Pancreatic PYY is critical in the control of insulin secretion and glucose homeostasis in female mice — ASN Events

Pancreatic PYY is critical in the control of insulin secretion and glucose homeostasis in female mice (#258)

Kim Loh 1 , Mohammed Bensellam 1 , Kailun Lee 1 , Lei Zhai 1 , Jackie Lau 1 , James Cantley 2 , Jude Luzuriaga 1 , D. Ross Laybutt 1 , Herbert Herzog 1 , Yan-Chuan Shi 1
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK

Insulin secretion is tightly controlled through coordinated actions of a number of systemic and local factors. Peptide YY (PYY) is expressed in alpha cells of the islet but its role in control of islet function such as insulin release is not clear. In this study, we generated a transgenic mouse model (Pyytg/+/Rip-Cre) overexpressing the Pyy gene under the control of the rat insulin 2 (Ins2) gene promoter and assessed the impact of islet-released PYY on beta cell function, insulin release and glucose homeostasis in mice. Our results show that upregulation of PYY in islet beta-cells leads to an increase in serum insulin levels as well as improved glucose tolerance. Interestingly, PYY overproducing mice show increased lean mass and reduced fat mass with no significant changes in food intake or body weight. Energy expenditure is also increased accompanied by increased RER. Mechanistically, the enhanced in insulin levels and improved in glucose tolerance are primarily due to increased beta cell mass and secretion. This is associated with alterations in the expression of genes important for beta cell proliferation and function as well as the maintenance of the beta cell phenotype. Taken together, these data demonstrate that pancreatic islet-derived PYY plays an important role in controlling glucose homeostasis through the modulation of beta cell mass and function.