1 Introduction: The pancreas is a fish-shaped spongy grayish-pink organ about 6 inches long, narrow gland that is situated transversely

across the upper abdomen, behind the stomach and the spleen. The mid portion of the pancreas lies against the vertebral column, the abdominal aorta, and the inferior vena cava.The pancreas makes pancreatic juices and hormones, including insulin. The pancreatic juices are enzymes that help digest food in the small intestine. Insulin controls the amount of sugar in the blood. As pancreatic juices are made, they flow into the main pancreatic duct. This duct joins the common bile duct, which connects the pancreas to the liver and the gallbladder. The common bile duct, which carries bile helps digest fat, connects to the small intestine near the stomach. The pancreas is thus a compound gland. It is compound in the sense that it is composed of both an exocrine (ductal) and endocrine (ductless) gland. The exocrine tissue, called acinar tissue, produces important digestive enzyme precursors that are transmitted into the small intestine, while the endocrine tissue (contained in the islets of Langerhans) produces at least two hormones (insulin and glucagon) that are important in the regulation of carbohydrate metabolism. 2 What is the Pancreas? The pancreas is called the "hidden organ" because it is located deep in the abdomen behind the stomach. About six to eight inches long in the adult, the organ contains thin tubes that come together like the veins of a leaf. These tubes join to form a single opening into the intestine that is located just beyond the stomach. The pancreas produces juices and enzymes that flow through these tubes into the intestine, where they mix with food. The enzymes digest fat, protein, and carbohydrates so they can be absorbed by the intestine. Pancreatic juices, therefore, play an important role in maintaining good health. The pancreas also produces insulin, which is picked up by the blood flowing through the organ. Insulin is important in regulating the amount of sugar or glucose in the blood. 3. The location of pancreas: The pancreas is a gland about 6 inches long that is shaped like a thin pear lying on its side. It is located posterior to the abdomen and lies behind the

2 stomach and liver and in front of the spine. It has three areas: head (the wider end of the pancreas), body (the middle section), and tail (the narrow end). The pancreatic head adjoins the second part of the duodenum while the tail extends towards the spleen. The pancreatic duct runs the length of the pancreas and empties into the second part of the duodenum at the ampulla of Vater. The common bile duct commonly joins the pancreatic duct at or near this point. 4. Physiologic Anatomy of Pancreas: The pancreas is several hundred thousand clusters of cells called islets of Langerhans. The islets are endocrine tissue containing four types of cells. In order of abundance, they are the:

beta cells, which secrete insulin and amylin; alpha cells, which secrete glucagon; delta cells, which secrete somatostatin, and gamma cells, which secrete a polypeptide of unknown function.

Beta Cells a. Insulin Insulin is a small protein consisting of

an alpha chain of 21 amino acids linked by two disulfide (SS) bridges to a Beta chain of 30 amino acids.

Beta cells have channels in their plasma membrane that serve as glucose detectors. Beta cells secrete insulin in response to a rising level of circulating glucose ("blood sugar"). Insulin affects many organs. It

stimulates skeletal muscle fibers to o take up glucose and convert it into glycogen; o take up amino acids from the blood and convert them into protein. acts on liver cells o stimulating them to take up glucose from the blood and convert it into glycogen while o inhibiting production of the enzymes involved in breaking glycogen back down ("glycogenolysis") and o inhibiting "gluconeogenesis"; that is, the conversion of fats and proteins into glucose. acts on fat cells to stimulate the uptake of glucose and the synthesis of fat.

acts on cells in the hypothalamus to reduce appetite.

In each case, insulin triggers these effects by binding to the insulin receptor a transmembrane protein embedded in the plasma membrane of the responding cells. Taken together, all of these actions result in:

the storage of the soluble nutrients absorbed from the intestine into insoluble, energy-rich products (glycogen, protein, fat) a drop in the level of blood sugar b. Amylin

Amylin is a peptide of 37 amino acids, which is also secreted by the beta cells of the pancreas. Some of its actions:

inhibits the secretion of glucagon; slows the emptying of the stomach; Sends a satiety signal to the brain.

