ArticleMolecular metabolism2019
Acute β-adrenoceptor mediated glucose clearance in brown adipose tissue; a distinct pathway independent of functional insulin signaling.
Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 27 citations in OpenAlex.
- Brown adipose tissue and skeletal muscle coordinately contribute to thermogenesis in mice.eLife · 2025Article
- Glucose sensing and homeostasis by adipocyte GPCR.Frontiers in endocrinology · 2025Review
- Brown Adipose Tissue-A Translational Perspective.Endocrine reviews · 2023Review
- Recent insights into the molecular mechanisms of simultaneous fatty acid oxidation and synthesis in brown adipocytes.Frontiers in endocrinology · 2023Review
- Generation of mega brown adipose tissue in adults by controlling brown adipocyte differentiation in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Sympathetic Innervation of White Adipose Tissue: to Beige or Not to Beige?Physiology (Bethesda, Md.) · 2021Article
- Vanadium-dependent activation of glucose transport in adipocytes by catecholamines is not mediatedWorld journal of diabetes · 2020Article
- Brown Adipose Expansion and Remission of Glycemic Dysfunction in Obese SM/J Mice.Cell reports · 2020Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveβ-adrenoceptor mediated activation of brown adipose tissue (BAT) has been associated with improvements in metabolic health in models of type 2 diabetes and obesity due to its unique ability to increase whole body energy expenditure, and rate of glucose and free fatty acid disposal. While the thermogenic arm of this phenomenon has been studied in great detail, the underlying mechanisms involved in β-adrenoceptor mediated glucose uptake in BAT are relatively understudied. As β-adrenoceptor agonist administration results in increased hepatic gluconeogenesis that can consequently result in secondary pancreatic insulin release, there is uncertainty regarding the importance of insulin and the subsequent activation of its downstream effectors in mediating β-adrenoceptor stimulated glucose uptake in BAT. Therefore, in this study, we made an effort to discriminate between the two pathways and address whether the insulin signaling pathway is dispensable for the effects of β-adrenoceptor activation on glucose uptake in BAT.
methodsUsing a specific inhibitor of phosphoinositide 3-kinase α (PI3Kα), which effectively inhibits the insulin signaling pathway, we examined the effects of various β-adrenoceptor agonists, including the physiological endogenous agonist norepinephrine on glucose uptake and respiration in mouse brown adipocytes in vitro and on glucose clearance in mice in vivo.
resultsPI3Kα inhibition in mouse primary brown adipocytes in vitro, did not inhibit β-adrenoceptor stimulated glucose uptake, GLUT1 synthesis, GLUT1 translocation or respiration. Furthermore, β-adrenoceptor mediated glucose clearance in vivo did not require insulin or Akt activation but was attenuated upon administration of a β
conclusionsWe conclude that the β-adrenergic pathway is still functionally intact upon the inhibition of PI3Kα, showing that the activation of downstream insulin effectors is not required for the acute effects of β-adrenoceptor agonists on glucose homeostasis or thermogenesis.
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