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Endocrine Abstracts (2021) 77 P172 | DOI: 10.1530/endoabs.77.P172

SFEBES2021 Poster Presentations Metabolism, Obesity and Diabetes (78 abstracts)

ATP-Binding Cassette Subfamily C Member 1 (ABCC1) influences adiposity, glucose homeostasis and insulin sensitivity

Elisa Villalobos 1 , EE June Chua 2 , Allende Miguelez-Crespo 1 , Ruth Morgan 1 , Ruth Andrew 1 , Mark Nixon 1 & Brian Walker 1,3

1British Heart Foundation Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom; 2Edinburgh Medical School, Biomedical Science, University of Edinburgh, Edinburgh, United Kingdom; 3Clinical and Translational Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom

Background: Glucocorticoids (GCs) modulate glucose homeostasis by acting on metabolic tissues including liver, adipose, and skeletal muscle. ABCC1 is a transmembrane ‘drug-resistance’ transporter expressed in adipose tissue and skeletal muscle with previously unknown physiological function. We recently showed that ABCC1 modulates intracellular GC concentrations and action in adipose. Here, we tested the hypothesis that Abcc1 regulates GC concentrations in skeletal muscle as well as adipose, andinfluences glucose metabolism and insulin sensitivity.

Methods: Global Abcc1 knockout (Abcc1-/-)and wild-type mice were fed with chow diet or high-fat diet (HFD; 58% fat and sucrose) for 9 weeks before glucose and insulin tolerance tests and sampling for plasma and tissue GC concentrations measured by Liquid Chromatography Tandem Mass Spectrometry, and tissue GC-responsive markers (mRNA and protein) by RT-qPCR and Western blot.

Results: On chow diet, deletion of Abcc1 increased levels of corticosterone in plasma, subcutaneous adipose tissue (sWAT), and gastrocnemius muscle. This was accompanied by reduced total body fat mass (sWAT, gWAT and BAT) and lower fasting plasma insulin, with normal glucose tolerance. Reduced LplmRNA in sWAT, but not muscle, suggests Abcc1-/-mice have lower lipid uptake in adipose. On HFD fat mass gain was comparable between genotypes, but Abcc1-/-mice developed impaired glucose and insulin tolerance, and hyperinsulinemia. Strikingly, this worsened metabolic phenotype presents without measurable alterations in plasma or tissue GC levels.

Conclusions: These results suggest that ABCC1 influences adiposity, glucose metabolism, and insulin sensitivity by mechanisms which are likely to be GC-dependent only in part. These results introduce ABC transmembrane transporters as novel regulators of metabolic function.

Volume 77

Society for Endocrinology BES 2021

Edinburgh, United Kingdom
08 Nov 2021 - 10 Nov 2021

Society for Endocrinology 

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