High intensity exercise decreases IP6K1 muscle content & improves insulin sensitivity in glucose intolerant individuals

Naufahu, J., Elliott, B., Markiv, A., Dunning-Foreman, P., McGrady, M., Howard, D., Watt, P.W. and Mackenzie, R.W.A. 2018. High intensity exercise decreases IP6K1 muscle content & improves insulin sensitivity in glucose intolerant individuals. Journal of Clinical Endocrinology and Metabolism. 103 (4), pp. 1479-1490. https://doi.org/10.1210/jc.2017-02019

TitleHigh intensity exercise decreases IP6K1 muscle content & improves insulin sensitivity in glucose intolerant individuals
TypeJournal article
AuthorsNaufahu, J., Elliott, B., Markiv, A., Dunning-Foreman, P., McGrady, M., Howard, D., Watt, P.W. and Mackenzie, R.W.A.
Abstract

Context
Insulin resistance in skeletal muscle contributes to whole body hyperglycaemia and the secondary complications associated with type 2 diabetes. Inositol hexakisphosphate kinase-1 (IP6K1) may inhibit insulin-stimulated glucose transport in this tissue type.

Objective
Muscle and plasma IP6K1 were correlated with two-compartment models of glucose control in insulin-resistant hyperinsulimic individuals. Muscle IP6K1 was also compared following two different exercise trials.

Methods
Nine pre-diabetic [HbA1c; 6.1 (0.2) %)] were recruited to take part in a resting control, a continuous exercise (90% of lactate threshold) and a high-intensity exercise trial (6 x 30 sec sprints). Muscle biopsies were drawn pre- and post each 60-minute trial. A labeled ([6,62H2]glucose) intravenous glucose tolerance test (IVGTT) was performed immediately after the second muscle sample.

Results
Fasting muscle IP6K1 content did not correlate with SI2* (P = 0.961). High-intensity exercise reduced IP6K1 muscle protein and mRNA expression (P = 0.001). There was no effect on protein IP6K1 content following continuous exercise. Akt308 phosphorylation of was significantly greater following high-intensity exercise. Intermittent exercise reduced hepatic glucose production (HGP) following the same trial. The same intervention also improved SI2* and this was significantly greater compared to the continuous exercise improvements. Our in vitro experiment demonstrated that the chemical inhibition of IP6K1 increased insulin signaling in C2C12 myotubes.

Conclusions
The in vivo and in vitro approaches used in the current study suggest that a decrease in muscle IP6K1 may be linked to whole body improvements in SI2*. In addition, high-intensity exercise reduces HPG in insulin-resistant individuals.

JournalJournal of Clinical Endocrinology and Metabolism
Journal citation103 (4), pp. 1479-1490
ISSN0021-972X
Year2018
PublisherOxford University Press
Accepted author manuscript
Digital Object Identifier (DOI)https://doi.org/10.1210/jc.2017-02019
PubMed ID29300979
Web address (URL)https://academic.oup.com/jcem/advance-article/doi/10.1210/jc.2017-02019/4781494#.Wk1mGUDPy4U.twitter
Publication dates
Published in printApr 2018
Published online29 Dec 2017
Published29 Dec 2017
FunderSociety for Endocrinology

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