TY - JOUR
T1 - Pancreatic islet neuropeptide Y overexpression has minimal effect on islet morphology and β-cell adaptation to high-fat diet
AU - Machida, Yui
AU - Bruinsma, Christine
AU - Hallinger, Daniel R.
AU - Roper, Stephen M.
AU - Garcia, Eden
AU - Trevino, Michelle B.
AU - Nadler, Joseph
AU - Ahima, Rexford
AU - Imai, Yumi
N1 - Publisher Copyright:
Copyright © 2014 by the Endocrine Society
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84914166077&partnerID=8YFLogxK
U2 - 10.1210/en.2014-1537
DO - 10.1210/en.2014-1537
M3 - Article
C2 - 25285650
AN - SCOPUS:84914166077
SN - 0013-7227
VL - 155
SP - 4634
EP - 4640
JO - Endocrinology
JF - Endocrinology
IS - 12
ER -