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Autonomic Regulation of Hepatic Glucose Production

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Abstract

Glucose produced by the liver is a major energy source for the brain. Considering its critical dependence on glucose, it seems only natural that the brain is capable of monitoring and controlling glucose homeostasis. In addition to neuroendocrine pathways, the brain uses the autonomic nervous system to communicate with peripheral organs. Within the brain, the hypothalamus is the key region to integrate signals on energy status, including signals from lipid, glucose, and hormone sensing cells, with afferent neural signals from the internal and external milieu. In turn, the hypothalamus regulates metabolism in peripheral organs, including the liver, not only via the anterior pituitary gland but also via multiple neuropeptidergic pathways in the hypothalamus that have been identified as regulators of hepatic glucose metabolism. These pathways comprise preautonomic neurons projecting to nuclei in the brain stem and spinal cord, which relay signals from the hypothalamus to the liver via the autonomic nervous system. The neuroendocrine and neuronal outputs of the hypothalamus are not separate entities. They appear to act as a single integrated regulatory system, far more subtle, and complex than when each is viewed in isolation. Consequently, hypothalamic regulation should be viewed as a summation of both neuroendocrine and neural influences. As a result, our endocrine‐based understanding of diseases such as diabetes and obesity should be expanded by integration of neural inputs into our concept of the pathophysiological process. © 2015 American Physiological Society. Compr Physiol 5:147‐165, 2015.

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Figure 1. Figure 1. Sagittal scheme of the sympathetic and parasympathetic control of the liver. Brain areas providing first‐order projections are indicated in red, brain areas containing second‐order neurons are indicated in blue, and those containing third‐order neurons are indicated in yellow. It is clear by comparing the parasympathetic pattern against the sympathetic pattern that far more second‐order cell groups are in control of the first‐order parasympathetic (i.e., DMV) than first‐order sympathetic (i.e., IML) motor neurons. RVLM also includes the catecholaminergic A5, C1, and C3 areas. Abbreviations: Ace, Amygdala, central part; ARC, Arcuate nucleus; Ba, Barrington nucleus; BNST, Bed nucleus of the stria terminalis; DMH, Dorsomedial nucleus of the hypothalamus; DMV, Dorsal motor nucleus of the vagus nerve; IML, Intermediolateral column of the spinal cord; INS; Insular cortex; LH, Lateral hypothalamus; MPO, Medial preoptic area; NTS, Nucleus of the tractus solitaries; OVLT, Organum vasculosum of the lamina terminalis; P, Pineal gland; PVN, Paraventricular nucleus of the hypothalamus; vPVN, Ventral part of the PVN; dPVN, Dorsal part of the PVN; RA, Raphe nucleus; RCA, Retrochiasmatic area; RVLM, Rostroventrolateral medulla; SCN, Suprachiasmatic nucleus; SFO, Subfornical organ; VMH, Ventromedial nucleus of the hypothalamus; X, Nervus vagus; ZI, Zona incerta


Figure 1. Sagittal scheme of the sympathetic and parasympathetic control of the liver. Brain areas providing first‐order projections are indicated in red, brain areas containing second‐order neurons are indicated in blue, and those containing third‐order neurons are indicated in yellow. It is clear by comparing the parasympathetic pattern against the sympathetic pattern that far more second‐order cell groups are in control of the first‐order parasympathetic (i.e., DMV) than first‐order sympathetic (i.e., IML) motor neurons. RVLM also includes the catecholaminergic A5, C1, and C3 areas. Abbreviations: Ace, Amygdala, central part; ARC, Arcuate nucleus; Ba, Barrington nucleus; BNST, Bed nucleus of the stria terminalis; DMH, Dorsomedial nucleus of the hypothalamus; DMV, Dorsal motor nucleus of the vagus nerve; IML, Intermediolateral column of the spinal cord; INS; Insular cortex; LH, Lateral hypothalamus; MPO, Medial preoptic area; NTS, Nucleus of the tractus solitaries; OVLT, Organum vasculosum of the lamina terminalis; P, Pineal gland; PVN, Paraventricular nucleus of the hypothalamus; vPVN, Ventral part of the PVN; dPVN, Dorsal part of the PVN; RA, Raphe nucleus; RCA, Retrochiasmatic area; RVLM, Rostroventrolateral medulla; SCN, Suprachiasmatic nucleus; SFO, Subfornical organ; VMH, Ventromedial nucleus of the hypothalamus; X, Nervus vagus; ZI, Zona incerta
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Peter H. Bisschop, Eric Fliers, Andries Kalsbeek. Autonomic Regulation of Hepatic Glucose Production. Compr Physiol 2014, 5: 147-165. doi: 10.1002/cphy.c140009