High intensity exercise decreases IP6K1 muscle content & improves insulin sensitivity (SI2*) in glucose intolerant individuals.

High intensity exercise decreases IP6K1 muscle content & improves insulin sensitivity (SI2*) in glucose intolerant individuals.

J Clin Endocrinol Metab. 2017 Dec 29;:

Authors: Naufahu J, Elliott B, Markiv A, Dunning-Foreman P, McGrady M, Howard D, Watt P, Mackenzie RWA

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.

PMID: 29300979 [PubMed - as supplied by publisher]

http://ift.tt/2lXafpG