Preptin, another peptide product of the pancreatic β-cell, is osteogenic in vitro and in vivo

Abstract

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 ␤-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 (Ͼ10 Ϫ11 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 Ϫ8-10 Ϫ10 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 Ͼ20%. 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 ␤-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.osteoblast; bone-active hormone; bone anabolic THE MAINTENANCE OF THE MECHANICAL INTEGRITY of the skeleton depends on bone remodelling, the well-coordinated balance between bone formation by osteoblasts and bone resorption by osteoclasts. The coupled action of osteoblasts and osteoclasts is regulated by the action of many local and circulating hormones and factors. More recently, leptin-mediated central regulation of bone mass has been demonstrated (14). This appears to be mediated by a neurological rather than an endocrine mechanism (1). If there is uncoupling of the components of bone remodeling, such that bone resorption exceeds bone formation, bone loss occurs, leading to osteoporosis and fragility fractures. Current therapies for prevention of osteoporosis target osteoclastic bone resorption in the main, but these agents have limited ability to improve bone mass. There is great interest, therefore, in agents that may positively affect bone mass by stimulating bone formation.Recently, the importance of nutritional hormones in maintaining skeletal health has been recognized. This is reflected in the lower prevalence of osteoporosis in those with obesity. Thus hormones circulating at higher levels in obesity have received attention as potential anabolic agents in bone, including the products of pancreatic ␤-cells and of adipocytes. Obesity is associated with hyperinsulinemia, arising from resistance to the hypoglycemic effects of insu...

Relationships between preptin and osteocalcin in obese, overweight, and normal weight adults

“…On the other hand, preptin is anabolic to bone and may contribute to the preservation of bone mass observed in hyperinsulinemic states such as obesity (Cornish et al 2007). The reciprocal relationships between osteocalcin and systemic energy metabolism have been hypothesized as relating to the common origin of the osteoblast and the other cells involved in glucose and fat metabolism (i.e., adipocytes and muscle cells) (Chamberlain et al 2007).…”

“…Furthermore, there is convincing evidence showing that there is a bidirectional regulation between energy metabolism and bone tissue (Lee et al 2007;Confavreux et al 2009), whereby preptin influences osteoblast functions (Cornish et al 2007), and osteocalcin, in turn, influences energy metabolism (Lee et al 2007). The aim of this study was to investigate circulating preptin and osteocalcin levels and the possible association between them in obese and overweight adults.…”

Poor Trabecular Microarchitecture at the Distal Radius in Older Men with Increased Concentration of High-Sensitivity C-Reactive Protein—The Strambo Study

“…Obesity is associated with higher secretion of insulin, amylin, and preptin, which exert a protective effect on bone [48][49][50][51]. Adipocytes also secrete leptin and aromatize androgens to estrogens.…”

New insulin-like growth factor (IGF)-precursor sequences from mammalian genomes: the molecular evolution of IGFs and associated peptides in primates

“…A peptide corresponding to residues 2-35 of the E-domain, named preptin, is secreted from rat pancreatic islet beta cells, enhances insulin secretion [6] and has osteogenic properties [9]. This lies within the conserved part of the sequence (Fig.…”