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

Young adults had greater plasma IP6K1 concentrations than older adults at all time points measured.

• Nine young adults (24.9 ± 0.4 years) and nine older adults (66.2 ± 0.5 years) were compared.
• Both groups were described as moderately active.
• Plasma IP6K1 was greater in young adults across all time points including basal and postprandial states.
• The difference in plasma IP6K1 persisted regardless of whether protein ingestion was combined with resistance exercise.

Older adults had reduced muscle IP6K1 at 120 minutes post-exercise.

• Muscle biopsies were collected prior to and following ingestion of 25 g whey protein with or without knee extension exercise.
• The reduction in muscle IP6K1 was observed specifically at the 120-minute post-exercise time point in older adults.
• No effect of exercise on muscle IP6K1 was observed in either young or older adults more broadly.

Muscle IP6K1 decreased 240 minutes postprandially in young adults compared with basal conditions.

• The decrease in muscle IP6K1 was observed at 240 minutes following protein ingestion in young adults.
• No corresponding postprandial decrease in muscle IP6K1 was reported for older adults at this time point.
• There was no effect of exercise on muscle IP6K1 in either group.

Older adults presented with reduced plasma and muscle IP6K1 in both postprandial and post-resistance exercise states.

• Reductions were observed in both the protein-only and protein plus resistance exercise conditions.
• Reduced IP6K1 in older adults was seen in both plasma and muscle tissue compartments.
• This pattern was concurrent with reduced phenylalanine rate of disappearance in older adults under the same conditions.

Older adults had reduced phenylalanine rate of disappearance in both postprandial and post-resistance exercise states.

• Whole-body phenylalanine kinetics were assessed using primed continuous infusions of L-[ring-2H5]phenylalanine.
• Blood and muscle biopsy samples were collected in basal and postprandial states.
• Reduced phenylalanine rate of disappearance in older adults paralleled their reductions in plasma and muscle IP6K1.
• Phenylalanine rate of disappearance was reduced in older adults for both the protein ingestion alone and protein plus resistance exercise comparisons.

IP6K1 has been previously shown to inhibit Akt-mTORC1 signalling in pre-diabetic humans, providing a mechanistic basis for its role in age-related anabolic resistance.

• Insulin activates Akt-mTORC1 signalling in skeletal muscle.
• IP6K1 (inositol hexakisphosphate kinase 1) was previously identified as an inhibitor of this signalling pathway in pre-diabetic humans.
• Age-related muscle mass loss is partly mediated by a reduction in insulin sensitivity and reduced amino acid and anabolic signalling kinetics.
• The authors propose that IP6K1 may be involved in the insulin-mediated response to protein ingestion and resistance exercise.

The study used a within-subject design with stable isotope tracer infusions and repeated muscle biopsies to assess protein signalling and whole-body phenylalanine kinetics.

• Primed continuous infusions of L-[ring-2H5]phenylalanine were used in both basal and postprandial states.
• Participants ingested 25 g whey protein with or without knee extension exercise.
• Blood and muscle biopsy samples were collected prior to and following the interventions.
• Nine young (24.9 ± 0.4 years) and nine older (66.2 ± 0.5 years) moderately active adults were enrolled.