# Inositol hexakisphosphate kinase 1 is implicated in the insulin response to protein ingestion in older adults

## TL;DR

This study explores how IP6K1 levels in blood and muscle differ between young and older adults and their role in the body's response to protein and exercise.

## Contribution

The study identifies IP6K1 as a potential mediator of reduced amino acid metabolism and insulin response in older adults.

## Key findings

- Young adults had higher plasma IP6K1 levels compared to older adults at all time points.
- Older adults showed reduced muscle IP6K1 after exercise and in postprandial states.
- IP6K1 levels correlated with reduced amino acid metabolism and insulin response in older adults.

## Abstract

Age-related muscle mass is driven by a reduction in insulin sensitivity partly mediated by reduced amino acid and anabolic signalling kinetics. Insulin activates Akt-mTORC1 signalling in skeletal muscle, with inositol hexakisphosphate kinase 1 (IP6K1) shown to inhibit this signalling pathway in pre-diabetic humans. We aimed to compare muscle and plasma IP6K1 in young vs older adults and the possible role of IP6K1 in the anabolic response to protein and protein plus resistance exercise (RE). Nine young (24.9 ± 0.4 years) and nine older (66.2 ± 0.5 years), moderately active adults received primed continuous infusions of L-[ring-2H5]phenylalanine in basal and postprandial state. Blood and muscle biopsy samples were collected prior to and following ingestion of 25 g whey protein with or without knee extension exercise to examine skeletal muscle protein signalling and whole-body phenylalanine kinetics. Young adults had greater plasma IP6K1 at all time points. Older adults had reduced muscle IP6K1 at 120 min post-exercise. Muscle IP6K1 decreased 240 min postprandially in young adults compared with basal and there was no effect of exercise in either group. Older adults presented with reduced plasma and muscle IP6K1 in both postprandially and post-RE states, as well as reduced phenylalanine rate of disappearance for the same comparisons. IP6K1 may be involved in the reduction in amino acid metabolism, and the insulin-mediated response to protein and RE.

The online version contains supplementary material available at 10.1038/s41598-026-35711-2.