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

Richie D Barclay; Diana E Motei; Oana Ancu; Christopher J Tyler; Neale A Tillin; Volker Behrends; Nicholas A Burd; Nicholas M Hurren; Richard W A Mackenzie

doi:10.1038/s41598-026-35711-2

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

Richie D Barclay
, Diana E Motei
, Oana Ancu
, Christopher J Tyler
, Neale A Tillin
, Volker Behrends
, Nicholas A Burd
, Nicholas M Hurren
, Richard W A Mackenzie

University of Roehampton
University of West London
University of Illinois at Urbana-Champaign
University Hospitals Coventry and Warwickshire NHS Trust
VisitHealth

Research output: Contribution to journal › Article › peer-review

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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- H ]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. [Abstract copyright: © 2026. Crown.]

Original language	English
Article number	9490
Number of pages	13
Journal	Scientific Reports
Volume	16
Issue number	1
Early online date	18 Feb 2026
DOIs	https://doi.org/10.1038/s41598-026-35711-2
Publication status	E-pub ahead of print - 18 Feb 2026

Bibliographical note

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and
indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Ageing
Metabolism
IP6K1
Amino acids
Resistance exercise
Insulin resistance

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title = "Inositol hexakisphosphate kinase 1 is implicated in the insulin response to protein ingestion 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- H ]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. [Abstract copyright: {\textcopyright} 2026. Crown.]",

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AU - Behrends, Volker

AU - Burd, Nicholas A

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N2 - 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- H ]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. [Abstract copyright: © 2026. Crown.]

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KW - IP6K1

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KW - Resistance exercise

KW - Insulin resistance

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JF - Scientific Reports

IS - 1

M1 - 9490

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

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