Josef V. Silha

Perturbations in bone formation and resorption in insulin-like growth factor binding protein-3 transgenic mice.

IGF‐I and their binding proteins are important in bone health. Examination of BMD, osteoblast proliferation, and markers of bone resorption in transgenic mice that constitutively overexpress IGFBP‐3 indicates that overexpression of IGFBP‐3 increases osteoclast number and bone resorption, impairs osteoblast proliferation, and has a significant negative effect on bone formation.

The effects of GH replacement in adult GH‐deficient patients: changes in body composition without concomitant changes in the adipokines and insulin resistance

background  Growth hormone deficiency (GHD) in adult life has been associated with increased central adiposity, decreased insulin sensitivity, dyslipidaemia and increased risk of cardiovascular disease. The effects of GH replacement on adiponectin and resistin, adipokines which have a role in modulating insulin sensitivity have not been previously reported.

Perturbations in adiponectin, leptin and resistin levels in acromegaly: lack of correlation with insulin resistance

background Insulin resistance, impaired glucose tolerance and type 2 diabetes are common in acromegalic subjects. The mechanism underlying this insulin resistance is unclear.

Adipokine levels in Cushing's syndrome; elevated resistin levels in female patients with Cushing's syndrome

background  Cushings syndrome (CS) is associated with central adiposity, insulin resistance and impaired glucose homeostasis. Adipose tissue is thought to regulates glucose homeostasis via circulating adipokines, such as resistin, leptin and adiponectin, although their role in the insulin resistance associated with CS has not been established.

Plasma adipokines and body composition in response to modest dietary manipulations in the mouse.

Objective: The relationship between adipokine levels and body composition has not been carefully examined. Most studies in humans are cross‐sectional, and the few studies in mice have been restricted to a comparison of control animals with markedly obese, insulin‐resistant mice. Our objective was to study changes in adipokine levels and body composition in response to modest dietary intervention.

The effects of growth hormone status on circulating levels of vascular growth factors

Background  Vascular growth factors are important not only in angiogenesis but also for the maintenance of normal endothelial integrity and function. Elevated levels of vascular endothelial growth factor (VEGF), angiopoietin‐2, hepatocyte growth factor (HGF), endostatin and angiogenin have been associated with endothelial dysfunction and atherosclerosis. Both acromegaly and growth hormone deficiency (GHD) are associated with endothelial dysfunction and changes in blood vessel morphology.

Insulin-like Growth Factor Binding Proteins in Development

IGFBPs regulate growth and development by regulating IGF transport to tissues and IGF bioavailability to IGF receptors at cell membrane level. IGFBP excess leads predominantly to inhibition of IGF action and growth retardation with impaired organogenesis. Absence of human and also mouse ALS leads to decreased IGF-I levels in circulation and causes mild growth retardation. Although IGFBP KO mice demonstrate relatively minor phenotypes, the possibility of compensatory mechanisms that mask the phenotypic manifestation of lack of individual binding proteins needs to be further investigated. Recent studies of hepatic regeneration in IGFBP-1 KO mice and also with mutant IGFBP-3 Tg mice provide some limited support for the existence of IGF-independent mechanism of action in vivo.