Endocrine Abstracts

Bone marrow mesenchymal stem cells (MSCs) have been shown to differentiate into various lineages in vivo and in vitro. Recent reports have shown that adult mouse bone marrow can differentiate toward a pancreatic endocrine beta-cells phenotype; Once engrafted into the host, bone marrow-derived cells exhibit markers and physiological behavior characteristic of pancreatic beta-cells, thus providing a new methods for the therapy and treatment of diabetes. In this study, we explore...

Transdifferentiation of non-endocrine pancreatic cells towards a beta-cell phenotype may enable insulin independence in many individuals from a single donor. This will be dependent on near-physiological proinsulin biosynthesis, processing, storage and secretion. The aim of this study was to fully characterise endocrine potential of pancreatic acinar cells before and after transdifferentiation.Expression of exocrine/endocrine markers in the AR42J rat acin...

We have previously used insulin-secreting MIN6 cells configured into islet-like structures (pseudoislets) to demonstrate that homotypic interactions between beta-cells are essential for normal insulin secretory responses. We have now investigated whether homotypic interactions are important in secretion of other pancreatic hormones. Glucagon-secreting alpha-TC1 cells were cultured as adherent monolayers, or as pseudoislets grown on gelatin, and hormone release was measured in ...

The insulin-like growth factor binding proteins (IGFBPs-1 to -6) complex IGF-I and -II and were originally assumed to limit IGF access to the main IGF signalling receptor (IGFR) and decrease IGF activity. IGFBP-5 is the most conserved of the IGFBPs. Examination of its primary sequence reveals that, in addition to the key IGF binding domain, additional functional motifs are present that are not related to its IGF binding function.IGFBP-5 is upregulated du...

Recent investigations into the pathogenesis of Kallmann's syndrome (KS) have pointed to the importance of anosmin-1 and FGFR1 (fibroblast growth factor receptor-1), the gene products for the X-linked and an autosomal dominant form of KS respectively, in olfactory, GnRH-1 neuronal systems and kidney ontogeny. Disturbed anosmin-1/FGFR1 pathways lead to partial or complete failure of OB (olfactory bulb) development and arrest of GnRH-1 neuronal migration, explaining the predomina...

Mouse distal Chromosome 2 has a proximal region containing a single imprinted gene, Neuronatin, Nnat. In situ hybridisation has shown strong expression of neuronatin in the embryonic mouse Rathke's pouch and primordial anterior pituitary (Wijnholds et al 1995, Dev Biol 171:73-84) and has been proposed to participate in pituitary development. Uniparental maternal inheritance of the proximal region leads to decreased folding of the cerebellum (Kikyo et al 1997, Dev Biol 190:66-7...

Our recent studies show that perinatal exposure to the synthetic glucocorticoid (GC), dexamethasone, altered the number of dopaminergic cell bodies in mesencephalic nuclei in adult male and female rats, with implications for mood, behaviour and motor activity. The present study therefore aimed to determine whether hypothalamic dopaminergic populations are also subject to such 'programming' effects. Using timed pregnant rats, dexamethasone was included in the drinking water bet...

BACKGROUND Human and animal evidence indicates that poor maternal nutrition leads to programmed endothelial dysfunction and hypertension in offspring. In humans, endothelial dysfunction has been observed in independent cohorts studied aged 7 and 11, but explanatory molecular mechanisms are lacking. Endothelial function, and synthesis of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS), relies on nutrient supply of L-arginine, with maternal dietary restriction in r...