a peripheral signal which informs the centers about the mass of energy stores. Studies done on the human adult population have demonstrated that degree of adiposity and insulin levels play a major role as determinants of leptin circulating levels. The aim of this study was to evaluate which factors may influence leptin levels at birth.

Inhibition of endosomal acidification in normal cells mimics the derangements of cellular insulin and insulin-receptor metabolism observed in non-insulin-dependent diabetes mellitus.

Dissociation of the insulin-insulin receptor complex plays a crucial role in the processing of both insulin and the insulin receptor, and the acidification of endocytic vesicles may be the mechanism by which internalized insulin is dissociated from its receptor and properly sorted and processed. Internalized insulin-insulin receptor complexes are abnormally processed in cells from patients with non-insulin-dependent diabetes mellitus (NIDDM). Accordingly, to further investigate the mechanisms of the derangements observed in NIDDM cells, we examined the effects of the ionophore monensin, which inhibits endosomal acidification, on the cellular processing of insulin and insulin receptor in monocytes from control subjects (n = 12) and NIDDM patients (n = 14).

Long-term survival and function of isolated bovine pancreatic islets maintained in different culture media.

Bovine islets are being evaluated for their potential in transplantation studies. We studied the recovery, morphology, and function of purified bovine islets cultured up to 4 weeks under varying conditions. Approximately 60% of the initial islet mass could be recovered after 4 weeks at 37 degrees C in CMRL 1066 or M 199 culture medium, and the cultured islets were well preserved histologically and viable both in vitro and in vivo.

A prevalence study of known diabetes mellitus in Tuscany assessed from pharmaceutical prescriptions and other independent sources.

This study evaluates the prevalence of diabetes mellitus (DM) in Pisa (Tuscany, Italy) using four independent data sources. The main source, represented by computerized prescriptions for anti-diabetic agents collected over a 4-month period, was validated using three secondary sources: (a) the list of diabetic patients who receive material of self-care from the National Health Service; (b) the clinical records of diabetic patients obtained from a random sample of family doctors; (c) the clinical records of diabetic patients attending our outpatient clinic. The main source provided 3806 patients, and 697 patients were added from the secondary sources, thus identifying a total number of 4503.

Insulin degradation in vitro and in vivo: a comparative study in men. Evidence that immunoprecipitable, partially rebindable degradation products are released from cells and circulate in blood.

The products of insulin metabolism generated in vitro and in vivo were compared in this study. Monocytes from 10 control subjects were incubated with 125IA14-labeled insulin, acid washed, and solubilized or reincubated in insulin-free binding buffer to study both intracellular radioactivity or radioactivity released from cells to medium. To evaluate in vivo insulin metabolism, labeled insulin (100-120 microCi) was injected as a single intravenous bolus in 5 of the 10 subjects.

Insulin degradation in vivo: a high-performance liquid chromatographic analysis.

The metabolism of insulin in vivo was investigated using an isocratic reversed-phase high-performance liquid chromatographic (RP-HPLC) method. After intravenous injection of A14-[125I]insulin into normals, eight labelled insulin derivatives were found in plasma (peaks 1-8). Two of them (peaks 1 and 7) showed an elution pattern identical with those of reference [125I]monoiodotyrosine and intact A14-[125I]insulin, respectively.

Diurnal pattern of plasma metformin concentrations and its relation to metabolic effects in type 2 (non-insulin-dependent) diabetic patients.

The authors describe the diurnal profile of plasma metformin concentrations in a group of 6 Type 2 (noninsulin-dependent) diabetic patients studied at two different daily metformin doses (500 mg and 850 mg b.d.) and report data on the relationships between plasma metformin and metabolic effects over a 14 h period.

[Efficacy of sulfonylurea and sulfonylurea-benfluorex therapy in patients with type 2 diabetes treated with commercial sulfonylurea-biguanide combinations].

This study tests the possibility to avoid the use of phenformin in 40 type 2 (non insulin dependent) diabetic patients treated with the commercial sulphonylurea-phenformin combinations. In diabetic patients treated with sulphonylureas and phenformin at low dosage (glibenclamide 5 mg and phenformin 50 mg) it was possible to maintain good glycometabolic control using only the sulphonylurea gliclazide (160 mg/die). The diabetic patients on treatment with sulphonylureas and phenformin at higher dosage (glibenclamide 7.

Improvement with metformin in insulin internalization and processing in monocytes from NIDDM patients.

This study investigated the relative effect of obesity alone and in combination with non-insulin-dependent diabetes mellitus (NIDDM) on the intracellular processing of insulin and evaluated the effect of metformin therapy on this process. Monocytes from 11 obese hyperinsulinemic subjects, 13 obese hyperinsulinemic NIDDM patients, and 7 nondiabetic control subjects were incubated with A14-125I-labeled insulin for 60 min at 37 degrees C, and intracellular insulin degradation was characterized by high-performance liquid chromatography. Total cell-associated insulin (insulin binding) and internalized and degraded insulin were decreased in obese subjects and significantly decreased in obese NIDDM patients compared with nondiabetic control subjects.

Ibopamine does not affect insulin resistance in patients with type I diabetes.

Diabetes mellitus was assessed by investigating 8 type I diabetic patients, in good metabolic control and with congestive heart failure, who were studied after 3 weeks of placebo and ibopamine (100 mg t.i.d.

Salivary immunoreactive insulin concentrations are related to plasma free-insulin levels in insulin-treated diabetic patients.

Salivary immunoreactive insulin was measured in 45 insulin-treated diabetic patients directly from saliva samples by a radioimmunoassay procedure. Mean and median fasting salivary immunoreactive insulin was respectively 88.5 and 54.