SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:DiVA.org:umu-114567"
 

Search: onr:"swepub:oai:DiVA.org:umu-114567" > Asna1/TRC40 Control...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Asna1/TRC40 Controls beta-Cell Function and Endoplasmic Reticulum Homeostasis by Ensuring Retrograde Transport

Norlin, Stefan (author)
Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
Parekh, Vishal S. (author)
Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
Naredi, Peter (author)
show more...
Edlund, Helena (author)
Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
show less...
 (creator_code:org_t)
2015-10-05
2016
English.
In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 65:1, s. 110-119
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • Type 2 diabetes (T2D) is characterized by insulin resistance and beta-cell failure. Insulin resistance per se, however, does not provoke overt diabetes as long as compensatory beta-cell function is maintained. The increased demand for insulin stresses the beta-cell endoplasmic reticulum (ER) and secretory pathway, and ER stress is associated with beta-cell failure in T2D. The tail recognition complex (TRC) pathway, including Asna1/TRC40, is implicated in the maintenance of endomembrane trafficking and ER homeostasis. To gain insight into the role of Asna1/TRC40 in maintaining endomembrane homeostasis and beta-cell function, we inactivated Asnal in beta-cells of mice. We show that Asna1 beta(-/-) mice develop hypoinsulinemia, impaired insulin secretion, and glucose intolerance that rapidly progresses to overt diabetes. Loss of Asnal function leads to perturbed plasma membrane-to-trans Golgi network and Golgi-to-ER retrograde transport as well as to ER stress in beta-cells. Of note, pharmacological inhibition of retrograde transport in isolated islets and insulinoma cells mimicked the phenotype of Asna1(beta-/-) beta-cells and resulted in reduced insulin content and ER stress. These data support a model where Asnal ensures retrograde transport and, hence, ER and insulin homeostasis in beta-cells.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Publication and Content Type

ref (subject category)
art (subject category)

Find in a library

  • Diabetes (Search for host publication in LIBRIS)

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Find more in SwePub

By the author/editor
Norlin, Stefan
Parekh, Vishal S ...
Naredi, Peter
Edlund, Helena
About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Endocrinology an ...
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Cell and Molecul ...
Articles in the publication
Diabetes
By the university
Umeå University

Search outside SwePub

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view