Endocrine Abstracts

Preadipocytes differentiate into mature adipocytes when treated with insulin, T3, isobutylmethylxanthine and dexamethasone but the role of their autocrine factors in their survival and function has only recently been appreciated. We have examined the expression and role of autocrine FGF-2 during preadipocyte differentiation. Using human preadipocytes isolated from subcutaneous fat, we induced differentiation in differentiation medium with and without the insulin-sensitising dr...

Adiponectin is an adipocyte derived-hormone, associated with insulin sensitivity and a lower risk of atherosclerosis. As central rather than gluteo-femoral fat is known to increase the risk of type 2 diabetes (T2DM) and cardiovascular disease we investigated the mRNA and protein expression of adiponectin in human adipose tissue depots. RNA and protein was extracted using a cohort of 46 human adipose tissue samples (non-diabetic (ND) (age: (mean plus/minus SD) 44.33 plus/minus ...

Resistin is a newly-described hormone whose expression in adipose tissue is regulated by fasting, insulin and obesity. We recently reported that resistin mRNA is also expressed in mouse hypothalamus and pituitary (FEBS Letts. 526, p26 (2002)). In the present study we hypothesized that adiposity would influence hypothalamic resistin immunoreactivity (ir). Two different, polyclonal antisera ( raised against aa 51-108, human ; aa 83-91, mouse ) revealed resistin ir in coronal sec...

BACKGROUND: The reason for reduction in appetite following gastro intestinal bypass procedures in man and in animal models remains unclear. Rats following jejunum intestinal bypass eat significantly less compared to sham operated rats and this seem due to a transferable factor in plasma. Such a humoral factor may be a therapeutic option for obesity. PYY, produced from the distal small bowel and colon is elevated in man and rodents following small bowel resection and ilial bypa...

Metabolism of glucocorticoids to dihydro and tetrahydro derivatives via hepatic 5alpha- and 5beta-reductases has been assumed to be a pathway of irreversible inactivation of glucocorticoids. However, 5alpha-reduced metabolites of other steroids (testosterone, aldosterone) have significant affinity for the parent hormone receptor. We have investigated whether 5alpha-reduced metabolites of corticosterone (B) are GR agonists.In hepatocytes from male lean Zucker rats (n=6) com...

11beta-Hydroxysteroid dehydrogenase (11beta-HSD) catalyses the interconversion of hormonally active cortisol (F) and inactive cortisone (E). 11beta-HSD1 is an NADP(H) dependent enzyme expressed in human liver and adipose that is targeted to the ER membrane with a lumenal catalytic domain. In vivo the enzyme acts predominantly as a reductase, generating F from E. The inherited condition, Apparent Cortisone Reductase Deficiency (ACRD) is a form of PCOS characterised by ACTH medi...

The global epidemic of obesity has heightened the need to understand the mechanisms that underpin its pathogenesis. Clinical observations in patients with Cushing's syndrome have highlighted the link between cortisol and central obesity. However, whilst circulating cortisol levels are normal or reduced in obesity, local regeneration of cortisol, from inactive cortisone, by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has been postulated as a pathogenic mechanism. W...

11HSD1 regenerates cortisol from cortisone and maintains glucocorticoid receptor (GR) activation. Adipose-specific transgenic 11HSD1 overexpression in mice causes obesity, insulin resistance, and hypertension (reflecting increased adipose angiotensinogen); however, the effect depended upon local GR expression. In human obesity, 11HSD1 activity is increased similarly in biopsied adipose, but the impact remains uncertain. We tested whether increased adipose 11HSD1 activity in ob...