Intranasal insulin increases regional cerebral blood flow in the insular cortex in men independently of cortisol manipulation

Abstract

Insulin and cortisol play a key role in the regulation of energy homeostasis, appetite, and satiety. Little is known about the action and interaction of both hormones in brain structures controlling food intake and the processing of neurovisceral signals from the gastrointestinal tract. In this study, we assessed the impact of single and combined application of insulin and cortisol on resting regional cerebral blood flow (rCBF) in the insular cortex. After standardized periods of food restriction, 48 male volunteers were randomly assigned to receive either 40 IU intranasal insulin, 30 mg oral cortisol, both, or neither (placebo). Continuous arterial spin labeling (CASL) sequences were acquired before and after pharmacological treatment. We observed a bilateral, locally distinct rCBF increase after insulin administration in the insular cortex and the putamen. Insulin effects on rCBF were present regardless of whether participants had received cortisol or not. Our results indicate that insulin, but not cortisol, affects blood flow in human brain structures involved in the regulation of eating behavior.

Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums

“…Acute and chronic intranasal insulin administration improved memory and other cognitive functions in healthy adults with obesity or T2DM 114–123 , and neuroimaging studies found that intranasal insulin alters activation of cognitive brain regions and resting-state connectivity between the hippo campal region and the default-mode network 124–126 . Electrophysiology studies, including measurement of event-related potentials 127 , direct-current brain potentials 128 and magnetoencephalography 129,130 , also detected changes in response to acute intranasal insulin administration in healthy individuals and in people with obesity.…”

Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms

“…It is therefore important to characterize the specific dimensions of fatigue that develop in patient populations, and assess the role of inflammation. For instance, some aspects of fatigue may be derived from sleep alterations or changes in hormonal regulation in clinical populations, e.g., of insulin or cortisol, which can modulate brain functions including those in the above-mentioned areas (138–140). …”

Intranasal delivery: circumventing the iron curtain to treat neurological disorders

“…Recently, one group measured brain activity using positron emission tomography and found higher 18 F fluorodeoxyglucose uptake in the parietotemporal, frontal, precuneus and cuneus regions of the brain in patients receiving intranasal delivery of insulin [57]; however, the sample size was relatively small [58]. A recent systematic review [59] summarized that the underlying mechanism for intranasal delivery of insulin treating AD may be that this form of delivery could reverse brain atrophy, and bilateral, locally distinct regional cerebral blood flow (rCBF) was increased after insulin administration in the insular cortex and the putamen [59,60]. In addition, the neuroenergetic level was enhanced by intranasal insulin [61], and in turn, intrinsic brain activity was also increased in the hypothalamus and orbitofrontal cortex [62].…”