Kidney's relation with glucose homeostasis
Discuss about the Diabetes for Thirst and Hungry Polydipsia.
Diabetes, often referred by healthcare professionals are diabetes mellitus mainly refers to the group of metabolic disorders in which the persons suffer from high blood glucose level. This may be either because insulin that helps in energy production by breaking glucose are either less or the body may not response to available insulin present or both (Nolan et al. 2015). They experience different types of symptoms like frequent urination, increasing thirst (polydipsia) and hungry (polyphagia). It affects the glucose homeostasis of the body. Different organs are involves in glucose homeostasis and are also affected by diabetes. They are discussed below.
Kidney is found to be intricately associated with the glucose homeostasis. Diabetes which is associated with the increase of the blood glucose level is mainly seen to create destruction to the blood vessels in the kidneys. When the vessels of the blood in the kidney get damaged, they fail to perform properly (Wilding 2014). Often patients who have diabetes are seen to have high blood pressure and this becomes responsible for the damaging of the kidneys. When the blood vessels in the kidneys get damaged, kidneys fail to clean the effectively. As a result of this, bodies are seen or retain more salt as well as water. This is indeed seen to result in the increase of the weight as well as swelling of the ankles of the individuals.
When individuals are in fasting condition in the healthy individuals, the kidney is one of the organs that take an active part in the contribution of about 20 to 25 % of the glucose. This glucose gets released in the circulation via the procedure of the gluconeogeneis where glucose is produced from non-carbohydrate carbon substances. This form of renal gluconeogenesis is found to occur in the proximal tubular cells in the renal cortex. Under normal situation, the insulin as well as the catecholamine like that of the adrenaline mainly regulate this. Insulin is mainly seen to reduce different types of procedures of the renal gluconeogenesis directly. It also helps in the reduction of the availability of the gluconeogenic substrates (Terami et al. 2014). These may include glycerol, lactate as well as glutamine. This results in reduction of the glucose into the circulation. During the postprandial stage, renal gluconeogensis is seen to increase in comparison to that of the post absorptive stage. This increase of renal glucose helps in repleting the hepatic glycogen stores mainly by permitting suppression of the hepatic glucose release. Posprandial increase of the lactate as well as the amino acids that are the precursors of the gluconeogeneis and also increase in the sympathetic nervous system activity are the main reasons. It results for about 60% of the release of the endogenous glucose during the postprandial period (Lennerz et al. 2015).
Renal gluconeogenesis and its regulation
In case of patients who are suffering from the diabetes, there is decrease in the production of insulin. Therefore, the renal as well as the hepatic glucose are released at an increased rate as a result of the increased gluconeogenesis. Increased gluconeogenesis mainly takes place as insulin is not produced at a sufficient rate too reduce or balance the production of the glucose from the sources (Nolan et al. 2015). Insufficient insulin also cannot reduce the availability of gluconeogenic substrates in the blood of the individuals. Researchers have put forward interesting information (Thorens 2015). They are of the opinion that renal glycogenolysis is very less or take place minimally in healthy individuals. However, they are seen to play an important part in the role of increasing renal glucose release in the patients with diabetes. This is mainly because of the accumulation of glycogen in diabetic kidneys.
Pancreas is an important glandular organ that has both exocrine as well as endocrine tissues participating in both the function. The exocrine portion is mainly seen to release the different bicarbonate as well as the digestive enzymes in the gastrointestinal tract. The endocrine portion is mainly seen to release hormones in the blood. The tiny endocrine glands that are correctly called as the islets of Langerhans contain different types of cell types (Chambers et al. 2017). These cell types are mainly seen to release different important hormones that help in glucose homeostasis. The alpha cells release somatostatin as well as gastrin and the beta cells are seen to release the insulin as well as amylin. The delta cells are seen to release somatostatin and gastrin. The PP cells are mainly seen to release pancreatic polypeptide.
Insulin that is released from beta cells of islets of Langerhans is mainly seen to be involved in up taking and glucose as well as other energy containing molecules. There are counter-regulatory hormones released from the pancreas that oppose the actions of insulin and thereby promote glucose release. These hormones that are antagonistic in action to that of the insulin are the glucagon from the beta cells of the islets, glucocorticoid cortisol from the adrenal cortex and the growth hormone of the pituitary gland (Rafacho et al. 2014). Again, on the other hand, glucagon like peptide 1 or the GLP1 from the gastrointestinal tract are mainly seen to enhance the release of the insulin in response to any ingested meals and again the amylin is mainly seen to cause suppression of the endogenous production of glucose in the liver. After a meal is taken, complex carbohydrates in the team are seen to break down the monosaccharide like the glucose, galactose and the fructose mainly in the lumen of the GI tract. They are then transported to the GI epithelial cells with the help of combination of active as well as passive apical membrane transporters. Sugars then pass via intercellular spaces with the help of the basal membrane transporters to that of the blood stream. When the glucose level in the blood is seen to result in the release of the insulin from the beta cells of the islets that then enters in the portal vein. Therefore, liver receives the highest number of insulin as it receives the huge number of glucose from digestive tract. Other energy storing organs like skeletal muscles, adipose tissues and others also take lots of glucose and therefore insulin makes them the primary targets (Roder et al. 2016). After acting on the glucose, they break down the glucose and produce energy in the cells. During the times of fasting as well as starvation, glucose concentration is mainly seen to decrease. In addition, at that particular time, the beta cells are seen to decrease the secretion of insulin and that the alpha cells are seen to increase the amount of glucagon that thereby helps in increasing the levels of glucose in the blood from the energy stores.
