Papotti, M.

Unacylated ghrelin and obestatin increase islet cell mass and prevent diabetes in streptozotocin-treated newborn rats (Article)

2010-07-01T00:00:00Z

The ghrelin gene products, namely acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (Ob), were shown to prevent pancreatic β-cell death and to improve β-cell function under treatment with cytokines, which are major cause of β-cell destruction in diabetes. Moreover, AG had been described previously to prevent streptozotocin (STZ)-induced diabetes in rats; however, the effect of either UAG or Ob has never been examined in this context. In the present study, we investigated the potential of UAG and Ob to increase islet β-cell mass and to reduce diabetes at adult age in STZ-treated neonatal rats. One-day-old rats were injected with STZ and subsequently administered with either AG, UAG or Ob for 7 days. On day 70, plasma glucose levels, plasma and pancreatic insulin levels, pancreatic islet area and number, insulin and pancreatic/duodenal homeobox-1 (Pdx1) gene expression, and antiapoptotic BCL2 protein expression were determined. Similarly to AG, both UAG and Ob counteracted STZ-induced high glucose levels and improved plasma and pancreatic insulin levels, which were reduced by the diabetogenic compound. UAG and Ob increased islet area, islet number, and β-cell mass with respect to STZ treatment alone. Finally, in STZ-treated animals, UAG and Ob up-regulated insulin and Pdx1 mRNA and increased the expression of BCL2 similarly to AG. Taken together, our results suggest that in STZ-treated newborn rats, UAG and Ob improve glucose metabolism and preserve islet cell mass, granting a therapeutic potential in medical conditions associated with impaired β-cell function.

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Follow-up and documentation (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Chemotherapy in patients with neuroendocrine tumors (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Radiological examinations (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Biochemical markers (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Towards a standardized approach to the diagnosis of gastroenteropancreatic neuroendocrine tumors and their prognostic stratification (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Pre- and perioperative therapy in patients with neuroendocrine tumors (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Echocardiography (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Peptide receptor radionuclide therapy with radiolabeled somatostatin analogs (Article)

2009-08-01T00:00:00Z

The purpose of this guideline is to assist physicians caring for patients with neuroendocrine tumors in considering eligibility criteria for peptide receptor radionuclide therapy (PRRT), and in defining the minimum requirements for PRRT. This guideline also makes recommendations on what minimal patient, tumor, and treatment outcome characteristics should be reported for PRRT in order to make comparisons between studies possible. It is not this guideline's aim to give specific recommendations on the use of specific radiolabeled somatostatin analogs for PRRT because different analogs are being used, and their availability depends on national law and local permissions.

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Biotherapy (Article)

2009-08-01T00:00:00Z

ENETS consensus guidelines for the standards of care in neuroendocrine tumors: Somatostatin receptor imaging with IIIIn-pentetreotide (Article)

2009-08-01T00:00:00Z

Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. (Article)

2004-06-01T00:00:00Z

Ghrelin possesses strong GH-releasing activity but also other endocrine activities including stimulation of PRL and ACTH secretion, modulation of insulin secretion and glucose metabolism. It is assumed that the GH secretagogue (GHS) receptor (GHS-R) 1a mediates ghrelin actins provided its acylation in Serine 3; in fact, acylated ghrelin only is able to exert endocrine activities. Acylated ghrelin (AG) is present in serum at a 2.5 fold lower concentration than unacylated ghrelin (UAG). UAG, however, is not biologically inactive; it shares with AG some non-endocrine actions like cardiovascular effects, modulation of cell proliferation and even some influence on adipogenesis. Thus, these actions are likely to be mediated by GHS-R subtypes able to bind ghrelin independently of its acylation. In order to further clarify whether UAG is really devoid of any endocrine action, we studied the interaction of the combined administration of AG and UAG (1.0 microg/kg i.v.) in 6 normal young volunteers (age [mean +/- SE]: 25.4 +/- 1.2 yr; BMI: 22.3 +/- 1.0 kg/m2). As expected, AG induced marked increase (p < 0.01) in circulating GH, PRL, ACTH and cortisol levels. AG administration was also followed by a decrease in insulin levels (-285.4 +/- 64.8 mU*min/l; p < 0.05) and an increase in plasma glucose levels (1068.4 +/- 390.4 mg*min/dl; p < 0.01). UAG alone did not induce any change in these parameters. UAG also failed to modify the GH, PRL, ACTH and cortisol responses to AG. However, when UAG was co-administered together with AG, no significant change in insulin (-0.5 +/- 40.9 mU*min/l) and glucose levels (455.9 +/- 88.3 mg*min/dl) was recorded anymore, indicating that the insulin and glucose response to AG has been abolished by UAG. In conclusion, non-acylated ghrelin does not affect the GH, PRL, and ACTH response to acylated ghrelin but is able to antagonize the effects of acylated ghrelin on insulin secretion and glucose levels. These findings indicate that unacylated ghrelin is metabolically active and is likely to counterbalance the influence of acylated ghrelin on insulin secretion and glucose metabolism. As GHS-R1a is not bound by unacylated ghrelin, these findings suggest that GHS receptor subtypes mediate the metabolic actions of both acylated and unacylated ghrelin.