New genetic loci link adipose and insulin biology body fat distribution
2. Describe how insulin release from the pancreas is regulated by changes in blood glucose levels. Include details of all the cells/tissues involved.
3. Describe the cell signalling pathway (including details of the downstream effector) that is activated in response to insulin to promote glucose uptake via glucose transporters.
2. Insulin is a protein in nature. It is made of a dimer composed of two chains of amino acids which are held together by bonds of disulphide. It is made of 51 amino acids. It is made and released from beta cells of the pancreas. As echoed by Craft et al (2016), the levels of glucose in blood are kept within range by a loop mechanism (negative feedback) in an attempt to keep the body systems in balance. The feedback mechanism operates in a manner such that when the blood glucose levels are high, the body looks for ways of reducing these levels to normal. When levels of blood glucose rise, either from the digestion of a meal or from glycogen-glucose conversion, insulin hormone is released from a glandular group of cells within the pancreas called Langerhans where the b cells reside. The levels of glucose in blood are detected directly by beta cells of the pancreas. There are other causes of increase in blood sugar levels. These include the hormone adrenaline, steroids, infections and trauma (Shungin et al (2015)). GLUT 2 transporters form the transport channels where glucose enters the beta cells. This glucose is then phosphorylated by kinases and is converted to pyruvate in the cytoplasm. The breakdown of glucose involves a series of steps in a process called glycolysis into two molecules of pyruvate. The broken down glucose in form of pyruvate enters the mitochondria and is further broken down to water and carbon (IV) dioxide whereby ATP is formed by addition of phosphate molecules. The ATP from the mitochondria migrates into the cytoplasm, where it inhibits ATP sensitive potassium channels, reducing potassium efflux. This causes increased positive charge as potassium molecules are cations. This causes depolarization of the beta cell and calcium enters the cell via voltage gated calcium channels (Fajans et al (2016)). The calcium entry causes the release of secretory granules containing insulin hence triggering the release of insulin from b cells. The liver has several functions in the body and is involved in glucose metabolism. There are several processes that occur in the liver as pertains glucose and these include the formation of glucose, (gluconeogenesis), the breakdown of glycogen, (glycogenolysis) and glycogen synthesis. Insulin being a hormone involved with glucose regulation therefore affects the liver. It causes the liver to convert excess glucose into glycogen and most of the body cells mainly the muscle cells and those found in fat tissue to uptake the glucose via GLUT 4 channels leading to low levels of glucose in blood. Insulin is also involved in protein synthesis where it encourages conversion of circulating amino acids into protein. Examples of such amino acids are leucine and arginine. A high level of these compounds thereby stimulates secretion of insulin as they act in a similar manner to glucose by generation of ATP once they are metabolized. This leads to closure of potassium sensitive pumps in the beta cells causing insulin release. (Humphrey et al (2015). Hypoglycemia (low blood sugar levels) on the other hand reduces insulin release. According to Sandler et al (2017), low blood glucose levels at the same time triggers the release of four hormones which counter the activities of insulin of which the principle hormone that counteracts this effect is glucagon. These hormones work hand in hand to ensure that glucose levels in blood are increased to normal hence homeostasis is achieved
3. The receptor pf insulin is a complex made of alpha and beta subunits. It is activated by either insulin or insulin like growth factors. As stated by Canfora et al (2015), binding of insulin or insulin like growth factors to the alpha subunit leads to a change in arrangements resulting into down cascade where tyrosine molecules within the beta subunit are phosphorylated. The resulting pathway causes a series of downward cascade involving a number of enzymes and amplification sequences that lead to glucose storage. Insulin stimulates glucose uptake by cells including myocytes and cells found in fat tissues (Anhê et al (2015)). It does so by inducing changes that lead to the migration of a transporter of glucose called GLUT 4 from the intracellular storage to the plasma membrane. Enzymes involved in the process including P 13 and kinase and AKT are known to play an essential role in GLUT 4 movement. According to Jung et al (2014), the activation of the receptor complex leads to a series of downward activation of a gene encoded protein (Cbl) through phosphorylation attached to second messenger CAP. The complex formed between the two proteins then translocate to lipid layers in the cell membrane. The former (Cbl) after this binds crk associated with an exchange factor C3G. The exchange factor then activates components of a larger family specifically tc10 that enhances movement of GLUT 4 to the cell membrane by activating an anonymous adaptor molecule.