Pancreas and ilets of langerhane

A Study of Pancreas and ilets of langerhane

1. By Dr.A.Krishnamoorthi, Assistant Professor in Zoology, Arignar Anna Government Arts College, Namakkal ,Tamil Nadu, India. Pancreas and ilets of langerhane

2. PANCREAS AND ILETS OF LANGERHANE Pancreas and ilets of langerhane The pancreas is a dual function organ situated in the loop of the stomach and duodenum. It has both exocrine and endocrine glands . In adults, it is about 12–15 centimetres long ,  lobulated , and salmon-coloured in appearance. Anatomically, the pancreas is divided into a  head ,  neck ,  body , and  tail . The pancreas stretches from the inner curvature of the duodenum, where the head surrounds two blood vessels, the superior mesenteric artery, and vein. The body of the pancreas travels from the head, separated by a short neck. The neck is about 2  cm wide, and sits in front of the portal vein. The body is the largest part of the pancreas, and mostly lies behind the stomach.

3. The pancreas narrows towards the tail, which sits next to the spleen .   It is usually between 1.3–3.5  cm long, and sits between the layers of the ligament between the spleen and the left kidney. The exocrine gland that histologically composed of pancreatic acini , which are serous in character and are lined by cuboidal epithelium. Acini synthesis digestive enzymes called pancreatic juice that drain into the duodenum through the pancreatic ducts. Two ducts, the main pancreatic duct and a smaller accessory pancreatic duct, run through the body of the pancreas, joining with the common bile duct.  

4. Structure of pancreas

5. Anatomy of the Endocrine Pancreas The endocrine portion of the pancreas contains many small clusters of cells called  islets of Langerhans . The cells are ovoid bodies, 75 – 175 µm (0.1mm) diameters in size. They are scattered throughout the pancreas, but more numbers in the tail of the pancreas. A healthy adult human has 3 million islets and form 1 to 2% of the mass of the pancreas. Each is separated from the surrounding pancreatic tissue by a thin fibrous connective tissue capsule which is continuous with the fibrous connective tissue that is interwoven throughout the rest of the pancreas

6. Pancreatic islets have five cell types ,each of which produces a different endocrine product: Alpha cells  (A cells) found 20% of the total islets cells. They are large granular cells secrete the hormone  glucagon . Beta cells  (B cells) are the most abundant of the islet cells found 70%. They are smaller granular cells produce  insulin and Amylin . Delta cells  (D cells) are found 5 – 8% and secrete the hormone  somatostatin , which is also produced by a number of other endocrine cells in the body. PP cells (gamma cells or F cells) found less than 5% and producing  pancreatic polypeptide. Epsilon cells found 1% producing  ghrelin .  

7. The different cell types within an islet are not randomly distributed - beta cells occupy the central portion of the islet and are surrounded by a "rind" of alpha and delta cells. Islets have rich blood supply , they receive about 10 to 15% of the pancreatic blood flow. They allowing their secreted hormones enter to the blood and pass first to the liver via portal circulation before reaching the systemic circulation. Additionally, they are innervated by parasympathetic and sympathetic neurons, and nervous signals clearly modulate secretion of insulin and glucagon.

8. Islets of Langerhans showing different types of cells

9. . Pancreatic Hormones and Their Function The pancreas is a composite organ, which has exocrine and endocrine functions. The endocrine portion is arranged as discrete islets of Langerhans , which are composed of five different endocrine cell types (alpha, beta, delta, epsilon, and upsilon) secreting at least five hormones including glucagon , insulin, somatostatin , ghrelin , and pancreatic polypeptide, respectively

10. .   Insulin Insulin is a peptide hormone secreted by the Beta cells of islets of the pancreas. It made up of two polypeptides A and B chain that are held together by a disulphide bond . The A chain contains 30 amino acids and the B chain contains 21 amino acids. So it has 51 amino acids with a molecular weight of 6000 Da. In A chain N-terminal amino acid is glycine and C- treminal amino acid is asparagines. In B-chain N-terminal amino acid is phenyl alanine and C-terminal amino acid is threonine . Both the chains are held together by two S-S linkage Cys-7 and Cys-20 of A chain are jointed to Cys-7 and Cys-19 of B chain respectively. In addition the A chain carries an intra chain S-S linkage between Cys-6 and Cys-11.

11. Biosynthesis of insulin: Insulin is a small peptide hormone that is formed directly by the genetic translation (gene) via insulin mRNA. A single-chain polypeptide insulin precursor called preproinsulin is synthesized in the ribosome of the rough endoplasmic reticulum membrane of the beta cells of the islets. It has 109 amino acids with a molecular weight of 11,500 Da. Pre- proinsulin synthesized is transferred to lumen of the rough endoplasmic reticulum cisternae . From which in N-terminal 23 amino acids are split by an enzyme called signal pepdidase and become folded and linked by disulphide bond to form proinsulin . It has 86 amino acids. Molecular weight is 9000.