All of its actions tend to supplement those of insulin, reducing the level of glucose in the blood. Alpha Cells The alpha cells of the islets secrete glucagon, a polypeptide of 29 amino acids. Glucagon acts principally on the liver where it stimulates the conversion of

glycogen into glucose ("glycogenolysis") and fat and protein into intermediate metabolites that are ultimately converted into glucose ("gluconeogenesis")

In both cases, the glucose is deposited in the blood. Glucagon secretion is

stimulated by low levels of glucose in the blood; inhibited by high levels, and inhibited by amylin.

The physiological significance of this is that glucagon functions to maintain a steady level of blood sugar level between meals.

Delta Cells Delta cells secrete somatostatin. This consists of two polypeptides, one of 14 amino acids and one of The 28. Somatostatin has a variety of functions. Taken together, they work to reduce the rate at which food is absorbed from the contents of the intestine. Somatostatin is also secreted by the hypothalamus and by the intestine. Further information about somatostatin can be found by following the links. Gamma Cells The gamma cells of the islets secrete a 36-amino-acid pancreatic polypeptide, which reduces appetite. 5.The hormone is secreted by pancreas: The pancreas folds under the stomach, secretes the hormones insulin, glucagon, and somatostatin. About 70% of the pancreatic hormonesecreting cells are called beta cells and secrete insulin; another 22%, or so, are called alpha cells and secrete glucagon. The remaining gamma cells secrete somatostatin, also known as growth hormone inhibiting hormone (GHIH). The alpha, beta, and gamma cells comprise the islets of Langerhans which are scattered throughout the pancreas. The Islands of Langerhans secrete four hormones insulin, glucagon, somatostatin and pancreatic polypeptide. Insulin and glucagon have antagonistic effects on the blood glucose level. Insulin: (Latin insula, "island", as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormonethat regulates carbohydrate metabolism. Apart from being the primary effectors in carbohydrate homeostasis, it also takes part in the metabolism of fat (triglycerides) and proteins it has anabolic properties. It also affects other tissues.

Glucagon: It is a amino acid polypeptide hormone. Glucagon is a hormone with the opposite action to insulin. It is made in the pancreas and is involved in carbohydrate metabolism. It is released when blood glucose levels start to fall below a threshold level and triggers the liver to convert stored glycogen into glucose and release it into the bloodstream, raising blood glucose levels and so preventing hypoglycemia.

5 Somatostatin: It helps inhibit the release of insulin and glucagon. In addition, it also slows absorption of nutrients in the small intestine. Pancreatic polypeptide This pancreatic hormone prevents secretion of somatostatin by the pancreas. Also, pancreatic polypeptide inhibits contraction of the gallbladder wall and secretion of digestive enzymes by the pancreas.

6. The chemistry of pancreas hormons: The main pancreas hormons are insulin and glucagon. The chemistry of these hormons are as bellowa. The chemistry of insulin: Insulin has the empirical formula C254H377N65O75S6 Insulin structure varies slightly between species. Its carbohydrate metabolism regulatory function strength also varies. Pig insulin is particularly close to the human. The structure of insulin is below-

C254H377N65O75S6 b. The chemistry of Glucagon: Glucagon is a 29 amino acid polypeptide acting as an important hormone in carbohydrate metabolism. The polypeptide has a molecular weight of 3485 daltons and was discovered in 1923 by Kimball and Murlin.

