Anatomy of Pancreas:Exocrine and Endocrine functions The Pancreas as an endocrine gland- Exocrine and Endocrine functions exist!! Pancreatic juice contains enzymes for digesting all three major Below the stomach is the pancreas consisting of a: head, types of food: proteins, carbohydrates, and fats. It also contains body and a tail. It is considered an accessory gland in large amounts of bicarbonate ions to neutralize the acid chyme digestion due to its exocrine function. emptied by the stomach into the duodenum. The pancreas produces enzymes that break down all 1) Proteolytic enzymes – trypsin, chymotrypsin (both make smaller peptides), categories of food stuffs. These enzymes are then carboxypolypeptidase (breaks off amino acids from the carboxyl ends of peptides), ribonuclease, and deoxyribonuclease (last two split two types of nucleic acids – emptied into the small intestine along with bile from the ribonucleic acid and deoyxribonucleic acid). liver. The exocrine product of the pancreas is called 2) Carbohydrate digestive enzymes – pancreatic amylase (hydrolyzes starches, pancreatic juice and it passes to the small intestine via glycogen and most other carbs except cellulose) the pancreatic duct. 3) Fat digestive enzymes – pancreatic lipase ( hydrolyzes neutral fat into fatty acids Pancreas has 2 portions: and monoglycerides), cholesterol esterase (hydrolyzes cholesterol esters) and phospholipase(splits fatty acids from phospholipids). 1) Acinar cells – full of RER-containing digestive enzymes (proteins) and other juices. This represents the exocrine portion of the pancreas since the contents empty into a duct. 2) Islets of Langerhans – actually are the endocrine portion of the pancreas because they release hormones into the bloodstream without a duct. When each of these proteolytic enzymes are synthesized in Exocrine portion acinar cells secrete digestive enzymes into pancreatic cells, they are found in inactive forms such as - the small intestine along with bicarbonate (HCO3 )which trypsinogen, chymotrypsinogen, and procarboxypolypeptidase. neutralizes the gastric acid produced by the stomach. Two ducts: 1) Primary is the Duct of Worsung which unites They only become activated after being secreted into the intestinal tract. Important not to become activated until these proteolytic enzymes have been secreted into the with the common bile duct, and 2) secondary is the Duct intestine for the trypsin and others would digest the pancreas itself. The same cells of Santorini. that make trypsin secrete another substance called trypsin inhibitor simultaneously. It prevents activation of trypsin both inside the secretory cells and in the acini and ducts Regulation of these pancreatic juices is controlled by 2 of the pancreas. Trypsin activates most of these other enzymes so the TI prevents their hormones not released from the pancreas but released by activation until out of the pancreas. the intestinal mucosa cells of the small intestine: Acute pancreatitis – seen commonly clinically. This is where the pancreas becomes 1) Secretin – released due to the presence of acid chyme in severely damaged or a duct becomes blocked and large quantities of pancreatic the small intestine. Chyme is partially digested food that secretion become pooled in the damaged areas of the pancreas. The TI is overwhelmed leaves the stomach. Bicarbonate is released as a result of by the quantity and as a result the pancreatic enzymes become activated and literally digest the entire pancreas within a few hours and seen in the condition as acute secretin trying to neutralize acid chyme. pancreatitis. It is often lethal and if not, leads to a lifetime of pancreatic problems. Would see an increase in amylase to indicate problems with pancreas. 2) Cholecystokinin – released due to presence of partially digested foods in S.I. It causes the gall bladder to contract 1 And the Sphincter of Oddi to relax. The sphincter of Oddi is the sphincter that separates the common bile duct and Pancreatic hormones: pancreatic duct from the small intestine. So by relaxing it, Somatostatin and pancreatic polypeptide bile and pancreatic juices can be dumped into the small intestine. That is the exocrine portion of the pancreas. 1) Somatostatin – a)inhibits both glucagon and insulin secretion; b)inhibits motility of the stomach, duodenum and the GB; c) decreases both secretion and absorption Endocrine function of the pancreas - of the GI tract. Sources are hypothalamus and pancreatic delta cells. What stimulates its secretion: Between exocrine cells are cluster of cells called the Islets of Langerhans that contain actually 4 types of cells: a) ↑ blood glucose b) ↑ blood amino acids 1) Alpha cells – produce glucagon (hormone); 25% total cells c) ↑ blood fatty acids 2) Beta cells – site of insulin synthesis and secretion; 60% d) ↑ GI hormones form the upper GI tract 3) Delta cells –produce somatostatin (inhibits GH);10% What inhibits its secretion: a) insulin; b) catecholamines 2) Pancreatic polypeptide - released from the PP cells in the Islet, and function is 4) PP cells – least common; secretes