title: Pancreatic islet neuropeptide Y overexpression has minimal effect on islet morphology and β-cell adaptation to high-fat diet.
abstract: Neuropeptide Y (NPY) is highly expressed in the hypothalamus, where it regulates feeding and energy homeostasis. Interestingly, NPY and its receptors are also expressed in peripheral tissues with roles in metabolism, including pancreatic islets. In islets, NPY is known to suppress insulin secretion acutely. In addition, the role of NPY in β-cell de-differentiation has been postulated recently. Therefore, we studied transgenic mice expressing NPY under rat insulin promoter (TG) to determine the effects of chronic up-regulation of NPY on islet morphology and function. NPY levels were 25 times higher in islets of TG mice compared with wild-type (WT) littermates, whereas no differences in NPY expression were noted in the brains of TG and WT mice. Islet NPY secretion was 2.3-fold higher in TG compared with WT mice. There were no significant changes in body weight, glucose tolerance, or insulin sensitivity in TG mice fed regular rodent diet or high-fat diet (HF). Islet β-cell area was comparable between TG and WT mice both on regular rodent and HF diets, indicating that NPY overexpression is insufficient to alter β-cell maturation or the compensatory increase of β-cell area on HF. One abnormality noted was that the glucose-stimulated insulin secretion in islets isolated from TG was reduced compared with those from WT mice on HF diet. Overall, an increase in islet NPY level has little impact on islet function and is insufficient to affect glucose homeostasis in mice.
authors.affiliation: Department of Internal Medicine (Y.M., C.B., D.R.H., S.M.R., E.G., M.B.T., J.N., Y.I.), Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, Virginia 23507; and Department of Medicine (R.A.), Division of Endocrinology, Diabetes, and Metabolism, and the Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Yui
authors.initials: Y
authors.lastname: Machida
authors.forename: Christine
authors.initials: C
authors.lastname: Bruinsma
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Hallinger
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Roper
authors.forename: Eden
authors.initials: E
authors.lastname: Garcia
authors.forename: Michelle B
authors.initials: MB
authors.lastname: Trevino
authors.forename: Joseph
authors.initials: J
authors.lastname: Nadler
authors.forename: Rexford
authors.initials: R
authors.lastname: Ahima
authors.forename: Yumi
authors.initials: Y
authors.lastname: Imai
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D059305:Diet, High-Fat; D005260:Female; D006706:Homeostasis; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D009478:Neuropeptide Y