Rubicon in pancreatic beta cells plays a limited role in maintaining glucose homeostasis following increased insulin resistance.

Rubicon in pancreatic beta cells plays a limited role in maintaining glucose homeostasis following increased insulin resistance. Endocr J. 2020 Jul 16;: Authors: Aoyama S, Nishida Y, Fujitani Y, Fukunaka A, Miyatsuka T, Suzuki L, Himuro M, Yoshimori T, Watada H Abstract Autophagy has been reported to play a crucial role in the maintenance of intracellular homeostasis, including in pancreatic beta cells. Rubicon, which interacts with the phosphoinositide 3-kinase (PI3K) complex, through autophagy-related 14 (ATG14), is among the few autophagy regulators that have been reported to inhibit autophagic flux to date and the deletion of Rubicon has been shown to increase autophagic flux. Based on previous results showing a causal relationship between autophagic dysfunction and pancreatic beta-cell impairment, we hypothesized that the deletion of Rubicon in pancreatic beta cells would improve cell integrity and confer protective effects. To test this hypothesis, we first confirmed that Rubicon knockdown (KD) promoted autophagic flux in βTC3 pancreatic beta-cell line. Next, we generated pancreatic beta-cell-specific Rubicon knockout (βKO) mice, by administering tamoxifen to Rubiconflox/flox:MIP-Cre-ERT mice, which showed normal glucose tolerance and insulin secretion under a normal chow diet, despite successful gene recombination. We also attempted to increase insulin resistance by feeding the mice with a high-fat diet for an additional 2 m...
Source: Endocrine Journal - Category: Endocrinology Tags: Endocr J Source Type: research