Intranasal insulin attenuates the hypothalamic–pituitary–adrenal axis response to psychosocial stress

Böhringer, Andreas; Schwabe, Lars; Richter, Steffen; Schächinger, Hartmut

doi:10.1016/j.psyneuen.2008.08.002

Cited by 71 publications

(48 citation statements)

References 35 publications

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“…However, cortisol levels were not affected by the application of nasal insulin. By contrast, Bohringer et al [45] found the cortisol response to psychosocial stress to be reduced by nasal insulin. Thus, a stress-induced increase in activity of the HPA axis may be a response to high insulin levels in the brain, while in a non-stressed milieu (as in our experiment) this neuroendocrine system is not affected.…”

Section: Discussionmentioning

confidence: 89%

Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions

et al. 2012

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Aims/hypothesis Impaired insulin sensitivity is a major factor leading to type 2 diabetes. Animal studies suggest that the brain is involved in the regulation of insulin sensitivity. We investigated whether insulin action in the human brain regulates peripheral insulin sensitivity and examined which brain areas are involved. Methods Insulin and placebo were given intranasally. Plasma glucose, insulin and C-peptide were measured in 103 participants at 0, 30 and 60 min. A subgroup (n012) was also studied with functional MRI, and blood sampling at 0, 30 and 120 min. For each time-point, the HOMA of insulin resistance (HOMA-IR) was calculated as an inverse estimate of peripheral insulin sensitivity.

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Section: Discussionmentioning

confidence: 89%

Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions

et al. 2012

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“…However, in pilot experiments in obese men, 8 weeks of intranasal insulin treatment had no effect on body weight and body fat mass [18]. Nevertheless, insulin administration improved declarative memory functions and reduced HPA axis secretory activity, effects that resemble those observed in normal-weight participants [20,25]. This pattern suggests that in obese patients, brain structures involved in energy homeostasis show decreased sensitivity to the effects of insulin.…”

Section: Central Nervous Insulin Resistancementioning

confidence: 94%

“…infusion of the hormone is severely limited by the emergence of strong systemic side effects mainly on blood glucose concentrations and by the constraints of BBB transport [2]. Intranasal insulin administration bypasses uptake into the bloodstream and allows direct access to the cerebrospinal fluid (CSF) compartment within 30 min [15] without relevant changes in blood glucose and serum insulin levels [15][16][17][18][19][20]. Intranasally administered peptides may reach the brain along olfactory but also trigeminal pathways [21].…”

Section: Central Nervous Insulin Effects In Healthy Humansmentioning

confidence: 99%

“…Thus intranasal insulin administration to increase central nervous availability of the hormone, although apparently ineffective in reducing body weight in the obese state [18], reduces HPA axis activity [18,20,25] and may thus counteract the development of visceral obesity, as well as cognitive impairments assumed to be promoted by excessive HPA axis secretion related to chronic stress. Likewise, boosting hypothalamic insulin signalling may help normalise dysregulated hepatic gluconeogenesis [7], a hallmark of type 2 diabetes and peripheral insulin resistance [34], which appears to be highly associated with central nervous insulin resistance [39].…”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

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Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

Hallschmid

Schultes

2009

Diabetologia

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Research on functions and signalling pathways of insulin has traditionally focused on peripheral tissues such as muscle, fat and liver, while the brain was commonly believed to be insensitive to the effects of this hormone secreted by pancreatic beta cells. However, since the discovery some 30 years ago that insulin receptors are ubiquitously found in the central nervous system, an evergrowing research effort has conclusively shown that circulating insulin accesses the brain, which itself does not synthesise insulin, and exerts pivotal functions in central nervous networks. As an adiposity signal reflecting the amount of body fat, insulin provides direct negative feedback to hypothalamic nuclei that control whole-body energy and glucose homeostasis. Moreover, insulin affects distinct cognitive processes, e.g. by triggering the formation of psychological memory contents. Accordingly, metabolic and cognitive disorders such as obesity, type 2 diabetes mellitus and Alzheimer's disease are associated with resistance of central nervous structures to the effects of insulin, which may derive from genetic polymorphisms as well as from long-term exposure to excess amounts of circulating insulin due to peripheral insulin resistance. Thus, overcoming central nervous insulin resistance, e.g. by pharmacological interventions, appears to be an attractive strategy in the treatment and prevention of these disorders. Enhancement of central nervous insulin signalling by administration of intranasal insulin, insulin analogues and insulin sensitisers in basic research approaches has yielded encouraging results that bode well for the successful translation of these effects into future clinical practice.

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“…Previous studies have also revealed that obesity-dependent deficits in cognition predominantly involved executive functions [35,36]. It has been shown that insulin increases memory, probably by binding to receptors in the hippocampus and the limbic part of the brain [37], while other studies show that insulin administration improves memory functions in non-obese patients [38,39]. However, in obese patients, insulin sensitivity is reduced and the resulting impairment in vocabulary memory can lead to verbal disabilities.…”

Section: Discussionmentioning

confidence: 99%

Relation of insulin resistance to neurocognitive function and electroencephalography in obese children

Akın

Eker

Arslan

et al. 2017

Journal of Pediatric Endocrinology and Metabolism

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Background: Childhood obesity may lead to neuronal impairment in both the peripheral and the central nervous system. This study aimed to investigate the impact of obesity and insulin resistance (IR) on the central nervous system and neurocognitive functions in children. Methods: Seventy-three obese children (38 male and 35 female) and 42 healthy children (21 male and 21 female) were recruited. Standard biochemical indices and IR were evaluated. The Wechsler Intelligence Scale for Children-Revised (WISC-R) and electroencephalography (EEG) were administered to all participants. The obese participants were divided into two groups based on the presence or absence of IR, and the data were compared between the subgroups. Results: Only verbal scores on the WISC-R in the IR+ group were significantly lower than those of the control and IRgroups. There were no differences between the groups with respect to other parameters of the WISC-R or the EEG. Verbal scores of the WISC-R were negatively correlated with obesity duration and homeostatic model assessmentinsulin resistance (HOMA-IR) values. EEGs showed significantly more frequent 'slowing during hyperventilation' (SDHs) in obese children than non-obese children.

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Intranasal insulin attenuates the hypothalamic–pituitary–adrenal axis response to psychosocial stress

Cited by 71 publications

References 35 publications

Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions

Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions

Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

Relation of insulin resistance to neurocognitive function and electroencephalography in obese children

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