6 Its primary structure is: NH2-His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-ArgArg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu-Met-Asn-Thr-COOH The structure of glucagon is below-

7. The synthesis of Pancreatic hormones: Glucagon and insulin are peptide hormones released from the pancreas into the blood, that normally act in complementary fashion to stabilize blood glucose concentration. The synthesis of insulin and glucagon hormon are discribed as belowSynthesis of insulin: Insulin is synthesized in significant quantities only in beta cells in the pancreas. The insulin mRNA is translated as a single chain precursor called preproinsulin, and removal of its signal peptide during insertion into the endoplasmic reticulum generates proinsulin. Proinsulin consists of three domains: an amino-terminal B chain, a carboxyterminal A chain and a connecting peptide in the middle known as the C peptide. Within the endoplasmic reticulum, proinsulin is exposed to several specific endopeptidases which excise the C peptide, thereby generating the mature form of insulin. Insulin and free C peptide are packaged in the Golgi into secretory granules which accumulate in the cytoplasm.

7 When the beta cell is appropriately stimulated, insulin is secreted from the cell by exocytosis and diffuses into islet capillary blood. C peptide is also secreted into blood, but has no known biological activity. The secreton of insulin

Synthesis of glucagon: n L cells of the intestine the transcription factors TCF-4 and Beta-catenin form a heterodimer and bind the G2 enhancer of the Proglucagon gene GCG, activating its transcription to yield Proglucagon mRNA and, following translation, Proglucagon protein. The prohormone convertase PC1 present in the secretory granules of L cells cleaves Proglucagon at two sites to yield mostly Glucagon-like Peptide-1 with a small amount of Glucagon-like Peptide-1 Glucagon-like Peptide is secreted into the bloodstream in response to glucose, fatty acids, insulin, leptin, gastrin-releasing peptide, cholinergic transmitters, beta-adrenergic transmitters, and peptidergic transmitters. The half-life of GLP-1 in the bloodstream is determined by Dipeptidyl Peptidase IV, which cleaves 2 amino acids at the amino terminus of GLP-1, rendering it biologically inactive.

synthesis of glucagon

8.The functin of Pancreatic hormons: The function of Pancreatic hormons are below A. Insulin: I. The function of insulin on the global human metabolism level include: o cellular intake of certain substances, most prominently glucose o increase of DNA replication and protein synthesis o modification of the activity of numerous enzymes II. The function of insulin on cells include: o Increased glycogen synthesis insulin forces storage of glucose in liver (and muscle) cells in the form of glycogen; lowered levels of insulin cause liver cells to convert glycogen to glucose and excrete it into the blood. This is the clinical action of insulin which is useful in reducing high blood glucose levels in diabetes. o increased fatty acid synthesis insulin forces fat cells to take in glucose which is converted to fatty acids; lack of insulin causes the reverse o increased esterification of fatty acids forces adipose tissue to make fats (ie, triglycerides) from fatty acid esters; lack of insulin causes the reverse o decreased proteinolysis forces reduction of protein degradation; lack of insulin increases protein degradation, o decreased lipolysis forces reduction in conversion of fat cell lipid stores into blood fatty acids; lack of insulin causes the reverse

9 o decreased gluconeogenesis decreases production of glucose from various substrates in liver; lack of insulin causes glucose production from assorted substrates in the liver and elsewhere o increased amino acid uptake forces cells to absorb circulating amino acids; lack of insulin inhibits absorption o increased potassium uptake forces cells to absorb serum potassium; lack of insulin inhibits absorption o arterial muscle tone forces arterial wall muscle to relax, increasing blood flow, especially in micro arteries; lack of insulin reduces flow by allowing these muscles to contract

B. Glucagon: Glucagon prevents the drop in blood glucose level (hypoglycemia), thereby helps in regulating blood-glucose level. Glucagon increases the blood glucose level by any of the following processes: o Glucagon is released when blood sugar levels drop too low. It stimulates the liver to convert glycogen to glucose, therefore increasing blood sugar levels. It is a hormone agonist .

