PMID- 32669482
OWN - NLM
STAT- MEDLINE
DCOM- 20210927
LR  - 20220805
IS  - 1348-4540 (Electronic)
IS  - 0918-8959 (Linking)
VI  - 67
IP  - 11
DP  - 2020 Nov 28
TI  - Rubicon in pancreatic beta cells plays a limited role in maintaining glucose 
      homeostasis following increased insulin resistance.
PG  - 1119-1126
LID - 10.1507/endocrj.EJ20-0326 [doi]
AB  - 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 betaTC3 pancreatic beta-cell line. Next, we generated pancreatic 
      beta-cell-specific Rubicon knockout (betaKO) mice, by administering tamoxifen to 
      Rubicon(flox/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 months to find little differences 
      among the parameters evaluated for glucose metabolism. Finally, severe insulin 
      resistance was induced with insulin receptor antagonist treatment, which resulted 
      in comparable glucose homeostasis measurements between Rubicon betaKO and control 
      mice. In summary, these results suggest that in pancreatic beta cells, Rubicon 
      plays a limited role in the maintenance of systemic glucose homeostasis.
FAU - Aoyama, Shuhei
AU  - Aoyama S
AD  - Department of Metabolism and Endocrinology, Juntendo University Graduate School 
      of Medicine, Tokyo 113-8421, Japan.
FAU - Nishida, Yuya
AU  - Nishida Y
AD  - Department of Metabolism and Endocrinology, Juntendo University Graduate School 
      of Medicine, Tokyo 113-8421, Japan.
AD  - Center for Therapeutic Innovations in Diabetes, Tokyo 113-8421, Japan.
FAU - Fujitani, Yoshio
AU  - Fujitani Y
AD  - Laboratory of Developmental Biology and Metabolism, Institute for Molecular and 
      Cellular Regulation, Gunma University, Gunma 371-8512, Japan.
FAU - Fukunaka, Ayako
AU  - Fukunaka A
AD  - Laboratory of Developmental Biology and Metabolism, Institute for Molecular and 
      Cellular Regulation, Gunma University, Gunma 371-8512, Japan.
FAU - Miyatsuka, Takeshi
AU  - Miyatsuka T
AD  - Department of Metabolism and Endocrinology, Juntendo University Graduate School 
      of Medicine, Tokyo 113-8421, Japan.
AD  - Center for Identification of Diabetic Therapeutic Targets, Tokyo 113-8421, Japan.
FAU - Suzuki, Luka
AU  - Suzuki L
AD  - Department of Metabolism and Endocrinology, Juntendo University Graduate School 
      of Medicine, Tokyo 113-8421, Japan.
AD  - Center for Identification of Diabetic Therapeutic Targets, Tokyo 113-8421, Japan.
FAU - Himuro, Miwa
AU  - Himuro M
AD  - Department of Metabolism and Endocrinology, Juntendo University Graduate School 
      of Medicine, Tokyo 113-8421, Japan.
AD  - Center for Identification of Diabetic Therapeutic Targets, Tokyo 113-8421, Japan.
FAU - Yoshimori, Tamotsu
AU  - Yoshimori T
AD  - Department of Intracellular Membrane Dynamics, Graduate School of Frontier 
      Biosciences, Osaka University, Osaka 565-0871, Japan.
FAU - Watada, Hirotaka
AU  - Watada H
AD  - Department of Metabolism and Endocrinology, Juntendo University Graduate School 
      of Medicine, Tokyo 113-8421, Japan.
AD  - Center for Therapeutic Innovations in Diabetes, Tokyo 113-8421, Japan.
AD  - Center for Identification of Diabetic Therapeutic Targets, Tokyo 113-8421, Japan.
LA  - eng
PT  - Journal Article
DEP - 20200716
PL  - Japan
TA  - Endocr J
JT  - Endocrine journal
JID - 9313485
RN  - 0 (Blood Glucose)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Rubcn protein, mouse)
SB  - IM
MH  - Animals
MH  - Autophagy/*genetics
MH  - Blood Glucose/*metabolism
MH  - Cell Line, Tumor
MH  - Gene Knockdown Techniques
MH  - Homeostasis
MH  - Insulin Resistance/*genetics
MH  - Insulin-Secreting Cells/*metabolism
MH  - Intracellular Signaling Peptides and Proteins/*genetics
MH  - Mice
MH  - Mice, Knockout
OTO - NOTNLM
OT  - Autophagy
OT  - Insulin resistance
OT  - PI3K
OT  - Pancreatic beta cells
OT  - Rubicon
EDAT- 2020/07/17 06:00
MHDA- 2021/09/28 06:00
CRDT- 2020/07/17 06:00
PHST- 2020/07/17 06:00 [pubmed]
PHST- 2021/09/28 06:00 [medline]
PHST- 2020/07/17 06:00 [entrez]
AID - 10.1507/endocrj.EJ20-0326 [doi]
PST - ppublish
SO  - Endocr J. 2020 Nov 28;67(11):1119-1126. doi: 10.1507/endocrj.EJ20-0326. Epub 2020 
      Jul 16.