Pancreas and its role in glucose homeostasis
In type 1 diabetes, the beta cells that produce insulin are mainly seen to be attacked by the immune system of the body. This results in the destruction of the beta cells and therefore the pancreas is seen to try its best to produce insulin to keep the blood glucose levels low. However, when it fails to produce sufficient insulin for this reason, symptoms of diabetes are seen to occur (Cheng et al. 2016). In the type 2 diabetes, the body is seen to build up resistance to insulin and therefore more and more insulin is required for bringing the blood glucose level down. This creates pressure on the pancreas to produce more and more insulin than it normally does. Excessive pressure may result in the pancreas failing to produce insulin after a particular period and therefore the glucose level of the blood is seen to increase at a very high level. Therefore, this aspect results to the situation where the functioning of the pancreas fails and the patients suffer from diabetes.
Hypothalamus as well as the brain is seen to play an important role in the glucose homeostasis. The central nervous system is seen to mainly regulate fat metabolism as well as food intake, body weight as well as glucose homeostasis. Many of the researchers are of the opinion that molecular defects in type 2 diabetes are mainly seen to reside in the hypothalamus. The hypothalamus is mainly seen to comprise of two types of cells. These are the glucose excited GE and the glucose inhibited GI (Steinbech et al. 2015). GE is mainly seen to increase glucose concentration whereas GI is mainly seen to decrease glucose concentration. They are mainly seen to be located in the ventomedial (VMH), arcuate, lateral, paraventricualr as well as dorsomedial areas of the hypothalamus. Nucleus of the solitary tract, basolateral medulla as well as dorsomedial nucleus of vagus are also seen to be related with the glucose homeostasis.
Ventromedial hypothalamus is mainly seen to comprise of the sympathetic nucleus and thereby helps in up regulation of the plasma glucose. This helps in the decreasing of the hepatic glycogen. The lateral hypothalamus is mainly seen to be comprising of the parasympathetic nucleus and is thereby seen to be down regulating the plasma glucose. After nutrient is seen to be present, glucose is gradually absorbed and therefore sent in equal thirds to liver, skeleton muscles and thereby adipocytes (Steinbech et al. 205). Acetyal choline is mainy seen to be released from vagus as well as others like the VIP, gastrin release peptide, and pituitary adenyalte cyclate activated peptide – all take part in the linking of the central nervous system to that of the hepatic glucose production axis. Sympathetic nerves are mainly seen to be activated by the stress as well as hypoglycemia. They are seen to produce neurotransmitter, epinephrine as well as nor-epinephrine. These are mainly seen to act on the liver and thereby increase the glucose production and decreasing of the glucose uptake by the skeletal muscles (Ott et al. 2015). This is seen to play an important role in the hindbrain-induced suppression of the hepatic glucose production. In the normal situations, the neurons in the arcuate nucleus or the ARC of the hypothalamus have been found to be able to sense the nutrient levels mainly the glucose as the lipids. It also helps to sense the different hormonal signals such as insulin as well as leptin. This is mainly seen to be controlling the eating behaviors as well as hepatic glucose production. The main mechanism of this sensing is seen to involve ATP-sensitive potassium channels (KATP channels) (Tarussio et al. 2014). This type of channel is mainly expressed in both the neurons as well as the beta cells. It is mainly seen to comprise of a homo tetramer. This is in turn of two units - a potassium inward rectifier subunit KIR6.2 and sulfonylurea receptor 1 (SUR1), a member of ATP-binding cassette (ABC) super-family. Glucose is mainly seen to serve as the signal for the activation of the neuronal KATP channels. This results in the decreasing of the hepatic glucose production. The insulin is also seen to activate KATP channels that is present in the hypothalamus. On the other hand, reduced production of glucose from the liver also takes place when raising the levels of long chain fatty acid-Coenzyme A (LCFA-CoA) or due to the inhibition of the hypothalamic fatty acid oxidation as they activate the KATP (Morgan et al. 2015). Therefore, when insulin is decreased in the blood, the above mentioned actions cannot take place and this results in the production of glucose in the blood stream.
Types of cells involved in glucose homeostasis
It is seen that when diabetic neuropathy takes place, there is damaging of the nerves. High blood sugar is mainly seen to injure the nerves throughout the body. Diabetic neuropathy is therefore seen to damage nerves mainly in the legs as well as in the feet. Defects in the central nervous system thereby affects the glucose level in the blood as it can no more control the production of glucose from the liver as well as the other organs. Hence, glucose levels increases in the blood and may in turn affect several other nerves resulting in neuropathy. These may make the patients suffer from pain as well as numbness in legs, feet as well as digestive systems, blood vessel, heart and many others.
From the entire discussion, it become clear that the glucose homeostasis is one the most important phenomena that is important for energy production and different physiological processes of the body. It is mainly seen that kidney, pancreas as well as nervous system are closely associated with this mechanism. Therefore, knowledge about this systems are to be known so that proper care can be taken when patients are affected by diabetes.
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