Peripheral versus central insulin and leptin resistance: Role in metabolic disorders, cognition, and neuropsychiatric diseases.

Insulin and leptin are classically regarded as peptide hormones that play key roles in metabolism. In actuality, they serve several functions in both the periphery and central nervous system (CNS). Likewise, insulin and leptin resistance can occur both peripherally and centrally. Metabolic disorders such as diabetes and obesity share several key features including insulin and leptin resistance. While the peripheral effects of these disorders are well-known (i.e. cardiovascular disease, hypertension, stroke, dyslipidemia, etc.), the CNS complications of leptin and insulin resistance have come into sharper focus. Both preclinical and clinical findings have indicated that insulin and leptin resistance are associated with cognitive deficits and neuropsychiatric diseases such as depression. Importantly, these studies also suggest that these deficits in neuroplasticity can be reversed by restoration of insulin and leptin sensitivity. In view of these observations, this review will describe, in detail, the peripheral and central functions of insulin and leptin and explain the role of insulin and leptin resistance in various metabolic disorders, cognition, and neuropsychiatric diseases.

Intranasal insulin and orexins to treat age-related cognitive decline.

The intranasal (IN) administration of neuropeptides, such as insulin and orexins, has been suggested as a treatment strategy for age-related cognitive decline (ARCD). Because dysfunctional neuropeptide signaling is an observed characteristic of ARCD, it has been suggested that IN delivery of insulin and/or orexins may restore endogenous peptide signaling and thereby preserve cognition. IN administration is particularly alluring as it is a relatively non-invasive method that directly targets peptides to the brain. Several laboratories have examined the behavioral effects of IN insulin in young, aged, and cognitively impaired rodents and humans. These studies demonstrated improved performance on various cognitive tasks following IN insulin administration. Fewer laboratories have assessed the effects of IN orexins; however, this peptide also holds promise as an effective treatment for ARCD through the activation of the cholinergic system and/or the reduction of neuroinflammation. Here, we provide a brief overview of the advantages of IN administration and the delivery pathway, then summarize the current literature on IN insulin and orexins. Additional preclinical studies will be useful to ultimately uncover the mechanisms underlying the pro-cognitive effects of IN insulin and orexins, whereas future clinical studies will aid in the determination of the most efficacious dose and dosing paradigm. Eventually, IN insulin and/or orexin administration may be a widely used treatment strategy in the clinic for ARCD.

Ratings of Perceived Exertion and Physiological Responses in Children During Exercise.

OMNI ratings of perceived exertion (RPE) and physiological responses in children (n=7 boys, 8 girls, 11.1±1.0 years) were examined during estimation (graded exercise test [GXT] and steady-state) and production (steady-state) trials on a cycle ergometer. Peak oxygen consumption (VO2peak) was determined via a GXT with RPE estimated every 30 s. Later, two 6-min trials were completed: Participants 1) estimated RPE at ~75% of VO2peak, 2) produced a level of exertion corresponding to their RPE at ~75% of VO2peak during the GXT. Data analysis included a one-way MANOVA and a paired t-test. The target intensity during the GXT corresponded to 74.2±2.5% of VO2peak; the steady-state estimation and production trials were performed at 76.5±2.7% and 68.5±14.1% of VO2peak, respectively (p>0.05). Mean RPE at ~75% of VO2peak during the GXT and production trial was 6.7±1.5; during the steady-state estimation trial RPE was 5.8±2.0 (p>0.05). There were no differences (p>0.05) in the physiological responses. Participants estimated RPE similarly at ~75% of VO2peak during both graded and steady-state exercise, but when asked to produce a given RPE, marked variability was observed in physiological responses. These findings may have implications in optimizing exercise prescriptions for children.