12. 3 . The proinsuline containing small vesicle are detached from E.R and fused with the cisternae of Golgi body. In the Golgi body, proinsulin is acted upon by a trypsin like protease enzyme which hydrolyzes the peptide chain at two sites. So that an inactive connective C peptide is removed (31 amino acids) and two active peptide chains are left which forms A and B chain. 4. A carboxypeptidase B like enzyme split the C-terminal basic amino acid from both chain. Arg 63, Lys 62 from A-chain and Arg-31, Arg-32 from B chain to form an active insulin (see fig 5.3, b). The insulin are packaged and stored in the granules that originated from the Golgi body of the beta cells. The granules are moved to the peripheral region of the cells. In response to the stimulus, Insulin is secreted from the cell by exocytosis and diffuses into islet capillary blood. C-peptide is also secreted into the blood in a 1:1 molar ratio with insulin. Although C-peptide has no established biological action, it is used as a useful marker for insulin secretion.

13. a. Biosynthesis of insulin, b. amino acids sequences in insulin

14. The average daily secretion is about 2 mg (50 units). One unit of insulin is defined as 1/3 of the amount of insulin that will lower the blood sugar level of a 2 kg fasting rabbit to the convolution value in 3 hours. The total insulin content of the pancreas is about 200 to 250 units. Insulin secretion is continuous, but the rate of secretion is influenced by a variety of factors. The half life of insulin is about 5 minutes. It is metabolized chiefly in liver and kidney. About half is inactivated during first pass in the liver by the enzyme insulin glutathione transhydogenase which cleaves the molecule into A and B chains. The rest are inactivated in the kidney and other tissues by enzymes insulinases .

15. Regulation of its secretion: Plasma glucose level (70 -110mg/dl) is the main regulator of insulin secretion. The change in the concentration of plasma glucose that occurs in response to feeding or fasting is the main determinant of insulin secretion. Modest increases in plasma glucose level provoke a marked increase in plasma insulin concentration. Glucose is taken up by beta cells via glucose transporters (GLUT2). The subsequent metabolism of glucose increases cellular adenosine triphosphate (ATP) concentrations and closes ATP-dependent potassium (KATP) channels in the beta cell membrane, causing membrane depolarization and an influx of calcium.

16. Increased calcium intracellular concentration results in an increase of insulin secretion. Thus there is a feedback mechanism that exists between the blood glucose level and the secretion of insulin by the beta cell Increased plasma amino acid and free fatty acid concentrations induce insulin secretion as well. Glucagon is also known to be a strong insulin secretion.

17. Physiological functions: Insulin’s main actions are Insulin plays an important role to keep plasma glucose value within a relatively narrow range (70-110mg/dl) throughout the day (glucose homeostasis) under varying conditions of food intake, fasting, exercise, etc,. In the liver, insulin promotes glycolysis and storage of glucose as glycogen ( glycogenesis ), as well as conversion of glucose to triglycerides. In muscle, insulin promotes the uptake of glucose in all cells except brain, renal and intestinal mucosa and its storage as glycogen. In adipose tissue, insulin promotes uptake of glucose and its conversion to triglycerides for storage. Since insulin promotes protein synthesis by increasing entry of amino acids into the cells and makes availability of energy from increased oxidation of glucose, it has a promising role in the growth of an organism .

18. . . Clinical Significance: Diabetes Mellitus (DM) is a chronic disease that occurs when the pancreas cannot produce enough insulin, or the body cannot effectively utilize insulin, which results in high glucose plasma level ( hyperglycemia ). Nearly 10% of Indian population have this disease. Diabetes mellitus means excessive excretion of sweet urine.

19. Diabetes Mellitus (DM) have the following symptoms Poly- uria : excrete more volume of urine. As the blood glucose level exceeds the renal threshold (180 mg/dl) glucose appears in the urine ( glycosuria ) that prevent the reabsorption of water in the proximal tubules resulting excrete large volume of water. Polydipsia : stimulate thirsty and drinking more water. Dehydration and loss of electrolytes in the cells stimulate thirst and cause polydipsia . Polyphagia : intake of more food. the high glucose level blood enter in to the ventromedial nucleus of hypothalamus inhibits the satiety centre of brain to stimulate increased appetite and food intake but weight loss.

20. There are two common types of DM that account for the majority of cases: type 1 and type 2. Type 1 DM It is a chronic autoimmune disease in which the beta cells of islets of the pancreas are destroyed resulting in insulin deficiency. It is also called Insulin Dependent Diabetes Mellitus (IDDM). Type-1 diabetes occurs early in the life (5 -25years) so it is called juvenile onset diabetes.

21. Pathophysiology : It is not entirely understood yet, but it is caused by a combination of events in genetically susceptible individuals. Three mechanisms lead to islet cell destruction: genetic susceptibility, autoimmunity, and environmental insult(s). A virus or allergen (environmental insults) in genetically susceptible individuals induces the production of autoantibodies to Beta cells of the islets of the pancreas. This autoimmune reaction creates autoreactive T cells that destroy beta-islet cells and cause loss of insulin secretion. The major symptoms are polyuria , polydipsia and glycosuria . IDDM disease response to insulin injection. IDDM requires insulin therapy and careful, lifelong control of the balance between dietary intake and insulin dose.

