Open AccessWingless-Type MMTV Integration Site Family Member 5a Is a Key Secreted Islet Stellate Cell-Derived Product that Regulates Islet Function
Author(s) -
Wei Xu,
Jun Liang,
Hao Geng,
Jun Lü,
Rui Li,
X. L. Wang,
Qian Lei,
Ying Liu,
Jie Wang,
X. K. Liu,
Peter M. Jones,
Zilin Sun
Publication year - 2019
Publication title -
international journal of endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.875
H-Index - 60
eISSN - 1687-8345
pISSN - 1687-8337
DOI - 10.1155/2019/7870109
Subject(s) - islet , secretion , insulin , endocrinology , microbiology and biotechnology , medicine , hepatic stellate cell , glucose homeostasis , effector , downregulation and upregulation , rna interference , biology , rna , gene , insulin resistance , genetics
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.