Insulin gene expression and insulin synthesis in mammalian neuronal cells.

Devaskar, Sherin U.; Giddings, Stephen J.; Rajakumar, Premeela A.; Carnaghi, Lynn R.; Menon, Ram K.; Zahm, Daniel S.

doi:10.1016/s0021-9258(17)37214-9

Cited by 293 publications

(27 citation statements)

References 36 publications

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“…Humans and rabbits have a single gene encoding for insulin, while rodents have two. Of the two Ins genes that lead to the production of preproinsulin in rodents, Ins II appears to be the one predominantly expressed by neurons [ 17 , 18 ]. In cultured rabbit neurons and glia, only neurons can secrete insulin into culture media [ 18 ].…”

Section: Insulin Receptor Expression and Signaling In The Brainmentioning

confidence: 99%

“…Of the two Ins genes that lead to the production of preproinsulin in rodents, Ins II appears to be the one predominantly expressed by neurons [ 17 , 18 ]. In cultured rabbit neurons and glia, only neurons can secrete insulin into culture media [ 18 ]. While Ins II may be expressed in the brain in vivo, whether the endopeptidases that are required for secretion of the mature hormone product are expressed in the brain has been less well-demonstrated.…”

Section: Insulin Receptor Expression and Signaling In The Brainmentioning

confidence: 99%

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The brain as an insulin-sensitive metabolic organ

Milstein

Ferris

2021

Molecular Metabolism

128

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Background The brain was once thought of as an insulin-insensitive organ. We now know that the insulin receptor is present throughout the brain and serves important functions in whole-body metabolism and brain function. Brain insulin signaling is involved not only in brain homeostatic processes but also neuropathological processes such as cognitive decline and Alzheimer's disease. Scope of review In this review, we provide an overview of insulin signaling within the brain and the metabolic impact of brain insulin resistance and discuss Alzheimer's disease, one of the neurologic diseases most closely associated with brain insulin resistance. Major conclusions While brain insulin signaling plays only a small role in central nervous system glucose regulation, it has a significant impact on the brain's metabolic health. Normal insulin signaling is important for mitochondrial functioning and normal food intake. Brain insulin resistance contributes to obesity and may also play an important role in neurodegeneration.

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Section: Insulin Receptor Expression and Signaling In The Brainmentioning

confidence: 99%

Section: Insulin Receptor Expression and Signaling In The Brainmentioning

confidence: 99%

The brain as an insulin-sensitive metabolic organ

Milstein

Ferris

2021

Molecular Metabolism

128

View full text Add to dashboard Cite

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“…The high levels of insulin in brain extracts, however, pointed towards the de novo synthesis of insulin in the CNS [15]. This was supported by the detection of insulin secretion in neuronal cultures [21], and the presence of insulin immunoreaction within the Golgi and the rough endoplasmic reticulum in the brain [22]. Insulin 2 mRNA was also identified in GABAergic neurogliaform cells in the cerebral cortex of the rat [23] and preproinsulin mRNA was found in rat retinal tissue [24].…”

Section: Insulin Signaling In the Cns And Retinamentioning

confidence: 99%

Insulin Signaling as a Therapeutic Target in Glaucomatous Neurodegeneration

Wareham

Risner

Calkins

2021

IJMS

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Glaucoma is a multifactorial disease that is conventionally managed with treatments to lower intraocular pressure (IOP). Despite these efforts, many patients continue to lose their vision. The degeneration of retinal ganglion cells (RGCs) and their axons in the optic tract that characterizes glaucoma is similar to neurodegeneration in other age-related disorders of the central nervous system (CNS). Identifying the different molecular signaling pathways that contribute to early neuronal dysfunction can be utilized for neuroprotective strategies that prevent degeneration. The discovery of insulin and its receptor in the CNS and retina led to exploration of the role of insulin signaling in the CNS. Historically, insulin was considered a peripherally secreted hormone that regulated glucose homeostasis, with no obvious roles in the CNS. However, a growing number of pre-clinical and clinical studies have demonstrated the potential of modulating insulin signaling in the treatment of neurodegenerative diseases. This review will highlight the role that insulin signaling plays in RGC neurodegeneration. We will focus on how this pathway can be therapeutically targeted to promote RGC axon survival and preserve vision.

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“…Insulin can be delivered to the CNS via circulation and transport across the BBB [137]. However, insulin transcription has also been detected in neural and glial cultures, suggesting that insulin can act in both an endocrine and paracrine fashion on CNS cells [138,139]. Insulin binds to the insulin receptor (IR), a cell surface receptor with tyrosine kinase activity that, in the CNS, is expressed in the olfactory bulbs, the arcuate nucleus of the hypothalamus, and the hippocampus [140].…”

Section: Insulinmentioning

confidence: 99%

Hormonal Regulation of Oligodendrogenesis I: Effects across the Lifespan

Long¹,

Breton²,

Barraza³

et al. 2021

Preprint

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The brain’s capacity to respond to changing environments via hormonal signaling is critical to fine-tuned function. An emerging body of literature highlights a role for myelin plasticity as a prominent type of experience-dependent plasticity in the adult brain. Myelin plasticity is driven by oligodendrocytes (OLs) and their precursor cells (OPCs). OPC differentiation regulates the trajectory of myelin production throughout development, and importantly, OPCs maintain the ability to proliferate and generate new OLs throughout adulthood. The process of oligodendrogenesis (OLgenesis), the creation of new OLs, can be dramatically influenced during early development and in adulthood by internal and environmental conditions such as hormones. Here, we review the current literature describing hormonal regulation of OLgenesis within physiological conditions, focusing on several classes of hormones: steroid, peptide, and thyroid hormones. We discuss hormonal regulation at each stage of OLgenesis and describe mechanisms of action, where known. Overall, the majority of hormones enhance OLgenesis, increasing OPC differentiation and inducing maturation and myelin production in OLs. The mechanisms underlying these processes vary for each hormone but may ultimately converge upon common signaling pathways, mediated by specific receptors expressed across the OL lineage. However, not all of the mechanisms have been fully elucidated, and here, we note the remaining gaps in the literature, including the complex interactions between hormonal systems and with the immune system. In the companion manuscript in this issue [1], we discuss the implications of hormonal regulation of OLgenesis for neurological and psychiatric disorders characterized by white matter loss. Ultimately, a better understanding of the fundamental mechanisms of hormonal regulation of OLgenesis across the entire lifespan, especially in vivo, will progress both basic and translational research.

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Insulin gene expression and insulin synthesis in mammalian neuronal cells.

Cited by 293 publications

References 36 publications

The brain as an insulin-sensitive metabolic organ

The brain as an insulin-sensitive metabolic organ

Insulin Signaling as a Therapeutic Target in Glaucomatous Neurodegeneration

Hormonal Regulation of Oligodendrogenesis I: Effects across the Lifespan

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