Vitamin B12 deficiency induces glucose intolerance, delays peak insulin levels and promotes ketogenesis in female rats

in Journal of Endocrinology
Authors:
Elliott S NealSchool of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia

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Vinod KumarSchool of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia

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Karin BorgesSchool of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia

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James S M CuffeSchool of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia

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Correspondence should be addressed to J Cuffe: j.cuffe1@uq.edu.au
DOI:
https://doi.org/10.1530/JOE-22-0158
Volume/Issue:
Volume 256: Issue 2
Article Type:
Research Article
Article ID:
e220158
Online Publication Date:
19 Jan 2023
Copyright:
© Society for Endocrinology 2023
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Vitamin B12 (B12) deficiency is common among individuals with diabetes mellitus, but it is unknown if B12 deficiency contributes to impaired glucose homeostasis in this disorder. Female Sprague–Dawley rats were assigned to a control or B12-deficient diet for 4 weeks. Intraperitoneal glucose tolerance tests were performed after 25 days, and blood and liver samples were collected for metabolic profiling. B12 deficiency resulted in a prediabetic-like phenotype characterised by glucose intolerance, a delayed peak in plasma insulin levels following a glucose challenge and increased ketogenesis. We attributed increased ketogenesis to reduced liver anaplerosis, which limited the availability of the TCA cycle intermediates citrate, succinate and succinyl-CoA. This was associated with increased Mut mRNA levels and citrate synthase activity in the liver. One-carbon metabolite levels were altered in plasma and the liver, which was linked to reduced methylation capacity, altered amino acid levels and elevated Slc7a5 mRNA expression. Plasma folate and biotin levels were reduced, as were the majority of B vitamins in the liver. Changes in these B12-dependent processes and reduced B vitamin amounts likely contributed to deficits in glucose handling. Our findings highlight that B12 deficiency may promote the development of metabolic disorders like diabetes mellitus and emphasise the importance of adequate B12 intake for metabolic health.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© Society for Endocrinology 2023
Article ID:
e220158
Article Type:
Research Article
Received Date:
06 Nov 2022
Accepted Date:
07 Dec 2022
Print Publication Date:
01 Feb 2023
Online Publication Date:
19 Jan 2023
Keywords:
cobalamin; diabetes mellitus; liver; mitochondria; anaplerosis; tricarboxylic (TCA) cycle; one-carbon metabolism

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