The term homeostasis can be defined merely as a “steady state.” In the human body, homeostasis has a much more defined meaning; homeostasis in the human body is defined as the ability of the body to regulate internal functions to maintain a healthy balance. Homeostasis is essential because cells need a steady state to survive and to perform their various tasks systematically. It entails a stimulus, a receptor, the communication system and the effector. The stimulus refers to what is eliciting a change to the standard stability of the body, for instance, plasma glucose levels that change rapidly from time to time. A receptor, on the other hand, is what transmits signals to the communication system, which many times are the nervous system that is the brain. It receives the signals and sends commands to the effector, which is an organ, required for reinstating the stability. Failure of the nervous system results in various disorders, for instance, metabolic diseases such as diabetes, which is the imbalance in the homeostatic glucose levels in the body that comes about where there is insulin resistance, and decreased insulin production (Lam et al. 2009). This paper aims to discuss the homeostasis of blood glucose regarding the central nervous system.
Both the endocrine system as well as the nervous system maintain blood glucose levels because the entire body is dependent on glucose for energy provisions. The central nervous system is responsible for the regulation of not only glucose levels but also the energy needs of the body; hence, the brain maintains the blood carbohydrate levels within a narrow range because the entire body is dependent on plasma glucose for energy. According to Oomura et al. and Anand et al. the brain makes the regulation either directly or indirectly where feeding and satiety centre neurons present in the hypothalamus (that is those present in the lateral and ventromedial regions) firing rates changed with changes in the plasma glucose levels. The brain directly regulates glucose levels through the glucose-responsive and the glucose-sensitive neurons where the neurons directly alter the firing rates with changes in plasma levels although their effects are short-termed (Forbes &Cooper, 2013).
Glucose-responsive neurons speed up the firing rates when there are rises in the plasma glucose levels but cease when the glucose levels reduce. They act via the aid of ATP-sensitive potassium ion channels present in the beta cells in the pancreas. The ion channel becomes inactive when it directly binds to ATP and is activated when it is phosphorylated. The channel closes when it binds to ATP from the plasma glucose, this leads to an increase in the intracellular potassium levels followed by an influx of calcium ions. Flow in calcium ions results in depolarization, which occurs to the release of insulin.
Consequently, the ion channel is a functional unit made up of the pore-forming group for potassium ions, a binding site for sulfonylureas. The sulfonylureas are essential for the ion channel functioning where binding to ATP results to inactivation of the channel thus secretion of insulin occurs although it has a different response to potassium ion openers, which bring insulin secretion through hyperpolarisation. The pore-forming group corrects the levels of potassium ions and Secreted insulin is responsible for the reduction of plasma glucose. However, there are many unresolved issues in regards to the concept.
Sulfonylureas receptors are also present at the GABA and glutamate nerve terminals. When there are increased glucose concentrations at the terminals, there is increased neurotransmitters release. Moreover, dopamine and norepinephrine neurotransmitters are glucose responsive because they respond to impulse firing despite their endings not containing the potassium ion channels. In the substantia nigra, the firing of the nigral neurons is entirely dependent on the glucose levels. The substantia nigra contains; the active site and the binding site of potassium ion channels, the terminals of GABA as well as the axonal terminal of glutamate. Therefore, a rise in plasma glucose levels results to the release of the inhibitory neurotransmitter (GABA), which inhibits the binding of glucose to the potassium ion channel thus, stopping the firing of the nigral dopamine neurons. Therefore, at high glucose level concentrations, there are the inhibitory GABA effects whereas at lower frequencies there is the dopamine stimulated firing. In addition to that reduced sulfonylureas concentrations enhance GABA release by acting on the high-affinity sulfonylureas receptor whereas raised levels stimulate the release of dopamine by working on the low-affinity sulfonylureas receptors.
