TY - CHAP
T1 - Origins of brain insulin and its function
AU - Nakabeppu, Yusaku
N1 - Funding Information:
Fig. 1.2 Origins of brain insulin and its function. Brain insulin is derived from pancreas, neurons and astrocytes (See text). Recently, it has been revealed that astrocytes play an essential role in long-term memory formation by converting glycogen into lactate and transporting it to the neurons (Newman et al. 2011; Suzuki et al. 2011). Astrocytes express GLUT1, thus take up glucose through BBB, and convert the intracellular glucose to glucose-6-phosphate and then store as glycogen (Jurcovicova 2014). Upon greater energy demand during synaptic transmission, glycogenolysis is triggered to produce lactate. Lactate is then transported to the extracellular space by monocarboxylate transporters (MCT1, MCT4), and is taken up by neurons via MCT2, and contributes to memory consolidation processes (Belanger et al. 2011; Bezzi and Volterra 2011; Stobart and Anderson 2013). While these steps are likely to be insulin independent, it has been reported that astrocytes express INSR and respond to insulin or IGF-1 (Garwood et al. 2015). Since insulin and/or IGF-1 promotes glucose uptake, glycogen storage and cell proliferation in astrocytes (Fernandez et al. 2017; Heni et al. 2011; Muhic et al. 2015), these events in the astrocytes have a contributory effect of an insulin-dependent increase in glucose utilization during increases in neural activity associated with hippocampal-dependent learning, as well as GLUT4-dependent glucose uptake by neurons. Insulin secreted by the neurons or astrocytes, thus plays essential roles to sustain high-energy demands associated with brain functions, while peripheral insulin contributes to maintenance of steady state level of brain function Acknowledgments This work was partly supported by a grant from the Japan Society for the Promotion of Science (KAKENHI: 17H01391). I thank all members in my lab and collaborators for their various comments and kind assistance.
PY - 2019/5/7
Y1 - 2019/5/7
N2 - The brain or central nervous system (CNS) utilizes a vast amount of energy to sustain its basic functions, and most of the energy in the brain is derived from glucose. Whole-body energy and glucose homeostasis in the periphery of the human body are regulated by insulin, while the brain had been considered as an “insulin-insensitive” organ, because bulk brain glucose uptake is not affected by insulin in either rodents and humans. However, recently it has become clear that the actions of insulin are more widespread in the CNS and are a critical part of normal development, food intake, and energy balance, as well as plasticity throughout adulthood. Moreover, there are substantial evidence demonstrating that brain insulin is derived from pancreas, neurons, and astrocytes. In this chapter, I reviewed recent progress in roles of insulin in the brain, expression of insulin genes, and multiple origins of the brain insulin.
AB - The brain or central nervous system (CNS) utilizes a vast amount of energy to sustain its basic functions, and most of the energy in the brain is derived from glucose. Whole-body energy and glucose homeostasis in the periphery of the human body are regulated by insulin, while the brain had been considered as an “insulin-insensitive” organ, because bulk brain glucose uptake is not affected by insulin in either rodents and humans. However, recently it has become clear that the actions of insulin are more widespread in the CNS and are a critical part of normal development, food intake, and energy balance, as well as plasticity throughout adulthood. Moreover, there are substantial evidence demonstrating that brain insulin is derived from pancreas, neurons, and astrocytes. In this chapter, I reviewed recent progress in roles of insulin in the brain, expression of insulin genes, and multiple origins of the brain insulin.
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U2 - 10.1007/978-981-13-3540-2_1
DO - 10.1007/978-981-13-3540-2_1
M3 - Chapter
C2 - 31062322
AN - SCOPUS:85065661647
T3 - Advances in Experimental Medicine and Biology
SP - 1
EP - 11
BT - Advances in Experimental Medicine and Biology
PB - Springer
ER -