A role of FRK in regulation of embryonal pancreatic beta cell formation

Abstract

To cite this version:Björn Åkerblom, Cecilia Annerén, Michael Welsh. A role of frk in regulation of embryonal pancreatic beta cell formation. Molecular and Cellular Endocrinology, Elsevier, 2007, 270 (1-2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t 2 SummaryThe Fyn-Related-Kinase is a non-receptor tyrosine kinase expressed in various tissues, among them, the islets of Langerhans. The role of FRK in pancreatic beta cells has been addressed by studies of knockout or FRK-transgenic mice. These experiments have shown that FRK overexpression in beta cells leads to an increased susceptibility to the beta cell toxin streptozotocin and to cytotoxic cytokines, suggesting that FRK may participate in events leading to beta cell destruction.However, these mice also exhibit an increased relative beta cell volume and increased beta cell replication following partial pancreatectomy, suggesting a positive role for FRK in the regulation of beta cell number as well.To further assess the significance of FRK for beta cell replication, we studied the beta cell area and islet cell replication in FRK null mice. We currently observe that the FRK-knockout mouse showed no difference in the insulin positive cell area or in the percentage of Ki67-stained proliferating islet cells at adulthood, when compared to wild-type control. In addition, adult FRK-/-mice performed normally when subjected to an intravenous glucose tolerance test.To elucidate whether FRK affects pancreatic beta cell number during embryogenesis and shortly after birth, pancreata were collected from FRK-/-mice at these stages.Histological analysis of insulin stained pancreatic sections showed that the insulin positive cell area in FRK-/-mice was reduced at embryonal day 15 and at birth to 31% and 70% of that of wild-type mice, respectively. FRK -/-pancreas weight on day 1 neonatally was similar to that of the control, indicating that the obtained resultswere not due to altered pancreatic growth.Taken together these results show that FRK affects beta cell number during embryogenesis and early in life, but is probably redundant for beta cell number and function in adult animals under normal conditions.

METABOLIC PHENOTYPING GUIDELINES: Assessing glucose homeostasis in rodent models

“…Whilst i.v. administration into the tail vein is occasionally used for GTT tests (Akerblom et al 2007), it is more frequently used when experimental animals are implanted with intravenous catheters, usually for sampling purposes. In animals in which intravenous catheters are implanted, i.v.…”

Glial Cell Line-Derived Neurotrophic Factor Increases β-Cell Mass and Improves Glucose Tolerance

“…β-TC-6 cells were cultured in serum-free medium for 48 h followed by 24 h in the presence or absence of GDNF and assessed for proliferation by staining for the proliferation marker Ki67 17 . GDNF increased the number of Ki67 positive cells in a dose dependent fashion (Fig.…”

Kin of IRRE-like Protein 2 Is a Phosphorylated Glycoprotein That Regulates Basal Insulin Secretion

“…The role of Fyn in pancreatic ␤-cells is currently unknown; however, the related kinase YES has been shown to be required for granule mobilization/replenishment, and F-actin remodeling in sustained insulin secretion (63) and Fyn-related kinase FRK influences ␤-cell number during embryogenesis and neonatal life (64). In this study, we have shown that Fyn is also responsible for Kirrel2 phosphorylation in pancreatic ␤-cells.…”