1. DIABETUS

2. Andrew Vidalis Dan Ramnytz Mods 0-2

3. Glucose

4.  After ingesting food, your meal is broken down and digested.  As a result, glucose is released into your bloodstream.  High concentrations of glucose in the blood are a signal for the beta cells of the pancreas to release insulin. (>90mg/100mL)  This hormone works like a key to unlock the protective cell membranes and allow the passage of glucose into the cell to be used for energy.

5.  Insulin works to decrease the concentration of glucose in the blood and facilitate transport into the cells by binding to special receptors embedded in their membranes.  There are some tissues such as the brain and the liver that do not require insulin for glucose uptake, however most of our cells would not be able to access blood glucose without it.  Glucose is the energy source for all cells and is required for their, and ultimately our, survival. Mechanisms of Insulin Secretion

6.  The insulin signaling pathway includes an insulin receptor that is made up of two receptor subunits (α and β) that are located on the outside of the cell membrane and two subunits that penetrate through the membrane.  These subunits are chemically bonded together. The extracellular (outside the cell) subunits contain a binding site for insulin.  When insulin binds to the extracellular subunits, it activates a chemical reaction that travels through the linked subunits into the cell.  This mechanism sends chemical signals to proteins within the cell and causes them to alter their activity, which in turn initiates the movement of glucose transporters to the cell membrane.

7.  Glucose transporters are the cells' method for transferring glucose through the cell membrane from the blood and into the cell.  The glucose transporters are inside vesicles within the cells' cytoplasm. However, they are useless to transport glucose without activation from insulin.  The binding of insulin to the cell leads to movement of the vesicles to the cell membrane, where they fuse with it and insert the glucose transporters. This gives the cell the ability to take in glucose from the blood.  When blood glucose levels decline, insulin stops binding to the cell receptors and the glucose transporters are moved back into the cell's cytoplasm.

9.  As glucose concentration in the bloodstream rises, beta cells in the Islets of Langerhans in the pancreas begin to form more ATP because of cellular respiration. ATP sensitive gateways for K+ ions close when enough ATP is present. This leads to the expansion of the cell membrane which activates voltage-gated Ca 2+ channels. This leads to the release of insulin from the cell via vesicles.

10.  Glucose gets converted to Glucose-6-Phosphate (G6P) through Glucokinase, and G6P is then oxidized to form ATP. This process inhibits the ATP sensitive potassium ion channels of the cell causing the potassium ion channel to close. The closure of the potassium ion channels causes depolarization of the cell membrane, which in turn causes the cell membrane to stretch and allow voltage-gated calcium channel on the membrane to open. This influx of calcium ions then stimulates fusion of the insulin vesicles to the cell membrane and secretion of insulin in the extracellular fluid outside the beta cell, thus entering the bloodstream.

12.  Type 1 diabetes is caused by an autoimmune attack on the pancreas. Specifically beta cells in the Islets of Langherhan.  This attack may be caused by many different factors. For whatever reason, the autoimmune cells target and attack the pancreatic cells as if they are foreign. This attack may be triggered by a recent immune response to an unrelated infection, or may be entirely random.  People may be susceptible to type 1 diabetes because of genetics or unhealthy habits.

13.  This attack on the pancreas results in a lack of, or total loss of, insulin in the bloodstream.  Left untreated, cells will not have fuel for cellular respiration, and blood-glucose levels will rise.  As the pancreatic cells die, the patient will lose energy and begin to urinate frequently. This urination is due to the body dumping glucose into the urine in order to alleviate the blood-glucose levels.  Over time, if treated poorly, frequently high blood- sugar levels will lead to the destruction of small blood vessels and capillaries throughout the body. This may lead to loss of toes, fingers and vision over time, along with many other effects such as inhibited kidney function, etc.

