Unit 1 Lesson 6 Activity 3- Insulin and the Human Body Insulin Lecture Unit 1 Lesson 6 Activity 3- Insulin and the Human Body

Beta Cells in the Pancreas Insulin is synthesized in beta cells Insulin helps to regulate metabolism of carbohydrates and fats Insulin is secreted by the pancreas Without insulin to facilitate absorption of glucose the levels become too high Insulin is synthesized in the beta cells of the pancreas through a glucose transporter through facilitated diffusion. Insulin helps to regulate the metabolism of carbohydrates and fats absorbed in the intestines. Insulin is secreted by the pancreas when blood sugar increases. Without the absorption and use of glucose by the muscles in the body, the glucose levels would become excessive and toxic.

Figure 5 Diagram of the Insulin and Glucose Regulation Model An increase of glucose depolarizes the membrane surrounding the beta cells. Calcium from outside of the beta cell rushes into the beta cell. This increase of calcium facilitates the release of stored insulin. Once the glucose levels drop, insulin release slows down or stops. As carbohydrates are absorbed by the intestines, insulin is released from storage in the beta cells. This release is due to a depolarization of the cell membranes and calcium ions entering the beta cells. The granules within the beta cells secrete the stored insulin and it leaves the pancreas to enter the bloodstream. Cells in the human body contain receptors that are open to bind with the insulin hormone. This binding then encourages the cells to absorb the glucose in the body. Once the glucose levels fall to a nominal level glycogen synthesis slows down and ceases. bio.davidson.edu

Cells and Glucose Without insulin, cells cannot bind with glucose and use this energy source for needed survival. These cells would have to find alternative energy sources like fatty acids. Insulin acts like a doorway to the cells within the human body. Once the glucose levels decrease the pancreas secretes the enzyme glucagon that signals the liver to release glucose so levels in the body are maintained. In a meal that is high in carbohydrates, glucagon levels remain low so blood glucose levels do not increase to dangerous highs. With a meal high in proteins glucagon levels increase.

Figure 6 Insulin Receptor Insulin travels to the liver once insulin is released by the pancreas. This release of insulin affects carbohydrate and lipid metabolism (lipids are fatty acids that are not soluble in water). The insulin receptors are tyrosine kinase- membrane proteins. These proteins contain two alpha subunits and two beta subunits. The alpha units are outside of the cell (extracellular) and hold the binding site for the insulin. The beta subunits attach to the alpha units by sulfur bonds and extend through the plasma membrane into the cell cytoplasm. The two complexes are connected by a disulfide ( a sulfide containing 2 sulfurs) bond. http://arbl.cvmbs.colostate.edu

Insulin Receptor The insulin receptor has two alpha subunits in yellow and two beta subunits as shown in blue. The red lines are the sulfur bonds and form a disulfide bond between the two complexes. When insulin binds to the alpha subunit, the beta subunit phosphorylates. One of these substrates is IRS-1 and is the most studied. This serves as a docking center for activation of other enzymes to mediate insulin’s effects by a signal by a signal transduction process-to convert into another form. This then creates another biological response.

Carbohydrates and Lipids-Metabolism Glucose is regulated by insulin Glucose is extracted during digestion With an increase in glucose the pancreas secretes insulin The liver maintains constant levels of glucose within the boy Glucose is extracted during digestion and goes into the bloodstream. Insulin is secreted by the beta cells in the pancreas. Once insulin binds to the appropriate insulin receptors, cytoplasmic vesicles under the plasma membrane fuse with the plasma membrane and glucose transporters (Na+-independent and Na+-dependent) and break through the membrane. Yet until insulin binds to the cells, glucose cannot be utilized by muscle tissue or adipose (fat) tissue. Glucose also needs to be regulated and the phosphorylase A receptor measures the amount of glucose in the liver. With an influx of glucose, it binds to these receptors and alters the shape so it can dephosphorylate and release the insulin to stimulate the formation of glycogen. The glucose is changed into glycogen with the aid of insulin in the liver and blood sugar levels are maintained. When the liver builds up high levels of glycogen, glucose is then redirected into other metabolic pathways. This is how fatty acids are produced and leave the liver as lipoproteins.

Lipoproteins Used in other tissues like adipose Makes triglycerides Insulin inhibits the breakdown of fat in adipose tissue Insulin responsible for accumulation of triglycerides in adipose tissue The lipoproteins produced are often used in other tissues like adipose tissue to make triglycerides. Insulin inhibits the breakdown of fat in adipose tissue by inhibiting the intracellular lipase that hydrolyzes triglycerides to release the fatty acids. Insulin is responsible for stimulating further accumulation of triglycerides in fat cells of adipose tissue. Researchers from the Indian Institute of Chemical Biology have speculated that a new cell could be secreting insulin. Insulin was thought to be secreted only by beta cells in the pancreas, but it is now thought to also exist in adipocytes. The structure-function relationship seem to be similar and the amino acid sequences of Adpinsl and mammalian beta cell insulin can be related. As an insulin target cell, adipocytes can express the insulin gene and secrete the insulin protein to serve as a natural alternative to beta cell insulin.

Metabolic Reactions and Insulin Insulin stimulates Glucose transport Amino acid transport Glycogen synthase activity Increases rate of general protein synthesis Decreases lipolysis and protein degradation

Insulin and the Effect on the Human Body Insulin regulates many cellular processes Including: DNA synthesis, RNA synthesis, Cell growth, Protein and fat synthesis. Insulin is mainly concerned with the regulation of glucose uptake in the “clinical manifestation of diabetes.” High levels of glucose causes water within cells to move into the bloodstream by osmosis. Kidneys will then increase urine output to rid the body of the excess fluids. This is why diabtes is concerned with issues of an overproduction of “seet” urine. With a mutation of the insulin protein or insufficient amounts of insulin the body can develop diabetes.

Diabetes Diabetes can affect all ethnic groups. Idiopathic diabetes type I- is an insulin dependent condition that manifests usually in childhood. The beta cells are destroyed by an autoimmune response. Idiopathic diabetes Type II- Non-insulin dependent and is characterized by persistent hyperglycemia (excess glucose in the bloodstream). Many causes can be attributed, but obesity seems to be a common factor. Type II can often be controlled through a low carbohydrate diet. Secondary diabetes- has many causes including: Gestational diabetes that develops during pregnancy. Maturity onset diabetes that happens before age 25 causes include: Pancreatic disease, endocrine disease, drug-induced, mutations in genes or receptors Diabetes is often undetected. Many ethnic groups have a higher chance of developing Type II diabetes. These groups include African Americans, Hispanics, Native Americans, and Pacific Islanders. Diabetes if left untreated causes kidney failure and a host of other problems.

References www.arbl.cvmbs.colostate.edu www.bio.Davidson.edu