Pancreas - Diabetes Mellitus (Type I & Type II)

The gland organ Pancreas is a part of the Endocrine & Digestive system.  It lies deep inside the abdomen. It is sandwiched between stomach & spine. It lies partially behind the stomach. The rest of the pancreas is nestled in the duodenum(small intestine). The pancreas comprises endocrine and exocrine cells. The regions of the pancreas that contain endocrine cells are called the islets of Langerhans as it was first discovered by a German Anatomist Paul Langerhans. Endocrine cells are the harmone producing cells and the exocrine cells produce digestive enzymes that are necessary for the food to be digested. The islets constitute roughly 2% of the pancreas and there are different islets cell. But the most important of all are the alpha cells and beta cells of the islets of Langerhans. The alpha cells produce glucagon and the beta cells produce insulin. Alpha cells make up 15-20% and beta cells 65-80% of the total islet cells.

Insulin is a 51 amino acid protein chain. Its regulatory role in blood sugar levels was discovered in 1921. Until 70s, before the Recombinant DNA Technology was discovered, Diabetes Mellitus both T1(Type I) diabetes was considered lethal and T2(Type II) diabetes also leading to severe complications. The only alternative was to restrict the person's diet to low calories or injecting pig or cow insulin. The pig insulin differs by 1 amino acid and cow insulin by 3 amino acids from the human insulin. But some people developed allergies to this 'foreign' insulin.

DNA Recombinant methods were developed in 1972 by Stanley Cohen of Stanford University & Herbert Boyer of University of California, San Francisco. Boyer had written in his high scool year book that he dreamt of becoming a successful businessman one day! Luck knocked on his door through a 26 year old venture capitalist Bob Swanson in 1976 and world's first biotech company 'Genentech' resulted out of that meeting. The hunt for human insulin using recombinant methods was in full swing by Genentech. So, were other researchers joined the race and this crazy race had federal regulations. Genentech was smart as they tried to synthesize the gene chemically and induce E. Coli bacteria to produce insulin. After final experimental confirmations, Genentech would go public in 1980. Immediately the shares rose from $35 to $89 and during that time, it was the rapid escalation in value in the history of Wall Street. Soon, Boyer & Swanson found themselves worth $66 million apiece. Biotech brought big bucks and also dirty politics !!!

The organs involved in diabetes are islet cells of the pancreas that produce insulin, liver, muscle, brain and fat. Insulin is a harmone and also a protein which is made up of amino acids. Insulin regulates the glucose levels in the body. Whatever food we eat is broken down into fat, protein and simple sugars from carbohydrates. Liver is the organ that processes all these nutrients into glucose, a type of simple sugar, which is the main source of energy/fuel for the 400 trillion cells in the human body. Glucose molecules float in the bloodstream waiting to be utilized by the cells. But glucose can enter the cells only in the presence of insulin which stands like a guard at the door. If there is no insulin, then glucose can not enter the cell and glucose deprived cells can lead to serious complications. Since glucose is the source of energy, untreated diabetics, with no or little insulin, feel tired and exhausted all the time. If glucose can't enter the cells, then its level builds up in the bloodstream leading to high blood sugar.  

Remember all the organs perform specific functions and they interact with one another harmoniously to keep the body in optimal health. When one organ is disrupted, it puts pressure on other organs! So, what happens when sugar levels shoot up in the bloodstream? Kidneys work harder to remove the excess sugar by producing urine and thereby excreting it. What is urine? Its mostly water with some elements(am skipping the elements part for the moment)! To produce urine, kidneys have to extract water from tissues. When this occurs, the tissues become dehydrated. So, untreated diabetics feel thirsty and drink lot of water, a condition known as polydipsia. Drinking excessive amount of water is going to lead to frequent urination which is known as polyuria. When cells lack glucose, they begin to burn fat and finally protein. This leads the diabetics to eat excessive eating, to replenish the lost protein, called polyphagia. Do you realize now that body has started going in vicious cycle?

When there is no glucose, the cells look elsewhere for alternative fuel. Liver produces acidic substances called ketones. If too many are produced and not used, then these build up in the blood and lower the pH of blood making it acidic. Blood is alkaline (pH>7 means alkaline; pH<7 means acidic and pH=7 means neutral) and maintains a pH in a narrow range 7.38-7.48. When blood becomes acidic, a condition known as ketoacidosis, it can be life threatening resulting in coma. Some of the symptoms of ketoacidosis are vomiting, rapid breathing, abdominal pain, tiredness & drowsiness.  If diabetes persists, then the walls of the blood vessels may get damaged by cutting the blood supply to the kidneys, eyes and limbs and in some cases leading to amputation of the limbs.

T1, also knowns as Juvenile Diabetes, is autoimmune related. In rare cases, T1 affects elderly people also. Body's own immune system sees insulin producing cells of the Pancreas as foreign/invader and starts attacking them. I had mentioned in one of my other article that there are two types lymphocytes of immune cells(leukocytes) namely T(Thymus) lymphocytes and B(Bone Marrow or shortly BM) lymphocytes. In most of the immune related diseases, it is the rogue cells T that does havoc to the body. Both T & B cells are produced in the bone marrow only but T cells leave the bone marrow and mature in Thymus while B remains in bone marrow. We will see in detail how the two play in many disorders/diseases and also our own well being. In Type 1, the T cells completely disable the insulin producing beta cells of the pancreas and hence patients have to be on insulin injections for life. Or, need to go for pancreas transplant. First of all, the organ is scarce and secondly pancreas transplant is 'far' from being even remotely 'successful' in transplants. In T1, half a dozen genes have been identified so far that play a role for inducing this. Immune system is the only organ other than brain, that has 'memory'. The day we solve the mystery of the 'thinking' of the brain, we will find cures for the immune related diseases. For T1, the best drug is 'insulin' which is available in the form of shot on prescription. In some T2 cases too, the patients may need to take shots.  

Currently Type II(T2) Diabetes affects 15 million people in the United States and 150 million worldwide. If T2 is not treated, can result in serious complications including heart attack, stroke, kidney failure, blindness, and peripheral arterial disease which require amputations. In T2, very little insulin is produced or it is produced but not utilized properly. T2 is known as 'silent killer'. T2 is mainly caused by obesity which is 80% genetically inherited. T2 is a polygenic disorder, meaning many genes are involved. Some 20 genes have been indentified in T2's case.  But it can be controlled with diet, exercise and environment. There are seven class of oral medications for T2, available only on prescription:

1. Amaryl (glimepiride)
2. DiaBeta (glyburide)
3. Diabinese (chlorpropamide)
4. Glucotrol (glipizide)
5. Glucotrol XL (glipizide long-acting)
6. Glynase (glyburide)
7. Micronase (glyburide)
8. Tolazamide
9. Tolbutamide

The first seven drugs have sulfonylureas which stimulate the pancreas to produce insulin which in turn lowers the blood glucose levels. The last two drugs are combination of drugs from the class of seven drugs.

There is a third type known as Gestational Diabetes Mellitus (GDM) which occurs in some women during pregnancy. For most women, who never had diabetes before, the blood sugar levels become normal after the baby is born. Women with GDM deliver healthy babies by following a healthy diet, regular physical activity and maintaining a healthy weight. But these women have a higher risk of developing T2 in later years. In rare cases, women with GDM and without preventive care, can develop complications and deliver babies who are put at risk for hypoglycemia(low blood sugar), jaundice, respiratory disstress syndrome(difficult to breath), and macrosomia(baby's body being larger than normal).

Many people are not even aware of Pancreas in the human body until symtoms occur !