Parallels to brain control of thermoregulation
المؤلف:
Holt, Richard IG, and Allan Flyvbjerg
المصدر:
Textbook of diabetes (2024)
الجزء والصفحة:
6th ed , page 134-135
2025-10-27
50
Brain control of thermoregulation offers a useful paradigm for understanding control of glucose homeostasis by the CNS. To ensure the stability of core body temperature, changes in ambient temperature are continuously relayed from afferent thermosensory fibres supplying the skin. These neurons project to the spinal cord, where they synapse onto ascending sensory neurons that ultimately supply neurons in the hypothalamic preoptic area (Figure 1). Preoptic area neurons in turn transduce this thermosensory input into adaptive responses that govern both heat production and dissipation (e.g. activation of brown adipose tissue, shivering, cutaneous vasoconstriction) so as to preserve the constancy of the brain’s temperature.
Fig1. Comparison of central thermoregulatory and glucoregulatory systems. The thermoregulatory system senses changes in external temperature via afferent thermosensory fibres supplying the skin, and conveys this information via a multisynaptic pathway to the hypothalamic preoptic area (POA). In this brain area, relevant afferent input is transduced into adaptive changes in heat production and dissipation that effectively maintain internal body temperature within a narrow range. Brain control of whole- body glucose homeostasis is hypothesized to employ an analogous system whereby afferent input regarding the circulating glucose level is conveyed to glucoregulatory neurocircuits in the hypothalamus and elsewhere by glucose- sensing neurons situated both in circumventricular areas of the brain that lack a fully formed blood–brain barrier and in peripheral vasculature (e.g. hepatic portal vein). In partnership with pancreatic islets, centrally driven changes in peripheral glucose production and utilization promote stability of the circulating glucose level. ARC, arcuate nucleus; BBB, blood–brain barrier; CNS, central nervous system; GE, glucose excited; GI, glucose inhibited; PVN, paraventricular nucleus; VMN, ventromedial nucleus. Source: Figure generated using http://Biorender.com.
Homeostasis of body temperature is therefore achieved via a multiorgan process that enables the brain to anticipate the need for adaptive responses before internal body temperature even begins to change. This degree of control would not be possible if the system relied on direct temperature sensing by neurons in the brain (rather than cutaneous sensory innervation), since the brain’s temperature would have to change before a homeostatic response would be engaged. Yet many key neurons in the medial preoptic area of the mediobasal hypothalamus that coordinate these responses have intrinsic temperature- sensing properties, analogous to the glucose- sensing properties of neurons involved in brain regulation of glucose homeostasis (Figure 1).
Taking this analogy a step further, both ‘warm- sensitive’ and ‘cold- sensitive’ neurons have been identified in the hypothalamic preoptic area, just as both ‘glucose- excited’ and ‘glucose- inhibited’ neurons populate hypothalamic nuclei involved in glucose homeostasis. Similarly, direct activation of temperature- sensing neurons can powerfully impact thermoregulation, and direct activation of glucose- sensing neurons can powerfully impact glucose homeostasis. Yet under physiological conditions, thermoregulation does not involve changes in brain temperature; instead, this intrinsic temperature- sensing capacity may provide a ‘back- up’ or ‘fail- safe’ mechanism that becomes important only when brain temperature deviates from its physiological range (owing to extreme environ mental exposure or failure of ‘first- line’ physiological defences). By analogy, direct sensing of glucose by neurons in the brain may be relevant primarily under pathological conditions, with input relevant to physiological control being provided primarily by afferent glucose- sensing neurons innervating the vasculature itself. From this perspective, the capacity to maintain brain glucose levels within a narrow physiological range, even in the face of wildly fluctuating variation in plasma glucose levels, seems likely to involve afferent input regarding the blood glucose level provided to the brain from the periphery (Figure 1).
In support of this type of mechanism, glucose- sensing neurons supply the hepatic portal vein and sense ingested glucose as it enters the circulation from the gastrointestinal tract, prior to entry into systemic circulation. An increase of glucose levels in the hepatic portal vein relative to the systemic circulation constitutes a portal signal that is detected by these neurons and implicated as a trigger driving the marked increase of hepatic glucose uptake elicited by a meal. Although the underlying mechanisms have yet to be fully elucidated, this response appears to be mediated via reduced SNS outflow to the liver, which in turn activates liver glucokinase, the rate- limiting enzyme for glucose uptake into hepatocytes. Defects in this response are seen in a canine model of diet- induced obesity, and support the hypothesis that reduced hepatic glucose uptake secondary to increased SNS outflow to the liver con tributes to glucose intolerance in this setting.
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