14.  For type 1 diabetics, the only treatment is frequent insulin injections via syringe/insulin pen or insulin pump in order to replace the lost insulin in the blood.  Diabetics must monitor their blood sugar levels and respond appropriately with injections as the pancreas usually would.  It is important for diabetics to also avoid low blood sugar as well as high, since low blood-sugar may result in seizures, tunnel vision, and death.  Exercise may lower blood sugar levels in diabetics, however it only results in muscle cells using glucose.  It is also important for people to respect diabetics since they lead difficult lives and you should give them free money and good grades.

15.  Pancreas transplants exist, however this means the patient must take immuno-suppressive drugs to suppress rejection of the new organ. If it is rejected, the patient must undergo further transplants.  In Europe artificial pancreases are in use. These may be in or outside the body and function as a real pancreas would.  However, these are not legal in America because corporations would make less money.  Another illegal thing in America is stem cell research which promises to cure diabetes in the future with full replacements of the pancreas. Along with a host of many other potential cures, this is the most promising cure as of now. Still, no money = no cure.

16.  Excessive body weight, lack of exercise, and even genetics can increase one’s risk to develop type 2 diabetes  Insulin is produced but target cells don’t respond normally to insulin, there is insulin resistance  Glucose is not taken into target cells by the glucose transporters and blood glucose levels stay high  Treatment: insulin pills, insulin injections, diet, exercise, commitment to monitoring blood sugar levels

17.  The β-cells in the pancreas attempt to compensate for this insensitivity to insulin in the cells by the hypersecretion of insulin.  The hypersecretion is caused by an expansion of β-cell mass and alterations in the expression of key enzymes of β-cell glucose metabolism. Yet, it is unknown what allows the β-cell to allow for such compensations.

18.  The cause is unknown but is related to bodyweight and exercise  May be due to a defect in the glucose transporter  Causes of reduced glucose transport: ◦ impaired insulin signal transduction ◦ alterations in the traffic and translocation of GLUT-4  Signal transduction can develop problems from defects at IRS-1, IRS-2, and/or PI 3-kinase  Insulin receptor site (IRS) Phosphatidylinositol 3- kinase (PI 3-kinase)

19.  In addition to tyrosine phosphorylation, the insulin receptor may undergo serine and threonine phosphorylation, for example by cAMP-dependent protein kinase  Serine phosphorylation has been suggested to play a role in the decreased receptor tyrosine kinase activity observed in type 2 diabetes  Decreased tyrosine receptor kinase activity causes the glucose transporters activity to be impaired

21.  Treatment: insulin pills, insulin injections, diet, exercise, commitment to monitoring blood sugar levels  Type 2 diabetes may be cured by exercise and loss of weight  It is fairly unknown how sensitivity is restored this way, however it is known that being overweight increases a person’s chances of becoming insensitive to insulin.  By exercising and losing weight, one may reduce or cure type 2 diabetes.

22.  Further research on the causes and cures of Type 2 Diabetes  Scientists at Duke University developed a peptide drug that has heat-sensitive polymers attached to it  Turns into a jelly - allows for the drug to be broken down over time by enzymes  Benefits: fewer injections, less pain, cheaper

23.  http://circ.ahajournals.org/content/120/2/1 50.full http://circ.ahajournals.org/content/120/2/1 50.full  http://diabetes.diabetesjournals.org/content /49/2/284.full.pdf http://diabetes.diabetesjournals.org/content /49/2/284.full.pdf  http://www.livestrong.com/article/27924- insulin-signal-cell-glucose-blood/ http://www.livestrong.com/article/27924- insulin-signal-cell-glucose-blood/  http://science.howstuffworks.com/life/huma n-biology/diabetes2.htm http://science.howstuffworks.com/life/huma n-biology/diabetes2.htm  http://trololololololololololo.com/ http://trololololololololololo.com/  http://www.wired.co.uk/news/archive/2013- 01/29/diabetes-jelly-injections http://www.wired.co.uk/news/archive/2013- 01/29/diabetes-jelly-injections