The glucose response neurons contain phenotypes of different transmitters and peptides which are also present in the arc of the hypothalamus which all express potassium ion channel although the arc of the hypothalamus even express the neuropeptide Y which regulate the neuronal and metabolic impulses from the brain and other parts of the body. The arc also has the representation of leptin and insulin receptors which control the channel. The arc extends into the paraventricular nucleus of the hypothalamus which connects the neuroendocrine and the autonomic efferent pathways. The central neuropeptide Y brings about some events; a shit from the lipid to carbohydrate oxidation decreased satiety which results to increased food intake, decreased brown adipose thermogenic capacity as well as induces the release of food-induced insulin. The arc also regulates energy needs of the body through intrinsic and extrinsic signals relayed to it. It also has hormones such as oxytocin, vasopressin among others that are responsible for other homeostatic regulations.
The glucose-sensitive neurons as earlier stated, they directly respond to raised glucose concentrations by reducing the firing rate. The neurons also respond to food-induced cues, as well as regulate the energy homeostasis. According to Oomura et al., the neurons act through the sodium-potassium ATPase pump. The neurons are present at the amygdala and the lateral hypothalamus and also receive signals from the peripheral glucose-sensing afferents.
The central nervous system has the glucagon-like peptide-2 receptors, which regulate the energy needs of the body as well as the plasma glucose concentrations. Glucagon-like peptides are of two types that are type one and type two. They present in the hippocampus, nucleus tractus as well as the hypothalamic nuclei. They are both secreted from the endocrine L cells of the gastrointestinal tract; it is controlled by the incretin effect. The two are released from the preproglucagonergic in the brain stem. Leptin also stimulates their secretion. Glucagon-like peptide-type two regulates the growth of the pancreatic endocrine cells, the excitability of the postsynaptic membranes of the hypothalamic neurons, activates the phosphoinositol pathway thus leading to insulin secretion, and hinders glucose production, decrease glucagon secretion thus regulating food intake as well as maintaining glucose levels. The glucagon-like peptide acts through the G protein-coupled protein to enhance intestinal blood flow, gastric motility, epithelial homeostasis, and immunity, although it has limited effects on glucose homeostasis. It acts a ligand on the proopiomelanocortin receptor for the regulation of energy needs in the body. Alpha-melanocyte stimulating hormone binds to melanocortin receptor to regulate overall body weight, energy balance as well as glucose balance. In addition to that, the glucagon-like peptide decreases cholinergic input, increase endothelial relaxing factor to the gut thus decrease gastric emptying. The brain directly regulates glucose levels by eliciting insulin and lectin direct action on the proopiomelanocortin cells. Peripherally, glucagon-like peptide brings about glucose homeostasis by promoting glucose absorption in the intestines as well as the secretion of glucagon from the alpha cells of the pancreas islet of Langerhans. The central nervous glucagon-like peptide regulates insulin sensitivity through the hepatic vagal input (Levin et al, 1999).
Insulin is the primary hormone responsible for the regulation of glucose levels. Central insulin that is located in the brain acts through the potassium ion channels to regulate the peripheral concentrations of glucose; this can be interfered by the administration of potassium channel blockers. The brain has a circuit with the liver in which the vagal impulses from the brain are relayed to the liver as the effector organ to restore the average glucose levels. The vagal input stimulates the interleukin transducer and activator of transcription cascade in the liver to reduce raised glucose concentrations. The phosphoinositol pathway directly activates the potassium ion channel through hyperpolarisation in the proopiomelanocortin neurons.
Leptin is one of the many amino acids that is responsible for the regulation of glucose concentrations in the body. It achieves this by acting on the pancreas to enhance hepatic and extra-hepatic actions of insulin on glucose. It is efficient in cases of resistance associated with a diet that is high in fats. There are leptin receptors present in the arc of the hypothalamus that upon ligand binding results in the regulation of the glucose levels via the two intracellular cascades; that is the STAT3 dependent pathway, which suppresses glucose levels in an overfed stomach (Guan, 2014).