BibTeX
CSL-JSON
MLA
Harvard
High-resolution glucose fate-mapping reveals LDHB-dependent lactate production by human pancreatic β cells
release_cguhkf7vgreotbjgkjzeso75ku
by
Federica Cuozzo,
Daniela Nasteska,
Zicong Jiao,
Hannah R Smith,
Caroline Bonner,
Julie Kerr-Conte,
Francois Pattou,
Rita Nano,
Lorenzo Piemonti,
Jennie Roberts,
Gareth G Lavery,
Ildem Akerman
(+3 others)
Released
as a post
by Cold Spring Harbor Laboratory.
2022
Abstract
Using 13C6 glucose labeling coupled to GC-MS and 2D 1H-13C HSQC NMR spectroscopy, we have obtained a comparative high-resolution map of glucose fate underpinning steady state insulin release and β cell function. In both mouse and human islets, the contribution of glucose to the TCA cycle is similar. Pyruvate-fueling of the TCA cycle is found to be mediated primarily by the activity of pyruvate dehydrogenase (PDH), with only a limited contribution from pyruvate carboxylase (PC). While conversion of pyruvate to lactate by lactate dehydrogenase (LDH) can be detected in both species, lactate accumulation via this route is six-fold higher in human islets. Transcriptomic analysis reveals that human β cells specifically express lactate dehydrogenase B (LDHB) at high levels, in keeping with the phenotype of patients harboring gain-of-function mutations in MCT1/ SLC16A1 (HHF7). Thus, glycolytically-derived acetyl CoA preferentially feeds the TCA cycle in both mouse and human β cells. However, human β cells possess the machinery needed to generate extra-mitochondrial lactate, which might reflect a key mechanism to balance the reducing activity of NADH-producing pathways.
In application/xml+jats format
Archived Files and Locations
application/pdf
992.8 kB
file_bukggycb2bf4bgbtqk7fhafl4y
|
www.biorxiv.org (repository) web.archive.org (webarchive) |
Read Archived PDF
Preserved and Accessible
Type
Stage
Date 2022-12-21
postStage
unknown
Date 2022-12-21
Work Entity
access all versions, variants, and formats of this works (eg, pre-prints)
access all versions, variants, and formats of this works (eg, pre-prints)
Cite This
Lookup Links
oaDOI/unpaywall (OA fulltext)
Crossref Metadata (via API)
Worldcat
wikidata.org
CORE.ac.uk
Semantic Scholar
Google Scholar
Crossref Metadata (via API)
Worldcat
wikidata.org
CORE.ac.uk
Semantic Scholar
Google Scholar