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Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1.
Cyranka, Malgorzata; Veprik, Anna; McKay, Eleanor J; van Loon, Nienke; Thijsse, Amber; Cotter, Luke; Hare, Nisha; Saibudeen, Affan; Lingam, Swathi; Pires, Elisabete; Larraufie, Pierre; Reimann, Frank; Gribble, Fiona; Stewart, Michelle; Bentley, Elizabeth; Lear, Pamela; McCullagh, James; Cantley, James; Cox, Roger D; de Wet, Heidi.
Affiliation
  • Cyranka M; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Veprik A; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • McKay EJ; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • van Loon N; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Thijsse A; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Cotter L; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Hare N; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Saibudeen A; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Lingam S; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Pires E; Chemistry Research Laboratory, University of Oxford, Oxford, UK.
  • Larraufie P; Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
  • Reimann F; Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
  • Gribble F; Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
  • Stewart M; MRC Harwell Institute, Genetics of Type 2 Diabetes, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, UK.
  • Bentley E; MRC Harwell Institute, Genetics of Type 2 Diabetes, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, UK.
  • Lear P; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • McCullagh J; Chemistry Research Laboratory, University of Oxford, Oxford, UK.
  • Cantley J; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Cox RD; MRC Harwell Institute, Genetics of Type 2 Diabetes, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, UK.
  • de Wet H; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Obesity (Silver Spring) ; 27(8): 1292-1304, 2019 08.
Article in En | MEDLINE | ID: mdl-31338999
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Insulin Resistance / Adipose Tissue / Multidrug Resistance-Associated Proteins / Glucagon-Like Peptide 1 Limits: Animals Language: En Journal: Obesity (Silver Spring) Journal subject: CIENCIAS DA NUTRICAO / FISIOLOGIA / METABOLISMO Year: 2019 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Insulin Resistance / Adipose Tissue / Multidrug Resistance-Associated Proteins / Glucagon-Like Peptide 1 Limits: Animals Language: En Journal: Obesity (Silver Spring) Journal subject: CIENCIAS DA NUTRICAO / FISIOLOGIA / METABOLISMO Year: 2019 Document type: Article Affiliation country: