Untangling the effect of insulin action on brain mitochondria and metabolism

Schell, Mareike; Wardelmann, Kristina; Kleinridders, André

doi:10.1111/jne.12932

Cited by 31 publications

(32 citation statements)

References 131 publications

(156 reference statements)

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“…Thus, functional neuronal insulin/IGF1-1 signaling is essential for healthy metabolism in the brain and is closely related to mitochondrial energy homeostasis [ 136 ]. In agreement with these findings, activation of the insulin/IGF-1 pathway improves mitochondrial respiration, ATP production, AMPK activation, Ca 2+ buffering, and increased PGC1α expression, revealing the importance of the interplay between mitochondrial function and insulin/IGF-1 action to maintain brain activity [ 136 ].…”

Section: Insulin Insulin Resistance and Mitochondrial Dysfunctionmentioning

confidence: 99%

“…Insulin can act on astrocytes and glial cells, influencing their metabolism. In glial cells, in fact, insulin, by binding to its receptor, activates the IRS-1/PI3K/Akt signaling that stimulates phagocytic action and proinflammatory activity of microglia and influences the mitochondrial production of ATP [ 136 ]. In mice, a high-calorie diet induces, in proopiomelanocortin (POMC) neurons, activation of microglia, which produces TNFα and stimulates mitochondrial ATP production.…”

Section: Insulin Insulin Resistance and Mitochondrial Dysfunctionmentioning

confidence: 99%

“…Furthermore, several reports indicate that chronic high-fat feeding (HFD) causes insulin resistance in brain mice. Indeed, in the hypothalamus of HFD mice, the association of insulin resistance to dysregulated mitochondrial homeostasis was demonstrated by altered morphology, decreased mitochondrial respiration, and reduced mitochondrial-endoplasmic-reticulum contact sites, and disturbances in the quality and number of mitochondria [ 136 ]. Moreover, our studies using the same animal model showed an alteration in the mitophagic process in a time-dependent manner associated with the condition of insulin resistance [ 145 ].…”

Section: Insulin Insulin Resistance and Mitochondrial Dysfunctionmentioning

confidence: 99%

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Insulin and Its Key Role for Mitochondrial Function/Dysfunction and Quality Control: A Shared Link between Dysmetabolism and Neurodegeneration

Galizzi

Carlo

2022

Biology

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This review will comprise an overview of insulin and its history, structure, synthesis, secretion, signaling, and peripheral and brain roles. Further, the impact that metabolic diseases and the insulin resistance (IR) condition can exert on brain function will be surveyed. Later, attention will be given to the complex relation of mitochondrial dysfunction, brain insulin resistance, and neurodegenerative disease, especially Alzheimer’s disease (AD). We will also focus our consideration on the role played by insulin or the IR condition in mitochondrial homeostasis by analyzing the different processes involved in the quality control of mitochondria (MQC), such as mitochondrial dynamics, mitochondrial biogenesis, and selective autophagy (mitophagy), as well as pathophysiological implications of these aspects. Finally, the possibility of employing the mitochondrion as a target to fight dysmetabolism and AD-related effects will also be reviewed.Abstract: Insulin was discovered and isolated from the beta cells of pancreatic islets of dogs and is associated with the regulation of peripheral glucose homeostasis. Insulin produced in the brain is related to synaptic plasticity and memory. Defective insulin signaling plays a role in brain dysfunction, such as neurodegenerative disease. Growing evidence suggests a link between metabolic disorders, such as diabetes and obesity, and neurodegenerative diseases, especially Alzheimer’s disease (AD). This association is due to a common state of insulin resistance (IR) and mitochondrial dysfunction. This review takes a journey into the past to summarize what was known about the physiological and pathological role of insulin in peripheral tissues and the brain. Then, it will land in the present to analyze the insulin role on mitochondrial health and the effects on insulin resistance and neurodegenerative diseases that are IR-dependent. Specifically, we will focus our attention on the quality control of mitochondria (MQC), such as mitochondrial dynamics, mitochondrial biogenesis, and selective autophagy (mitophagy), in healthy and altered cases. Finally, this review will be projected toward the future by examining the most promising treatments that target the mitochondria to cure neurodegenerative diseases associated with metabolic disorders.

