Premium
Tau ablation in mice leads to pancreatic β cell dysfunction and glucose intolerance
Author(s) -
Wijesekara Nadeeja,
Gonçalves Rafaella Araujo,
Ahrens Rosemary,
De Felice Fernanda G.,
Fraser Paul E.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201701352
Subject(s) - medicine , endocrinology , glucose homeostasis , proinsulin , islet , genetically modified mouse , pancreatic islets , diabetes mellitus , insulin , homeostasis , pancreas , insulin resistance , knockout mouse , transgene , impaired glucose tolerance , biology , chemistry , receptor , biochemistry , gene
The microtubule‐associated protein tau is highly expressed in pancreatic islets. Abnormally phosphorylated tau aggregates assemble into neurofibrillary tangles linked to Alzheimer's disease pathology and has also been found in islets of patients with type 2 diabetes. However, the significance of tau in islet function remains relatively unexplored. Therefore, we investigated the role of tau on β cell function and glucose homeostasis using tau knockout (tauKO) mice. TauKO mice were hyperglycemic and glucose intolerant at an early age. Islet insulin content was reduced and proinsulin levels were significantly elevated in tauKO mice, resulting in impaired glucose‐stimulated insulin secretion. Loss of tau also resulted in increased epididymal fat mass and leptin levels, reduced glucose production, and insulin resistance at later ages, leading to complete onset of diabetes. Transgenic expression of human tau in islets was unable to rescue those defects in glucose regulation, indicating structural and/or functional differences between mouse and human tau. Cumulatively, these results suggest an important role for tau in the proper maintenance of pancreatic β cell function and glucose homeostasis.—Wijesekara, N., Gonçalves, R. A., Ahrens, R., De Felice, F. G., Fraser, P. E. Tau ablation in mice leads to pancreatic β cell dysfunction and glucose intolerance. FASEB J. 32, 3166–3173 (2018). www.fasebj.org