Abstract
Exercise provides a therapeutic pathways to mitigate cognitive decrements through benefits to cerebrovascular and neurological function. Intranasal delivery of insulin also offers a therapeutic pathway, possibly via enhancing cerebral metabolism. We assessed cerebral oxygen and glucose metabolism (CMRO2 and CMRglc, respectively) via cross-brain blood sampling and ultrasound measurement of cerebral blood flow (CBF), following two successive intranasal insulin (INI) administrations (52 IU); once at rest, and again at rest but following 1 h of prolonged cycling exercise. Measurement timepoints following both INI administration were 5, 10, 15, 20, 30, 45, and 60 min post. Eleven healthy young adults (5 female, 22.4 ± 1.7 kg/m2) completed this protocol, and, between INI bouts, completed cycling exercise, consisting of 2-3 one-minute bouts at 80%-100% of work rate max followed by 90 min at 90% of lactate threshold (~2 h total). At rest, INI had no effect on CMRO2 (p = 0.141) while CMRglc may have been elevated (p = 0.086). Comparing the effects of INI pre- and post-exercise, CMRO2 was not different (condition, p = 0.333). Collapsing both conditions (pre- and post-exercise) CMRO2 was increased from baseline at 30 min (time, p = 0.007). CMRglc was also not different between conditions (condition, p = 0.498), but was increased (time, p < 0.001) from baseline (0.34 ± 0.02 mmol/min) to 45 min (0.40 ± 0.02 mmol/min) by 20% ± 28% (p = 0.017) across both conditions. Whole brain cerebral metabolism sensitivity to intranasal insulin is minimal at rest, but seems to be increased following exercise, likely due to exercise induced hypoglycaemia driving a supercompensatory response. These findings provide mechanistic support for the cognitive benefits of exercise, and potentially intranasal insulin, through enhanced cerebral metabolism.