Circulating ghrelin levels of visceral obese men are not modified by a short-term treatment with very low doses of GH replacement.

Ghrelin, the endogenous ligand for the GH secretagogue-receptor (GHS-R), in addition to its GH-releasing action, has orexigenic and adipogenic properties. These characteristics make ghrelin a potential hormone involved in the pathogenesis of obesity. Ghrelin levels are decreased in obese humans and it is unknown whether this decrease is responsible for the blunted GH secretion reported in visceral obesity. Since only few data are available on the potential feedback regulation by GH on systemic ghrelin concentrations, it remains to be established whether the correction of circulating GH concentrations in obese individuals affects ghrelin concentrations. To answer this question, we measured plasma ghrelin levels after a week of administration of low doses of recombinant human GH (rhGH) in a randomized, double-blind, placebo (PL)-controlled trial. This study was originally designed to evaluate the effects of GH replacement on lipid kinetics in visceral obese men. Six adult men with abdominal/visceral obesity (age 42+/-3 yr, body weight 107 +/- 10 kg, BMI 33 +/- 1 kg/m2, waist circumference 111 +/- 3 cm, mean +/- SE) were evaluated in the basal state (BS) and after one week of treatment with subcutaneous bedtime injections of either PL, 2.5 (GH2.5) or 3.3 (GH3.3) pg/kg/die of rhGH. In comparison to BS either PL, GH2.5 or GH3.3 did not significantly modify circulating ghrelin concentrations (p = 0.77). In contrast, a significant increase of serum GH (p = 0.0028), IGF-I (p = 0.0033) and whole body rate of lipolysis (p = 0.038, GH2.5; p = 0.009, GH3.3) occurred, in comparison to BS or PL, after GH2.5 and GH3.3, without differences between the two treatments. These data demonstrate that in abdominal/visceral obese men a short-term treatment with very low doses of rhGH replacement, sufficient to augment the rate of lipolysis, do not modify circulating ghrelin levels.

Effects of anti-oxidizing vitamins on in vitro cultured porcine neonatal pancreatic islet cells.

Oxidative stress may cause severe cellular damage to both allo- and xeno-transplanted islets, additional to islet graft-directed immunity, in diabetic patients. We thus aimed to examine the effects of antioxidants on in vitro culture-maintained, neonatal porcine cell clusters (NPCCs). NPCCs were treated with antioxidants (vitamins D3 and E) by a certain time of their maturation and differentiation process. Insulin recovery showed that both vitamins D3 and E, unlike untreated controls, resulted in preservation of the islet function for significantly long periods of time. Such effects were also confirmed during NPCCs in vitro static incubation with high glucose. Furthermore, morphologic examination of NPCCs demonstrated that at 16 days of cell culture beta-cell clusters were significantly larger and more intact when exposed to the vitamins as compared to controls. According to these preliminary results, because the employed vitamins, known to retain anti-oxidizing properties, seemed to clearly improve NPCCs morphology and function, they may represent a potentially useful tool for islet culture maintenance in the pre-transplant time period.

Detection of particulate guanylate cyclase in rat neurohypophysis after stimulation with ANF and BNP: an ultracytochemical study.

We investigated the ultracytochemical localization of particulate guanylate cyclase (GC) in the rat neurohypophysis after activation with rat atrial natriuretic factor (rANF) or porcine brain natriuretic peptide (pBNP). Under our experimental conditions, the presence of GC reaction product indicated that rANF and pBNP were strong activators of particulate GC since samples incubated in basal conditions without rANF or pBNP did not reveal any GC reaction product. The rANF-stimulated GC was localized both to pituicytes and to nerve fibers and endings whereas the pBNP-stimulated GC was present exclusively in nerve fibers and endings. Recently, two subtypes of receptors for natriuretic peptides have been identified as two isoforms of particulate GC [24,50]. Our data indicate that the receptors of the two hormones have a partially distinct distribution in the rat neurohypophysis. In pituicytes, GC reaction product was found on plasma membrane of finger-like processes and on the membranes surrounding the lipid droplets. In nerve fibers and endings, GC reaction product was associated with intracellular membranes. This finding suggests that the enzyme could mediate an internal inhibitory action of these hormones on the release of vasopressin and oxytocin.