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Section: Insulin Insulin Resistance and Mitochondrial Dysfunctionmentioning

confidence: 99%

Section: Insulin Insulin Resistance and Mitochondrial Dysfunctionmentioning

confidence: 99%

Section: Insulin Insulin Resistance and Mitochondrial Dysfunctionmentioning

confidence: 99%

See 1 more Smart Citation

Insulin and Its Key Role for Mitochondrial Function/Dysfunction and Quality Control: A Shared Link between Dysmetabolism and Neurodegeneration

Galizzi

Carlo

2022

Biology

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“…On the other hand, there is also much evidence that insulin and IGF-1 directly influence OXPHOS efficiency and mitochondrial stability in the brain. In numerous in vitro studies conducted on neuronal and glial cell lines and primary cultures, stimulation with insulin or IGF-1 improved mitochondrial respiration, upregulated the expression of mitochondrial complexes and increased ATP production [ 30 , 31 , 32 ]. Similar results were also observed in in vivo experiments, and most of the current data concerning the direct central action of insulin energy metabolism and mitochondrial function come from experiments with intranasal administration of insulin, which enables us to study its direct action in the brain and omit peripheral effects of this hormone.…”

Section: Glucoregulatory Hormones Affect Energy Homeostasis and Mitochondrial Function In The Brainmentioning

confidence: 99%

Hormonal Regulation of Oxidative Phosphorylation in the Brain in Health and Disease

Głombik

Detka

Budziszewska

2021

Cells

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The developing and adult brain is a target organ for the vast majority of hormones produced by the body, which are able to cross the blood–brain barrier and bind to their specific receptors on neurons and glial cells. Hormones ensure proper communication between the brain and the body by activating adaptive mechanisms necessary to withstand and react to changes in internal and external conditions by regulating neuronal and synaptic plasticity, neurogenesis and metabolic activity of the brain. The influence of hormones on energy metabolism and mitochondrial function in the brain has gained much attention since mitochondrial dysfunctions are observed in many different pathological conditions of the central nervous system. Moreover, excess or deficiency of hormones is associated with cell damage and loss of function in mitochondria. This review aims to expound on the impact of hormones (GLP-1, insulin, thyroid hormones, glucocorticoids) on metabolic processes in the brain with special emphasis on oxidative phosphorylation dysregulation, which may contribute to the formation of pathological changes. Since the brain concentrations of sex hormones and neurosteroids decrease with age as well as in neurodegenerative diseases, in parallel with the occurrence of mitochondrial dysfunction and the weakening of cognitive functions, their beneficial effects on oxidative phosphorylation and expression of antioxidant enzymes are also discussed.

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“…In addition, cognitive disorders raise significant financial concerns [1,[31][32][33][34]. Greater than 800 billion United States dollars (USD) per year are required to treat dementia equaling approximately 2 percent of the global Gross Domestic Product.…”

Section: Introductionmentioning

confidence: 99%

Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm

Maiese

2021

Front Biosci (Landmark Ed)

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Introduction 3. Biological clocks and circadian rhythm pathways for dementia treatment 4. Circadian rhythm disruption and the wingless wnt pathway 5. The mechanistic target of rapamycin (mTOR) and autophagy 6. The silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) 7. Mammalian forkhead transcription factors (FoxOs) 8. Future perspectives 9. Author contributions 10. Ethics approval and consent to participate 11. Acknowledgment 12. Funding 13. Conflict of interest 14. References

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Untangling the effect of insulin action on brain mitochondria and metabolism

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 31 publications

References 131 publications

Insulin and Its Key Role for Mitochondrial Function/Dysfunction and Quality Control: A Shared Link between Dysmetabolism and Neurodegeneration

Insulin and Its Key Role for Mitochondrial Function/Dysfunction and Quality Control: A Shared Link between Dysmetabolism and Neurodegeneration

Hormonal Regulation of Oxidative Phosphorylation in the Brain in Health and Disease

Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm

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