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Biomedical subjects

Jacob Ilany

Publications and source records attributed to Jacob Ilany.

6 recordsLinked to original sources

Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level.

Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes.

Amino Acids↗

Feedback inhibition of gonadotropins by testosterone in men with hypogonadotropic hypogonadism: comparison to the intact pituitary-testicular axis in primary hypogonadism.

Men with hypogonadotropic hypogonadism (HH) due to hypothalamic-pituitary disease present with low serum testosterone levels combined with undetectable, low, or normal gonadotropin levels. Treatment consists of testosterone replacement to reverse the symptoms of androgen deficiency. The aim of this study was to examine the dynamics and feedback inhibition of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in relation to testosterone in 38 men with HH treated with testosterone. Findings were compared with 11 men with primary hypergonadism (PH). Testosterone replacement led to a suppression of FSH levels from 2.8 IU/L at baseline to 1.1 IU/L and to a suppression of LH levels from 2.3 to 0.8 IU/L. There was a linear correlation between levels of FSH and LH (after natural log transformation for both) and testosterone levels in both the HH and PH groups. However, the differences in intercepts and slopes between the groups were significant. To determine whether nonsuppressed FSH or LH during testosterone replacement reduces the probability of eugonadism, as reflected by normal testosterone levels, gonadotropin levels were measured and categorized as low (<0.5 IU/L), medium (0.5-2 IU/L), and high levels (>2 IU/L). The higher FSH or LH levels were found to significantly decrease the chance for achieving eugonadism. In conclusion, in men with HH due to hypothalamic-pituitary disease or injury, the pituitary-testicular hormonal axis maintains its physiological negative feedback between testosterone and gonadotropins. Thus, gonadotropin levels in men with HH might be useful, together with testosterone concentrations, for assessing the adequacy of androgen replacement.

Adolescent↗

Scanning electron microscopy of thyroid cells under fully hydrated conditions--a novel technique for a seasoned procedure: a brief observation.

Technical information for handling fine-needle aspiration samples from thyroid lesions for WETSEM electron microscopy is presented. The use of wet SEM technology maintains cytological features of the thyroid cells, in the atmospheric electronic microscope chamber without the need for solidification. Images are presented from normal and pathological thyroid specimens showing subcellular elements unavailable to the cytopathologist by light microscopy. Of 24 samples, 18 were adequate for clinical evaluation. In 16 of these 18 specimens, we could find features compatible with the final histological or cytological diagnosis (post-hoc). In two cases, the cell features were too unique to be interpretable. Because this procedure is relatively simple, there is potential for the use of this technology as an adjunct to light microscopy in clinical and research settings.

Adult↗

Low-dose recombinant human thyrotropin-aided radioiodine treatment of large, multinodular goiters in elderly patients.

OBJECTIVE: We aimed to assess low-dose recombinant human thyroid-stimulating hormone (rhTSH)-aided, fixed-activity radioiodine therapy of large, multinodular goiters (MNGs) in elderly patients with comorbidities. DESIGN: This was a short-term, observational study. METHODS: We measured 24-h thyroid radioiodine uptake (RAIU) of 2 microCi 131-iodine at baseline and 24 h after intramuscular injection of 0.03 mg rhTSH in 17 patients (aged 60-86 years, 12 women), who subsequently received 30 mCi 131-iodine 24 h after an identical rhTSH injection. TSH and free thyroxine (FT4) were measured at baseline and days 10, 30 and 90 after therapy. Thyroid volume was assessed by computed tomography at baseline and day 180. RESULTS: rhTSH, 0.03 mg, significantly increased mean 24-h thyroid RAIU from 25.8% +/- 10.3% to 43.3% +/- 8.4% (68% relative increase; t(16) = -8.43, P < 0.001). The proportion of patients overtly or subclinically hyperthyroid (TSH < 0.5 mU/l) decreased from 71% (12/17) at baseline to 19% (3/16) at 3 months. Mean serum FT4 peaked at slightly above normal range, 25.9 +/- 7.7 pmol/l (46% over baseline) and was 21% under baseline levels at 3 months. Mean estimated thyroid volume fell 34% from baseline to 6 months (170.0 +/- 112.8 to 113.1 +/- 97.5 ml; P < 0.01). Symptomatic relief, improved well-being, and/or reduction or elimination of antihyperthyroid medication were seen in 76% of patients. Three (18%) patients had transient neck pain or tenderness, or palpitations; one had transient asymptomatic thyroid enlargement; and three (18%) became hypothyroid by 3 months. CONCLUSIONS: Intramuscular rhTSH, 0.03 mg, followed 24 h later by 30 mCi 131-iodine, is a safe, effective and convenient treatment for MNG in elderly patients with comorbidities.

Aged↗

The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance.

Insulin receptors (IRs) on vascular endothelial cells have been suggested to participate in insulin-regulated glucose homeostasis. To directly address the role of insulin action in endothelial function, we have generated a vascular endothelial cell IR knockout (VENIRKO) mouse using the Cre-loxP system. Cultured endothelium of VENIRKO mice exhibited complete rearrangement of the IR gene and a more than 95% decrease in IR mRNA. VENIRKO mice were born at the expected Mendelian ratio, grew normally, were fertile, and exhibited normal patterns of vasculature in the retina and other tissues. Glucose homeostasis under basal condition was comparable in VENIRKO mice. Both eNOS and endothelin-1 mRNA levels, however, were reduced by approximately 30-60% in endothelial cells, aorta, and heart, while vascular EGF expression was maintained at normal levels. Arterial pressure tended to be lower in VENIRKO mice on both low- and high-salt diets, and on a low-salt diet VENIRKO mice showed insulin resistance. Thus, inactivation of the IR on endothelial cell has no major consequences on vascular development or glucose homeostasis under basal conditions, but alters expression of vasoactive mediators and may play a role in maintaining vascular tone and regulation of insulin sensitivity to dietary salt intake.

Animals↗