Release of insulin produced by the choroid plexis is regulated by serotonergic signaling

Mazucanti, Caio Henrique; Liu, Qingrong; Lang, Doyle; Huang, Nien-Tsu; O’Connell, Jennifer F.; Camandola, Simonetta; Egan, Josephine M.

doi:10.1172/jci.insight.131682

Cited by 68 publications

(55 citation statements)

References 73 publications

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“…Insulin secretion has also been reported in cultured astrocytes ( Takano et al, 2018 ). In a recent study, the authors describe the presence of not only insulin mRNA but also the protein itself in the epithelial layer of the choroid plexus of mice and humans, along with proteins associated with the processing and secretion of insulin ( Mazucanti et al, 2019 ).…”

Section: Metabolic Hallmarks Of Aging and Their Role In The Cognitivementioning

confidence: 99%

Inflamm-Aging and Brain Insulin Resistance: New Insights and Role of Life-style Strategies on Cognitive and Social Determinants in Aging and Neurodegeneration

et al. 2021

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Over the past decades, the human life span has dramatically increased, and therefore, a steady increase in diseases associated with age (such as Alzheimer’s disease and Parkinson’s disease) is expected. In these neurodegenerative diseases, there is a cognitive decline and memory loss, which accompany increased systemic inflammation, the inflamm-aging, and the insulin resistance. Despite numerous studies of age-related pathologies, data on the contribution of brain insulin resistance and innate immunity components to aging are insufficient. Recently, much research has been focused on the consequences of nutrients and adiposity- and nutrient-related signals in brain aging and cognitive decline. Moreover, given the role of metainflammation in neurodegeneration, lifestyle interventions such as calorie restriction may be an effective way to break the vicious cycle of metainflammation and have a role in social behavior. The various effects of calorie restriction on metainflammation, insulin resistance, and neurodegeneration have been described. Less attention has been paid to the social determinants of aging and the possible mechanism by which calorie restriction might influence social behavior. The purpose of this review is to discuss current knowledge in the interdisciplinary field of geroscience—immunosenescence, inflamm-aging, and metainflammation—which makes a significant contribution to aging. A substantial part of the review is devoted to frontiers in the brain insulin resistance in relation to neuroinflammation. In addition, we summarize new data on potential mechanisms of calorie restriction that influence as a lifestyle intervention on the social brain. This knowledge can be used to initiate successful aging and slow the onset of neurodegenerative diseases.

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Section: Metabolic Hallmarks Of Aging and Their Role In The Cognitivementioning

confidence: 99%

Inflamm-Aging and Brain Insulin Resistance: New Insights and Role of Life-style Strategies on Cognitive and Social Determinants in Aging and Neurodegeneration

et al. 2021

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“…The traditional view has been that CNS insulin is derived through the BBB, and that insulin is not synthesized in the CNS [ 34 , 35 ]. However, this view has been recently challenged [ 36 ], as some rodent [ 37 , 38 ] and human [ 39 ] studies have discovered insulin mRNA in the brain. In addition to being actively transported across the BBB, insulin also exhibits specific functions at the BBB via the insulin receptor, such as increasing the transport of leptin, tyrosine, and tryptophane from blood to the CNS [ 34 ].…”

Section: Transportation Of Glucose and Insulin Into The Brainmentioning

confidence: 99%

Brain Glucose Metabolism in Health, Obesity, and Cognitive Decline—Does Insulin Have Anything to Do with It? A Narrative Review

Rebelos

Rinne

Nuutila

2021

JCM

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Imaging brain glucose metabolism with fluorine-labelled fluorodeoxyglucose ([18F]-FDG) positron emission tomography (PET) has long been utilized to aid the diagnosis of memory disorders, in particular in differentiating Alzheimer’s disease (AD) from other neurological conditions causing cognitive decline. The interest for studying brain glucose metabolism in the context of metabolic disorders has arisen more recently. Obesity and type 2 diabetes—two diseases characterized by systemic insulin resistance—are associated with an increased risk for AD. Along with the well-defined patterns of fasting [18F]-FDG-PET changes that occur in AD, recent evidence has shown alterations in fasting and insulin-stimulated brain glucose metabolism also in obesity and systemic insulin resistance. Thus, it is important to clarify whether changes in brain glucose metabolism are just an epiphenomenon of the pathophysiology of the metabolic and neurologic disorders, or a crucial determinant of their pathophysiologic cascade. In this review, we discuss the current knowledge regarding alterations in brain glucose metabolism, studied with [18F]-FDG-PET from metabolic disorders to AD, with a special focus on how manipulation of insulin levels affects brain glucose metabolism in health and in systemic insulin resistance. A better understanding of alterations in brain glucose metabolism in health, obesity, and neurodegeneration, and the relationships between insulin resistance and central nervous system glucose metabolism may be an important step for the battle against metabolic and cognitive disorders.

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“…Accordingly, a recent study reports that the IR antagonist S-961 blunted insulin uptake in a brain endothelial cell culture, 53 whereas another study shows that the same antagonist slightly reduces insulin transport to the mouse brain suggesting that insulin transport can occur independently of its receptor. 54 Interestingly, recent evidence demonstrates that insulin can be directly produced by choroid plexi 55 and might be provided to brain structures closed to the ventricles.…”

Section: Overview Of Brain Insulin Signallingmentioning

confidence: 99%

The impact of insulin on the serotonergic system and consequences on diabetes‐associated mood disorders

Martin

Bullich

Guiard

et al. 2021

J Neuroendocrinology

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The idea that insulin could influence emotional behaviours has long been suggested.However, the underlying mechanisms have yet to be solved and there is no direct and clear-cut evidence demonstrating that such action involves brain serotonergic neurones. Indeed, initial arguments in favour of the association between insulin, serotonin and mood arise from clinical or animal studies showing that impaired insulin action in type 1 or type 2 diabetes causes anxiety-and depressive symptoms along with blunted plasma and brain serotonin levels. The present review synthesises the main mechanistic hypotheses that might explain the comorbidity between diabetes and depression. It also provides a state of knowledge of the direct and indirect experimental evidence that insulin modulates brain serotonergic neurones. Finally, it highlights the literature suggesting that antidiabetic drugs present antidepressantlike effects and, conversely, that serotonergic antidepressants impact glucose homeostasis. Overall, this review provides mechanistic insights into how insulin signalling alters serotonergic neurotransmission and related behaviours bringing new targets for therapeutic options.

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Release of insulin produced by the choroid plexis is regulated by serotonergic signaling

Cited by 68 publications

References 73 publications

Inflamm-Aging and Brain Insulin Resistance: New Insights and Role of Life-style Strategies on Cognitive and Social Determinants in Aging and Neurodegeneration

Inflamm-Aging and Brain Insulin Resistance: New Insights and Role of Life-style Strategies on Cognitive and Social Determinants in Aging and Neurodegeneration

Brain Glucose Metabolism in Health, Obesity, and Cognitive Decline—Does Insulin Have Anything to Do with It? A Narrative Review

The impact of insulin on the serotonergic system and consequences on diabetes‐associated mood disorders

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