10 o Its opposing hormone is insulin, an antagonist which is release when blood sugar levels climb too high. o Glycogenolysis breakdown of Glycogen. Glycogen is a polymer of glucose stored in the liver. The liver cells (hepatocytes) contain glucagon receptors. When glucagon binds to these receptors, the liver cells break-down glycogen to glucose monomers. The glucose is then released into the blood stream. o Gluconeogenesis synthesis of glucose from non-carbohydrate carbon substrates such as glycerol, lactate, glucogenic amino acids. o Lipolysis hydrolysis of lipids. It involves catabolism of triglycerides to free fatty acids and glycerol.

C. Somatostatin: The hormone somatostatin helps inhibit the release of insulin and glucagon. In addition, it also slows absorption of nutrients in the small intestine. 9 The disorders of panreas: Diseases of the pancreas, benign tumors, Carcinoma of pancreas, Cystic fibrosis, Diabetes, Pancreatitis, Acute pancreatitis,chronic pancreatitis, pancreatic pseudocyst etc 1. Acute pancreatitis: Causes: The most common cause of acute pancreatitis is the presence of gallstonessmall, pebble-like substances made of hardened bilethat cause inflammation in the pancreas as they pass through the common bile duct. Chronic, heavy alcohol use is also a common cause. Acute pancreatitis can occur within hours or as long as 2 days after consuming alcohol. Other causes of acute pancreatitis include abdominal trauma, medications, infections, tumors, and genetic abnormalities of the pancreas.

Symptoms:

11 Acute pancreatitis usually begins with gradual or sudden pain in the upper abdomen that sometimes extends through the back. The pain may be mild at first and feel worse after eating. But the pain is often severe and may become constant and last for several days. A person with acute pancreatitis usually looks and feels very ill and needs immediate medical attention. Other symptoms may include o A swollen and tender abdomen o Nausea and vomiting o Fever o A rapid pulse Severe acute pancreatitis may cause dehydration and low blood pressure. The heart, lungs, or kidneys can fail. If bleeding occurs in the pancreas, shock and even death may follow. Chronic pancreatitis: Causes: The most common cause of chronic pancreatitis is many years of heavy alcohol use. The chronic form of pancreatitis can be triggered by one acute attack that damages the pancreatic duct. The damaged duct causes the pancreas to become inflamed. Scar tissue develops and the pancreas is slowly destroyed. Other causes of chronic pancreatitis are o Hereditary disorders of the pancreas o Cystic fibrosisthe most common inherited disorder leading to chronic pancreatitis o Hypocalcaemiahigh levels of calcium in the blood o Hyperlipidemia or hypertriglyceridemiahigh levels of blood fats

12 Symptoms: Most people with chronic pancreatitis experience upper abdominal pain, although some people have no pain at all. The pain may spread to the back, feel worse when eating or drinking, and become constant and disabling. In some cases, abdominal pain goes away as the condition worsens, most likely because the pancreas is no longer making digestive enzymes. Other symptoms include o Nausea o Vomiting o Weight loss o Diarrhea Treatment: Treatment for chronic pancreatitis may require hospitalization for pain management, IV hydration, and nutritional support. Nasogastric feedings may be necessary for several Gallstones: Causes: o Gallstones occur when bile forms solid particles (stones) in the gallbladder. o The stones form when the amount of cholesterol or bilirubin in the bile is high. o Other substances in the bile may promote the formation of stones. o Pigment stones form most often in people with liver disease or blood disease, who have high levels of bilirubin. o Poor muscle tone may keep the gallbladder from emptying completely. The presence of residual bile may promote the formation of gallstones. Gallstones Symptoms:

13 Common symptoms of gallstones include the following: o Nausea and vomiting,fever, o Indigestion, belching, bloating, o Intolerance for fatty or greasy foods, and o Jaundice (yellowing of the skin or the whites of the eyes). o Warning signs of a serious problem are fever, jaundice, and persistent pain Pancreatic Cancer: Causes: The main recognized risk factors for pancreatic cancer include the following: o Smoking o Advanced age o Male sex - The male-to-female ratio of pancreatic cancer is 1.3:1. o Chronic pancreatitis - Inflammation of the pancreas, usually from excessive alcohol intake or gallstones o Diabetes mellitus Pancreatic Cancer Symptoms: The main symptoms of pancreatic cancer include the following: o Pain in the abdomen, the back, or both o Weight loss, often associated with the following: o Loss of appetite (anorexia) o Bloating

