Pleiotrophin Expression and Actions in Pancreatic β-Cells.

Julio Sevillano,Brenda Strutt,David J. Hill,Aileen Liang,Maria Pilar Ramos-Álvarez,Thomas G. Hill,Sandra Szlapinski

doi:10.3389/fendo.2022.777868

Abstract

Pleiotrophin (PTN) is a heparin-binding cytokine that is widely expressed during early development and increases in maternal circulation during pregnancy.Aged PTN-deficient mice exhibit insulin resistance, suggesting a role in metabolic control. The objectives of this study were to determine if PTN is expressed in mouse pancreatic β-cells in young vs. adult animals, and its effects on DNA synthesis, β-cell gene expression and glucose-stimulated insulin secretion (GSIS). The Ptn gene was expressed in isolated fractions of young mouse β-cells, especially within immature β-cells with low glucose transporter 2 expression. Expression was retained in the adult pancreas but did not significantly change during pregnancy. PTN and its receptor, phosphotyrosine phosphatase-β/ζ, were also expressed in the proliferative INS1E β-cell line. Fluorescence immunohistochemistry showed that PTN peptide was present in islets of Langerhans in adult mice, associated predominantly with β-cells. The percentage of β-cells staining for PTN did not alter during mouse pregnancy, but intense staining was seen during β-cell regeneration in young mice following depletion of β-cells with streptozotocin. Incubation of INS1E cells with PTN resulted in an increased DNA synthesis as measured by Ki67 localization and increased expression of Pdx1 and insulin. However, both DNA synthesis and GSIS were not altered by PTN in isolated adult mouse islets. The findings show that Ptn is expressed in mouse β-cells in young and adult life and could potentially contribute to adaptive increases in β-cell mass during early life or pregnancy.

Highlights

Pleiotrophin (PTN) is a heparin-binding cytokine that is highly conserved across mammalian species [1, 2]
In this study we have examined the expression and presence of PTN in young and adult mouse pancreas, how this might alter during pregnancy and the actions of PTN on b-cell DNA synthesis and glucose-stimulated insulin release
We examined b-cells isolated by fluorescence-activated cell sorting (FACS) from the young mouse pancreas for Ptn and Ptprz1 mRNA presence and found both (Table 1)

Summary

Introduction

Pleiotrophin (PTN) is a heparin-binding cytokine that is highly conserved across mammalian species [1, 2]. It is expressed in multiple tissues during embryonic and fetal development and is important for tissue growth and morphogenesis in organs that undergo branching morphogenesis [3, 4]. The pancreas is one such organ where branching ductal morphogenesis gives rise to endocrine, acinar and ductal cell lineages [5]. In particular PTN contributes to cell proliferation and angiogenesis and, in the embryonic pancreas, Ptn is expressed in areas of vasculogenesis adjacent to the differentiating ductal epithelium. Pleiotrophin and Pancreatic b-Cells of Ptn expression resulted in a failure of endocrine precursors to fully differentiate and express insulin or glucagon [6]. By E11-13 Ptn expression becomes limited to the pancreatic epithelium and PTN is localized to the basement membranes, especially associated with islet budding from the ductal epithelium

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