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A novel role of the corticotrophin‐releasing hormone regulating peptide, teneurin C‐terminal associated peptide 1, on glucose uptake into the brain
Author(s) -
Hogg D. W.,
Chen Y.,
D'Aquila A. L.,
Xu M.,
Husić M.,
Tan L. A.,
Bull C.,
Lovejoy D. A.
Publication year - 2018
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12579
Subject(s) - medicine , endocrinology , glucose uptake , glucose transporter , biology , insulin , neuroprotection , carbohydrate metabolism
Teneurin C‐terminal associated peptide ( TCAP ) is an ancient paracrine signalling agent that evolved via lateral gene transfer from prokaryotes into an early metazoan ancestor. Although it bears structural similarity to corticotrophin‐releasing hormone ( CRH ), it inhibits the in vivo actions of CRH . The TCAP s are highly expressed in neurones, where they induce rapid cytoskeletal rearrangement and are neuroprotective. Because these processes are highly energy‐dependent, this suggests that TCAP has the potential to regulate glucose uptake because glucose is the primary energy substrate in brain, and neurones require a steady supply to meet the high metabolic demands of neuronal communication. Therefore, the objective of the present study was to assess the effect of TCAP ‐mediated glucose uptake in the brain and in neuronal cell models. TCAP ‐mediated 18 F‐deoxyglucose ( FDG ) uptake into brain tissue was assessed in male wild‐type Wistar rats by functional positron emission tomography. TCAP ‐1 increased FDG uptake by over 40% into cortical regions of the brain, demonstrating that TCAP ‐1 can significantly enhance glucose supply. Importantly, a single nanomolar injection of TCAP ‐1 increased brain glucose after 3 days and decreased blood glucose after 1 week. This is corroborated by a decreased serum concentration of insulin and an increased serum concentration of glucagon. In immortalised hypothalamic neurones, TCAP ‐1 increased ATP production and enhanced glucose uptake by increasing glucose transporter recruitment to the plasma membrane likely via AKT and mitogen‐activated protein kinase / ERK phosphorylation events. Taken together, these data demonstrate that TCAP ‐1 increases glucose metabolism in neurones, and may represent a peptide signalling agent that regulated glucose uptake before insulin and related peptides.