The hormonal peptide Elabela guides angioblasts to the midline during vasculogenesis

A key step in the de novo formation of the embryonic vasculature is the migration of endothelial precursors, the angioblasts, to the position of the future vessels. To form the first axial vessels, angioblasts migrate towards the midline and coalesce underneath the notochord. Vascular endothelial growth factor has been proposed to serve as a chemoattractant for the angioblasts and to regulate this medial migration. Here we challenge this model and instead demonstrate that angioblasts rely on their intrinsic expression of Apelin receptors (Aplr, APJ) for their migration to the midline. We further show that during this angioblast migration Apelin receptor signaling is mainly triggered by the recently discovered ligand Elabela (Ela). As neither of the ligands Ela or Apelin (Apln) nor their receptors have previously been implicated in regulating angioblast migration, we hereby provide a novel mechanism for regulating vasculogenesis, with direct relevance to physiological and pathological angiogenesis.

Parathyroid hormone: past and present

Research on parathyroid hormone (PTH) has undergone four rather distinctive phases, beginning just before the turn of the 20th century. Early debates about the function of the parathyroids were resolved by 1925, when understanding the role of PTH led to comprehending the action of the glands in calcium physiology. Elucidation of the pathophysiology of hormone excess (severe bone loss) and deficiency (hypocalcemia) continued over the following decades. With the advent of advances in chemical and molecular biology, the structure of PTH and its principal receptor (PTHrP-receptor [PTHR1]) were established. Tests with purified hormonal peptide in humans led to the surprising, even paradoxical, finding that PTH can be used pharmacologically to build bone, providing a dramatic therapeutic impact on osteoporosis. These developments have stimulated the field of calcium and bone biology and posed new questions about the role of PTH as well as possible new directions in therapy.

Effect of Glucose on Production and Release of Proinsulin Conversion Products by Cultured Human Islets1

Isolated human islets were examined for the rates of conversion and release of newly formed (pro)insulin-like peptides. The rate of proinsulin (PI) conversion was 2-fold slower in human β-cells (t1/2 = 50 min) than in rat β-cells (t1/2 = 25 min). During the first hour following labeling of newly synthesized proteins, PI represented the main newly formed hormonal peptide in the medium; its release was stimulated 2-fold over the basal level by 20 mmol/L glucose. During the second hour, newly synthesized hormone was mainly released as insulin, with 10- to 20-fold higher rates at 20 mmol/L glucose. Prolonged preculture of the islets at 20 mmol/L glucose did not delay PI conversion, but markedly increased the release of newly formed PI, des31,32-PI, and insulin at both low and high glucose levels. Our data demonstrate that 1) the release of PI provides an extracellular index for the hormone biosynthetic activity of human β-cells; 2) an acute rise in glucose exerts a stronger amplification of the release of converted hormone than in that of nonconverted hormone; and 3) prolonged exposure to high glucose levels results in an elevated basal release of converted and nonconverted PI; this elevation is not associated with a delay in PI conversion, but is attributed to the hyperactivated state of the human β-cell population, which was recently found to be responsible for an elevation in basal rates of hormone synthesis. These in vitro observations on human β-cells provide a possible explanation for the altered circulating (pro)insulin levels measured in nondiabetic and noninsulin-dependent diabetic subjects.

Distribution and postprandial release of porcine peptide YY

ABSTRACT Peptide YY (PYY), a thirty-six amino acid intestinal hormonal peptide with a tyrosine residue at each end (hence YY as Y represents tyrosine in the new peptide nomenclature), was found throughout the gastrointestinal tract of the pig. Concentrations were very low in the foregut (antrum, 3·4 ± 0·3 pmol/g; duodenum, 1·1 ± 1·5 pmol/g), higher in the distal small intestine (ileum, 100 ± 13 pmol/g) and very high in the large bowel (descending colon, 270 ± 45 pmol/g). Peptide YY was found to circulate in plasma and concentrations rose substantially in response to eating (fasting, 138 ± 15 pmol/l; postprandial, 263 ± 21 pmol/l; P<0·001). There was a small but significant portal/arterial gradient in postprandial PYY levels. More than 90% of the immunoreactive PYY in gut extracts eluted, on gel permeation chromatography, in an identical position to pure PYY standard, but small amounts of higher molecular weight material, possibly precursors, were detected. In contrast, plasma from fasting pigs contained a large proportion (60–70%) of these large molecular forms. These findings suggest that the putative pro-PYY may be cleared more slowly from the circulation than the 36 amino acid hormonal peptide. The high concentrations of immunoreactive PYY in the circulation of the young pig may reflect a species difference between pig and man or may indicate an important role for PYY in the developing animal. J. Endocr. (1987) 113, 11–14