pancreatic relatively unknown but it may play a role in certain GI functions. polypeptide;<5% Pancreatic hormones: Endocrine portion of the pancreas develops before the exocrine portion (Acinar cells). This is very important in the history Insulin and Glucagon of diabetes. Let’s look at some historical moments to Insulin –it is a small protein composed of two amino acid prove this. chains. When they are split apart, it is nonfunctional. It is a) Aristotle –found some patients that had flies and ants attracted to their urine made by the beta cells of the pancreas. and he realized they had “sweet” urine. He gave it the name “diabetes mellitus” due to the glycosuria. Starts as insulin preprohormone on ribosomes of endoplasmic b) Von Merring and Minkowski, 1900’s, - they were the first to show the reticulum but then is cleaved in the ER to form a relationship between diabetes and the pancreas. They removed the pancreas proinsulin. Most of this is further cleaved in the Golgi from a dog and he developed diabetes. 1st to implicate the organ to disease. apparatus to form insulin before being packaged into c) Schultze – He ties off pancreatic ducts and found more to pancreas than just secretory granules. About one sixth of the secreted diabetes. No glycosuria but digestive problems. product is still in the form of proinsulin which has no d) Banting and Best, 1920’s – professor and grad student. They tried to relieve the symptoms of diabetes by injecting a dog with ground up pancreatic extract insulin activity. Once insulin secreted, it has a half-life of into diabetic dogs. Didn’t work. Why??? Best, however, came in alone one about 6 minutes so that it is mainly cleared in 10-15 night and repeated the experiment but he used fetal pig pancreas extract and he minutes from circulation. Some binds receptors of target cured the diabetic dog. Therefore, he proved that the endocrine portion of the pancreas develops embryologically before the exocrine. Why??? Banting and cells while the rest is degraded by liver and some in McCloud shared the Nobel prize for this even though Best figured it out!!! kidneys. Factors Influencing Insulin Secretion, cont. Factors Regulating Insulin Secretion 3) Fatty acids and ketone bodies – increases insulin secretion 1) Hi plasma glucose levels – insulin is secreted to return glucose levels back to normal. This is the biggest negative feedback to 4) Hormones: a) GI hormones – gastrin, secretin, regulate insulin secretion!!!! Insulin increases in 3 stages: a) 1st cholecystokinin, and gastric inhibitory peptide all cause a 5 minutes after the initial challenge is from preformed beta cell moderate increase in insulin. Released after eating a meal in stores then decreases halfway back to normal; b) 20 min. from “anticipation” of an increase in preparation for the glucose the initital challenge and lasts for 1 – 2 hours is newly and amino acids to be absorbed from the meal. These also synthesized insulin and is higher than the initial release of double the rate of insulin secretion following an average insulin; c) days from initial challenge is from hypertrophication meal. b) Others – glucagon, GH, cortisol, to of beta cells and could destroy them or burn them out. lesser extent progesterone and estrogen. These either increase insulin secretion or potientiate glucose stimulus for insulin 2) Hi plasma amino acids – just after a hi protein meal, arginine secretion. Importance is that if any one of these has prolonged and lysine stimulate the beta cells to increase insulin secretion. secretion in large quantities then the beta cells could be Amino acids and glucose together potientiate the effects on overworked and exhausted to eventually cause diabetes. insulin. Increased insulin enhances entry of these amino acids Pharmacological doses of any of these could lead to diabetes into cells so lowers the amino acids and promotes protein especially if the person has a diabetic tendency. synthesis. 2 Effect of Insulin on Carbohydrate Effect of Insulin on Carbohydrate Metabolism, cont. Metabolism 1) Promotes glucose uptake into LIVER to be stored as 3) Enhances conversion of excess liver glucose into fatty acids glycogen. This occurs almost immediately after glucose is which are then transferred into adipose tissue and deposited increased and insulin is released. This is for the times as fat. between meals when glucose levels fall and at that time, glycogen is then split back into glucose and released back into 4) Insulin inhibits gluconeogenesis (in the liver). the blood to bring glucose levels back to normal. 5) Insulin inhibits glycogenolysis. 2) Insulin stimulates an increase in glycogenesis especially in Summary: Lowers blood glucose; The only hormone to do skeletal muscle and liver and glucose uptake by the liver cells so!! all with the net effect of increasing the amount of glycogen stored in the liver. Effect of Insulin on Fat Metabolism Insulin increases the utilization of glucose by most of the Effects of Insulin on Protein Metabolism body’s tissues which automatically decreases the use of fat so serves as a “fat sparer”.