Pancreatic islet beta-cells secrete the hormones insulin, amylin and pancreastatin. To search for further beta-cell hormones, we purified peptides from secretory granules isolated from cultured murine beta TC6-F7 beta-cells. We identified a 34-amino-acid peptide (3948 Da), corresponding to Asp(69)-Leu(102) of the proinsulin-like growth factor II E-peptide, which we have termed 'preptin'. Preptin, is present in islet beta-cells and undergoes glucose-mediated co-secretion with insulin. Synthetic preptin increases insulin secretion from glucose-stimulated beta TC6-F7 cells in a concentration-dependent and saturable manner. Preptin infusion into the isolated, perfused rat pancreas increases the second phase of glucose-mediated insulin secretion by 30%, while anti-preptin immunoglobulin infusion decreases the first and second phases of insulin secretion by 29 and 26% respectively. These findings suggest that preptin is a physiological amplifier of glucose-mediated insulin secretion.
Buchanan et al. Biochem J. 2001 December 1; 360(Pt 2): 431–439.
Buchanan et al. Biochem J. 2001 December 1; 360(Pt 2): 431–439.
Several hormones that regulate nutritional status also impact on bone metabolism.
Preptin is a recently isolated 34-amino acid peptide hormone that is cosecreted
with insulin and amylin from the pancreatic beta-cells. Preptin corresponds
to Asp(69)-Leu(102) of pro-IGF-II. Increased circulating levels of a pro-IGF-II
peptide complexed with IGF-binding protein-2 have been implicated in the high
bone mass phenotype observed in patients with chronic hepatitis C infection.
We have assessed preptin's activities on bone. Preptin dose-dependently stimulated
the proliferation (cell number and DNA synthesis) of primary fetal rat osteoblasts
and osteoblast-like cell lines at periphysiological concentrations (>10(-11)
M). In addition, thymidine incorporation was stimulated in murine neonatal
calvarial organ culture, likely reflecting the proliferation of cells from
the osteoblast lineage. Preptin did not affect bone resorption in this model.
Preptin induced phosphorylation of p42/p44 MAP kinases in osteoblastic cells
in a dose-dependent manner (10(-8)-10(-10) M), and its proliferative effects
on primary osteoblasts were blocked by MAP kinase kinase inhibitors. Preptin
also reduced osteoblast apoptosis induced by serum deprivation, reducing the
number of apoptotic cells by >20%. In vivo administration of preptin increased
bone area and mineralizing surface in adult mice. These data demonstrate that
preptin, which is cosecreted from the pancreatic beta-cell with amylin and
insulin, is anabolic to bone and may contribute to the preservation of bone
mass observed in hyperinsulinemic states such as obesity.
Cornish et al. Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E117-22.
