title: Pancreatic PYY Is Critical in the Control of Insulin Secretion and Glucose Homeostasis in Female Mice.
abstract: Insulin secretion is tightly controlled through coordinated actions of a number of systemic and local factors. Peptide YY (PYY) is expressed in α-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 (Pyy(tg/+)/Rip-Cre) overexpressing the Pyy gene under the control of the rat insulin 2 gene promoter and assessed the impact of islet-released PYY on β-cell function, insulin release, and glucose homeostasis in mice. Our results show that up-regulation of PYY in islet β-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 respiratory exchange ratio. Mechanistically, the enhanced insulin levels and improved glucose tolerance are primarily due to increased β-cell mass and secretion. This is associated with alterations in the expression of genes important for β-cell proliferation and function as well as the maintenance of the β-cell phenotype. Taken together, these data demonstrate that pancreatic islet-derived PYY plays an important role in controlling glucose homeostasis through the modulation of β-cell mass and function.
authors.affiliation: Neuroscience (Y.-C.S., K.Lo., K.Le., L.Z., J.La., H.H.) and Diabetes and Metabolism (M.B., J.C., J.Lu., D.R.L.) Divisions, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst NSW 2010, Sydney, Australia; Faculty of Medicine (Y.-C.S., K.Lo., J.C., D.R.L., H.H.), UNSW Australia, Sydney, NSW, 2052 Australia; and Department of Physiology, Anatomy and Genetics (J.C.), University of Oxford, Oxford, OX1 3QX United Kingdom.
authors.forename: Yan-Chuan
authors.initials: YC
authors.lastname: Shi
authors.affiliation: Neuroscience (Y.-C.S., K.Lo., K.Le., L.Z., J.La., H.H.) and Diabetes and Metabolism (M.B., J.C., J.Lu., D.R.L.) Divisions, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst NSW 2010, Sydney, Australia; Faculty of Medicine (Y.-C.S., K.Lo., J.C., D.R.L., H.H.), UNSW Australia, Sydney, NSW, 2052 Australia; and Department of Physiology, Anatomy and Genetics (J.C.), University of Oxford, Oxford, OX1 3QX United Kingdom.
authors.forename: Kim
authors.initials: K
authors.lastname: Loh
authors.affiliation: Neuroscience (Y.-C.S., K.Lo., K.Le., L.Z., J.La., H.H.) and Diabetes and Metabolism (M.B., J.C., J.Lu., D.R.L.) Divisions, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst NSW 2010, Sydney, Australia; Faculty of Medicine (Y.-C.S., K.Lo., J.C., D.R.L., H.H.), UNSW Australia, Sydney, NSW, 2052 Australia; and Department of Physiology, Anatomy and Genetics (J.C.), University of Oxford, Oxford, OX1 3QX United Kingdom.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Bensellam
authors.affiliation: Neuroscience (Y.-C.S., K.Lo., K.Le., L.Z., J.La., H.H.) and Diabetes and Metabolism (M.B., J.C., J.Lu., D.R.L.) Divisions, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst NSW 2010, Sydney, Australia; Faculty of Medicine (Y.-C.S., K.Lo., J.C., D.R.L., H.H.), UNSW Australia, Sydney, NSW, 2052 Australia; and Department of Physiology, Anatomy and Genetics (J.C.), University of Oxford, Oxford, OX1 3QX United Kingdom.
authors.forename: Kailun
authors.initials: K
authors.lastname: Lee
authors.affiliation: Neuroscience (Y.-C.S., K.Lo., K.Le., L.Z., J.La., H.H.) and Diabetes and Metabolism (M.B., J.C., J.Lu., D.R.L.) Divisions, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst NSW 2010, Sydney, Australia; Faculty of Medicine (Y.-C.S., K.Lo., J.C., D.R.L., H.H.), UNSW Australia, Sydney, NSW, 2052 Australia; and Department of Physiology, Anatomy and Genetics (J.C.), University of Oxford, Oxford, OX1 3QX United Kingdom.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhai
authors.affiliation: Neuroscience (Y.-C.S., K.Lo., K.Le., L.Z., J.La., H.H.) and Diabetes and Metabolism (M.B., J.C., J.Lu., D.R.L.) Divisions, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst NSW 2010, Sydney, Australia; Faculty of Medicine (Y.-C.S., K.Lo., J.C., D.R.L., H.H.), UNSW Australia, Sydney, NSW, 2052 Australia; and Department of Physiology, Anatomy and Genetics (J.C.), University of Oxford, Oxford, OX1 3QX United Kingdom.
authors.forename: Jackie
authors.initials: J
authors.lastname: Lau
authors.affiliation: Neuroscience (Y.-C.S., K.Lo., K.Le., L.Z., J.La., H.H.) and Diabetes and Metabolism (M.B., J.C., J.Lu., D.R.L.) Divisions, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst NSW 2010, Sydney, Australia; Faculty of Medicine (Y.-C.S., K.Lo., J.C., D.R.L., H.H.), UNSW Australia, Sydney, NSW, 2052 Australia; and Department of Physiology, Anatomy and Genetics (J.C.), University of Oxford, Oxford, OX1 3QX United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Cantley
authors.affiliation: Neuroscience (Y.-C.S., K.Lo., K.Le., L.Z., J.La., H.H.) and Diabetes and Metabolism (M.B., J.C., J.Lu., D.R.L.) Divisions, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst NSW 2010, Sydney, Australia; Faculty of Medicine (Y.-C.S., K.Lo., J.C., D.R.L., H.H.), UNSW Australia, Sydney, NSW, 2052 Australia; and Department of Physiology, Anatomy and Genetics (J.C.), University of Oxford, Oxford, OX1 3QX United Kingdom.
authors.forename: Jude
authors.initials: J
authors.lastname: Luzuriaga
authors.affiliation: Neuroscience (Y.-C.S., K.Lo., K.Le., L.Z., J.La., H.H.) and Diabetes and Metabolism (M.B., J.C., J.Lu., D.R.L.) Divisions, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst NSW 2010, Sydney, Australia; Faculty of Medicine (Y.-C.S., K.Lo., J.C., D.R.L., H.H.), UNSW Australia, Sydney, NSW, 2052 Australia; and Department of Physiology, Anatomy and Genetics (J.C.), University of Oxford, Oxford, OX1 3QX United Kingdom.
authors.forename: D Ross
authors.initials: DR
authors.lastname: Laybutt
authors.affiliation: Neuroscience (Y.-C.S., K.Lo., K.Le., L.Z., J.La., H.H.) and Diabetes and Metabolism (M.B., J.C., J.Lu., D.R.L.) Divisions, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst NSW 2010, Sydney, Australia; Faculty of Medicine (Y.-C.S., K.Lo., J.C., D.R.L., H.H.), UNSW Australia, Sydney, NSW, 2052 Australia; and Department of Physiology, Anatomy and Genetics (J.C.), University of Oxford, Oxford, OX1 3QX United Kingdom.
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
mesh_terms: D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008822:Mice, Transgenic; D019894:Peptide YY / Q000378:metabolism*
chemical_list: D007328:Insulin; D019894:Peptide YY; D005947:Glucose