Journal article
Abcc5 knockout mice have lower fat mass and increased levels of circulating GLP‐1
- Abstract:
-
Objective A previous genome‐wide association study linked overexpression of an ATP‐binding cassette transporter, ABCC5, in humans with a susceptibility to developing type 2 diabetes with age. Specifically, ABCC5 gene overexpression was shown to be strongly associated with increased visceral fat mass and reduced peripheral insulin sensitivity. Currently, the role of ABCC5 in diabetes and obesity is unknown. This study reports the metabolic phenotyping of a global Abcc5 knockout mouse.
Methods A global Abcc5‐/‐ mouse was generated by CRISPR/Cas9. Fat mass was determined by weekly EchoMRI and fat pads were dissected and weighed at week 18. Glucose homeostasis was ascertained by an oral glucose tolerance test, intraperitoneal glucose tolerance test, and intraperitoneal insulin tolerance test. Energy expenditure and locomotor activity were measured using PhenoMaster cages. Glucagon‐like peptide 1 (GLP‐1) levels in plasma, primary gut cell cultures, and GLUTag cells were determined by enzyme‐linked immunosorbent assay.
Results Abcc5‐/‐ mice had decreased fat mass and increased plasma levels of GLP‐1, and they were more insulin sensitive and more active. Recombinant overexpression of ABCC5 protein in GLUTag cells decreased GLP‐1 release.
Conclusions ABCC5 protein expression levels are inversely related to fat mass and appear to play a role in the regulation of GLP‐1 secretion from enteroendocrine cells.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 1.8MB, Terms of use)
-
- Publisher copy:
- 10.1002/oby.22521
Authors
+ Biotechnology and Biological Sciences Research Council
More from this funder
- Funding agency for:
- Cyranka, M
- De Wet, H
- Grant:
- BB/P020666/1
- BB/P020666/1
+ Physiological Society
More from this funder
- Funding agency for:
- Cyranka, M
- De Wet, H
- Grant:
- BB/P020666/1
- BB/P020666/1
+ John Fell Fund
More from this funder
- Funding agency for:
- Cyranka, M
- De Wet, H
- Grant:
- BB/P020666/1
- BB/P020666/1
- Publisher:
- Wiley
- Journal:
- Obesity More from this journal
- Volume:
- 27
- Issue:
- 8
- Pages:
- 1292-1304
- Publication date:
- 2019-07-24
- Acceptance date:
- 2019-04-09
- DOI:
- EISSN:
-
1930-739X
- ISSN:
-
1930-7381
- Pmid:
-
31338999
- Language:
-
English
- Pubs id:
-
pubs:1036789
- UUID:
-
uuid:66a660c8-b712-4a61-afb9-64ba64aa795f
- Local pid:
-
pubs:1036789
- Source identifiers:
-
1036789
- Deposit date:
-
2019-08-02
Terms of use
- Copyright holder:
- Cyranka et al
- Copyright date:
- 2019
- Notes:
- © 2019 The Authors Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS). This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record