14 o Diarrhea or fatty bowel movements that float in water (steatorrhea) o Rarely may present with new diabetes in a person with weight loss and nausea o Jaundice (yellowing of the skin) Pancreatic Cancer Treatment: The optimal treatment of pancreatic Aden carcinoma depends on the extent of the disease. The extent of cancer can be divided into the following 3 categories: o Localized: The cancer is completely confined within the pancreas. o Locally advanced: The cancer has extended from the pancreas to involve nearby blood vessels or organs. o Metastatic: The cancer has spread outside the pancreas to other parts of the body. Tumor of pancears: An islet cell tumor may also be called a pancreatic endocrinetumor (PET), pancreatic neuroendocrine tumor, islet cell carcinoma, or pancreatic carcinoid.Islet cell tumors may or may not cause symptoms. There are different kinds of functional islet cell tumors. Islet cells make different kinds of hormones such as gastrin, insulin, and glucagon. Types of functional islet cell tumors include the following: o Gastrinoma: A tumor that forms in cells that make gastrin. Gastrin is a hormone that causes the stomach to release an acid that helps digest food. Both gastrin and stomach acid are increased by gastrinomas. When increased stomach acid, stomach ulcers, and diarrhea are caused by a tumor that makes gastrin, it is called Zollinger-Ellison syndrome. A gastrinoma usually forms in the head of the pancreas and sometimes forms in the small intestine. Most gastrinomas are malignant (cancer).

15 o Insulnoma: A tumor that forms in cells that make insulin. Insulin is a hormone that controls the amount of glucose (sugar) in the blood. It moves glucose into the cells, where it can be used by the body for energy. Insulinomas are usually slowgrowing tumors that rarely spread. An insulinoma forms in the head, body, or tail of the pancreas. Insulinomas are usually benign (not cancer). o Glucagonoma: A tumor that forms in cells that make glucagon. Glucagon is a hormone that increases the amount of glucose in the blood. It causes the liver to break down glycogen. Too much glucagon causes hyperglycemia (high blood sugar). Glucagonomas are often malignant. A glucagonoma usually forms in the tail of the pancreas. Most glucagonomas are malignant (cancer). o Other type of tumors: There are other rare types of functional islet cell tumors that make hormones, including hormones that control the balance of sugar, salt, and water in the body. These tumors include: o VIPomas, which make vasoactive intestinal peptide. VIPoma may also be called Verner-Morrison syndrome. o Somatostatinomas, which make somatostatin. 10. Conclution: After all we can say pancreas is an important organ in our body .The pancreas produces the body's most important enzymes. The enzymes are designed to digest foods and break down starches. The pancreas also helps neutralize chyme and helps break down proteins, fats and starch. Chyme is a thick semifluid mass of partly digested food that is passed from the stomach to the duodenum. If the pancreas is not working properly to neutralize chyme and break down proteins, fats and starch, starvation may occur. The pancreas is vital to good health. It is subject to a variety of problems, some of which result from the patient's own actions. There are now effective ways to diagnose pancreatic conditions and, in most cases, good treatment programs can be outlined by the physician.

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Reference http://digestive.niddk.nih.gov/ddiseases/pubs/pancreatitis http://endocrinehealth.blogspot.com/2009/05/hormones-produced-bypancreas.html http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pancreas.html http://www.gicare.com/diseases/Pancreatic-Disease.aspx http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin.html http://www.emedicinehealth.com/pancreatic_cancer/page3_em.htm http://www.gicare.com/diseases/Pancreatic-Disease.aspx http://www.medicinenet.com/pancreas_divisum/page2.htm