Wingless-type MMTV integration site family member 5a is a key secreted islet stellate cell-derived product that regulates islet function

TY - JOUR

T1 - Wingless-type MMTV integration site family member 5a is a key secreted islet stellate cell-derived product that regulates islet function

AU - Xu, Wei

AU - Liang, Jun

AU - Geng, H. F.

AU - Lu, Jun

AU - Li, Rui

AU - Wang, X. L.

AU - Lv, Qian

AU - Liu, Ying

AU - Wang, Jie

AU - Liu, X. K.

AU - Jones, Peter M.

AU - Sun, Zl

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background. Emerging evidence suggests that T2DM is attributable to the dysfunction of β-cells and the activation of islet stellate cells (ISCs). The wingless-type MMTV integration site family member 5a (Wnt5a)/frizzled 5 (Fzd5) signalling pathway might take part in this process. Our study is aimed at defining the status of ISCs during β-cell insulin secretion homeostasis by determining the role of the Wnt5a protein in the regulation of insulin production. We examined the effects of the status of ISCs on β-cell insulin secretion in normoglycemic db/m and hyperglycaemic db/db mice. Methods. iTRAQ protein screening and RNA interference were used to determine novel ISC-derived secretory products that may use other mechanisms to influence the function of islets. Results. We showed a significant reduction in insulin secretion by β-cells in vitro when they were cocultured with db/db ISCs compared to when they were cocultured with ISCs isolated from normoglycemic db/m mice; in addition, both Wnt5a and its receptor Fzd5 were more highly expressed by quiescent ISCs than by activated db/db ISCs. Treatment with exogenous Wnt5a increased the secretion of insulin in association with the deactivation of ISCs. Conclusion. Our observations revealed that the Wnt5a protein is a key effector of ISC-mediated improvement in islet function.

AB - Background. Emerging evidence suggests that T2DM is attributable to the dysfunction of β-cells and the activation of islet stellate cells (ISCs). The wingless-type MMTV integration site family member 5a (Wnt5a)/frizzled 5 (Fzd5) signalling pathway might take part in this process. Our study is aimed at defining the status of ISCs during β-cell insulin secretion homeostasis by determining the role of the Wnt5a protein in the regulation of insulin production. We examined the effects of the status of ISCs on β-cell insulin secretion in normoglycemic db/m and hyperglycaemic db/db mice. Methods. iTRAQ protein screening and RNA interference were used to determine novel ISC-derived secretory products that may use other mechanisms to influence the function of islets. Results. We showed a significant reduction in insulin secretion by β-cells in vitro when they were cocultured with db/db ISCs compared to when they were cocultured with ISCs isolated from normoglycemic db/m mice; in addition, both Wnt5a and its receptor Fzd5 were more highly expressed by quiescent ISCs than by activated db/db ISCs. Treatment with exogenous Wnt5a increased the secretion of insulin in association with the deactivation of ISCs. Conclusion. Our observations revealed that the Wnt5a protein is a key effector of ISC-mediated improvement in islet function.

UR - http://www.scopus.com/inward/record.url?scp=85071266419&partnerID=8YFLogxK

U2 - 10.1155/2019/7870109

DO - 10.1155/2019/7870109

M3 - Article

AN - SCOPUS:85071266419

SN - 1687-8337

VL - 2019

JO - International Journal of Endocrinology

JF - International Journal of Endocrinology

M1 - 7870109

ER -