Insulin and Glucose Administration Stimulates Fos Expression in Neurones of the Paraventricular Nucleus That Project to Autonomic Preganglionic Structures

Abstract

Insulin and glucose play a key role in the control of body energy homeostasis. However, the anatomical organization of the network of central insulin and glucose sensitive areas is still unclear. In the present study, we used a multiple-labelling technique combining retrograde tracing and Fos-like immunohistochemistry, to analyse the anatomical projections from hypothalamic neurones activated by the combined stimulus of insulin and glucose. After intraperitoneal injections of a bolus of insulin plus glucose, Fos-like immunoreactive neurones were observed in the paraventricular nucleus (PVN), ventromedial and arcuate nuclei, as well as the lateral hypothalamic area. In addition, neurones projecting to the autonomic preganglionic levels in the brainstem and spinal cord potentially involved in the control of glucose metabolism were identified by injections of fluorochrome tracers. Thus, Fluorogold was injected into the intermediolateral cell column of the lower spinal cord and Fast Blue was injected into the dorsal motor nucleus of the vagus. Perikarya of descending neurones were detected chiefly in the dorsal, medial and lateral parvocellular subnuclei and also in the posterior magnocellular subnucleus of the PVN. In contrast, insulin-glucose activated neurones in the PVN were observed mainly in the medial parvocellular and posterior magnocellular subnuclei. Fluorogold/Fos double-labelled neurones were only observed in the ventral zone of the medial parvocellular subnucleus. These data indicate that, within the PVN, there could be neurones responding to insulin-glucose administration, which are involved in the sympathetic control of the classical regulatory structures of body energy homeostasis, such as the liver and pancreas, and which could play a role in the output of the neuronal circuitry controlling food intake.

Neurons in the Rat Lateral Hypothalamic Area Integrate Information from the Gastric Vagal Nerves and the Cerebellar Interpositus Nucleus

“…Feeding behavior is closely linked to fl uctuation in the blood glucose level [9][10][11]27] , and it is well documented that about 40% of the neurons in the LHA are glycemiasensitive neurons [11,33] which may be involved in meal onset triggered by a blood glucose drop [28] . In this study, the correlation between the gastric vagal afferent inputs and the glycemia-sensitive neurons in the LHA was further documented.…”

“…One of the purposes of this study is to explore this issue and to examine whether the inputs from these two sources interact with each other. Since feeding behavior is closely related to fl uctuation in the blood glucose level [9,11,27,28] , the sensitivity of the recorded neurons to intravenous injection of glucose was also investigated. Our results demonstrate a convergence of gastric vagal and cerebellar IN afferent inputs to single LHA neurons, including cells sensitive to glycemia.…”

Chronic stress plasticity in the hypothalamic paraventricular nucleus

“…Several combined tract-tracing and Fos mapping studies indicate that brainstem-and spinal cord-projecting PVN cell groups are activated by water deprivation, insulin, lipopolysaccharide and acute restraint Carrasco et al, 2001;Stocker et al, 2004;Radley et al, 2006), suggesting that like the parvocellular CRH system, the preautonomic PVN is responsive to a wide range of stressors. The response of the preautonomic system to interleukin 1-beta is prolonged relative to that of the PVNmpd (Ericsson et al, 1994), suggesting that this system may respond to some stimuli with an extended time course.…”

Hyperglycemia does not increase basal hypothalamo-pituitary-adrenal activity in diabetes but it does impair the HPA response to insulin-induced hypoglycemia

“…As the sensing of falling blood glucose levels is crucial for glucose counterregulation, disruption of key glucose sensing mechanisms in hypothalamic neurons may be responsible for the attenuated response. The PVN contains neurons that are responsive to insulin and glucose administration (6). Increases in the number of Fos-like immunoreactive neurons in the PVN of rats with glucose infused into the brain have been reported (18,31).…”