The cellular and physiological actions of insulin in the central nervous system

doi:10.1016/0197-0186(93)90062-A

Neurochemistry International

Volume 22, Issue 1, January 1993, Pages 1-10

https://doi.org/10.1016/0197-0186(93)90062-A Get rights and content

Abstract

Insulin is a peptide hormone involved in the regulation of glucose homeostasis. Its synthesis and function in the peripheral tissues have been extensively studied and well understood. In contrast, demonstration of insulin in the brain has raised questions concerning its origin and physiological significance. In spite of extensive studies, the source of insulin present in the brain has not yet been conclusively identified. Evidence exists in support of both peripheral and central origins of this hormone in the brain. Recognized physiological effects of insulin in the central nervous system (CNS) include regulation of food intake, control of glucose uptake and trophic actions on neuronal and glial cells. These actions of insulin are mediated by insulin receptor resembling closely that in peripheral tissues and coupled with tyrosine kinase signal transduction pathway. In this review we will discuss theories concerning the origin of insulin in the CNS. In addition, we will present current information on both cellular and physiological effects of this hormone in the brain.

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Citation Excerpt :
Indeed, IR mRNA and immunoreactive insulin are defined within the endoplasmic reticulum, Golgi apparatus, cytoplasm, axon, dendrites, and the synapses in the brain [30,31]. In addition to peripheral insulin crossing the BBB, a smaller amount of insulin could be synthesized de novo in the brain, and insulin signal is perceived by IR resembling strongly the one in peripheral tissues and coupled with tyrosine kinase signal transduction pathway [32]. Besides being the master regulator of brain glucose metabolism, insulin is a major neuromodulator that takes part in various neurobiological mechanisms especially in neuronal growth, energy homeostasis, and cognition.
Environmental bisphenol A (BPA) exposure and bioaccumulation are higher than expected levels. In the long run, continuing BPA exposure impairs synaptic transmission and contributes to BPA-induced cognitive impairment, while increasing type 2 diabetes risk via promoting pancreatic β-cell death. BPA-insulin-Alzheimer’s disease (AD) axis represents a neuro-endocrine disorder and is termed as “Type 3 Diabetes”. BPA elevates oxidative stress and amyloid-beta accumulation in the AD brain, while increasing neuroinflammation and tau-phosphorylation. Neuronal viability is protected at high glucose concentration and insulin resistance conditions by N-methyl-d-aspartate (NMDA) receptor antagonists. Interestingly, despite its NMDA receptor suppressive effect, BPA contributes to neurotoxicity. Conversely, improvement of NMDA receptor functions shows protective effects against BPA-induced neurotoxicity. Thus, the mechanism of BPA neurotoxicity remains to be clarified.
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CommentaryThe cellular and physiological actions of insulin in the central nervous system

Abstract

Brain Res.

Life Sci.

Devl. Brain Res.

Brain Res.

Brain Res.

Adv. Metab. Disorders

Structural differences between insulin receptors in the brain and peripheral target tissues

Neuroscience

Appetite

Biochem. biophys. Res.

Brain Res.

Int. J. Biochem.

Brain Res.

J. biol. Chem.

Exp. Cell Res.

Brain Res.

Neurochem. Int.

Neuroscience

Adv. metab. Disorders

Am. J. Clin. Nutr.

Adv. metab. Disorders

Neuropeptides

Neuropeptides

Characterization of beta adrenergic receptors from neuronal and glial cells in primary cultures of rat brain

J. Neurochem.

Regional concentrations of insulin in the rat brain

Endocrinology

Quantitative autoradiographic evidence for insulin receptors in the choroid plexus of the rat brain

Diabetes

Development of receptors for insulin and insulin-like growth factor-I in head and brain of chick embryos: autoradiographic localization

Endocrinology

Immunoreactive insulin from mouse brain cells in culture and from whole brain

J. Biochem.

Effects of insulin and tunicamycin on neuronal insulin receptors in culture

Am. J. Physiol.

Insulin receptors and insulin modulation of norepinephrine uptake in neuronal cultures from rat brain

J. biol. Chem.

Insulin receptor kinase is hyperresponsive in adipocytes of young Zucker rats

Am. J. Physiol.

Insulin binds to specific receptors and stimulates 2-deoxy-d-glucose uptake in cultured glial cells from rat brain

J. biol. Chem.

Insulin stimulates macromolecular synthesis in cultured glial cells from rat brain

Am. J. Physiol.

Insulin is released from rat brain neuronal cells in culture

J. Neurochem.

Evidence for CNS insulin synthesis

Transcription of the insulin gene in the brain and submandibular gland of the rat

Pediatr. Res.

Ontogenesis of the insulin receptor in the rabbit brain

Hormone Res.

Insulin immunohistochemistry of rodent CNS: apparent species differences but good correlation with radioimmunological data

Histochemistry

Insulin and C-peptide in human brain neurons

J. Hirforsch.

Commentary
The cellular and physiological actions of insulin in the central nervous system