22. Type 2 DM or non insulin dependent diabetes mellitus (NIDDM) It occurs on the later age and is referred to as maturity onset diabetes. It is a progressive disease that develops due to a in insulin sensitivity that causes hyperglycemia . The development and rate of progression of T2continued decline in beta-cell function and/or due to a defect D are influenced by both genetic and environmental factors, such as obesity and physical inactivity.

23. Pathophysiology : Beta-cell dysfunction manifests in different ways: (1) reductions in insulin release, (2) changes in pulsatile insulin secretion, (3) an abnormality in the efficiency of proinsulin to insulin conversion, and (4) reduces the release of amylin . Insulin resistance is present in most patients with T2D. Insulin resistance is characterized by higher than expected plasma glucose level with the prevailing plasma insulin secretion. In patients with T2D insulin, stimulation fails to induce normal GLUT4 protein translocation to the sarcolemma in skeletal muscle membrane. Also, excessive production of free fatty acids. Production of ketone bodies by the accumulation of acetyle – CoA .  

24. 2.Amylin (diabetes-associated peptide) Amylin is a peptide hormone secreted by the Beta cells of islets of the pancreas. It is co-secreted with insulin in response to caloric intake (feeding state). 

25. Physiological functions: It suppresses glucagon secretion from the alpha cells of the islets in the pancreas via paracrine interaction between beta cells and alpha cells. Amylin also slows gastric emptying which delays absorption of glucose from the small intestine into the circulation. Also, it stimulates the satiety centre of the brain to limit food consumption.

26. 3.Glucagon Glucagon is a protein hormone. It is secreted by the Alpha cells of islets of the pancreas. It is a single chain polypeptide having 29 amino acids. Its molecular weight is about 3485 Da. There are only fifteen different amino acids in the molecule. Amino acid sequences has been determined. Histidine is the N-terminal amino acid and threonine is the C-terminal. It is also known as hyperglycaemic glycogenolytic factor (HGF). Because, it is primarily concentrate with increases in blood glucose level.

27. Synthesis: The initial gene product is the mRNA encoding preproglucagon . A peptidase removes the signal sequence of preproglucagon during translation of the mRNA in the rough endoplasmic reticulum to yield proglucagon . Proteases in the alpha cells subsequently cleave the proglucagon into the mature glucagon molecule. The plasma half life of glucagon is about 5 – 10 minutes. It is inactivated mainly in the liver, but also kidney and other tissues.

28. Regulation of its secretion: The amino acids released by digestion of a protein meal appear to be the main determinant of glucagon secretion. High plasma glucose inhibits while hypoglycaemia increases glucagon secretion. Free fatty acids and ketone bodies inhibits glucagon secretion.  

29. Physiological functions: Glucagon acts exclusively on the liver to antagonize insulin effects on hepatocytes . It enhances glycogenolysis and gluconeogenesis in hepatocyte cells so that increase in blood glucose level.biiut does not stimulate muscles glycogenolysis . It also promotes lipolysis (oxidation of fat), which can lead to the formation of ketone bodies. It also stimulates secretion of insulin, growth hormone, pancreatic somatostatin and hepatic bile secretion. In pharmacological doses it increases myocardial contractility.

30. Clinical significance : Hypoglycaemia is a syndrome characterized by low plasma glucose. During the first week after birth, the infant is hypoglycaemic its plasma glucose concentration is less than 25 mg/dl of blood. In adult, symptoms occur in acute or chronic. If the low plasma glucose occurs rapidly, symptoms of sweating, shakiness, trembling, weakness and anxiety are produced. If the reduction in plasma glucose occurs slowly, headache, irritability, lethargy and other central nervous system symptoms predominate. Prolonged ingestion of ethanol and other drugs may damage liver cells and cause fasting hypoglycaemia. Adrenocortical insufficiency and hypopituitarism are also associated with hypoglycaemia.

31. 4.Somatostatin Somatostatin is a protein hormone secreted by the Delta cells of the islets of the pancreas, hypothalamus and D cells of gastric glands . Two form of somatostatin are synthesized. They are referred to as SS-14 and SS-28 . Both form of somatostatin are generated by proteolytic cleavage of prostomatostatin . SS-14 is the predominant form secreted by the delta cells of islets and hypothalamus, whereas the intestine D cells secrete SS-28. SS-14 has 14 amino acid residues and SS-28 has 28 amino acids residues.

32. Regulation of its secretion: Glucagon stimulates somatostatin secretion via paracrine interaction between alpha cells and delta cells of the islets of the pancreas.

33. Physiological functions: Somatostatin inhibits the secretion of multiple hormones, including growth hormone, insulin, glucagon, gastrin , vasoactive intestinal peptide (VIP), and thyroid-stimulating hormone. Somatostatin act on pituitary gland to inhibits secretion of growth hormone. It diffusing into neighbouring islets cells to inhibit secretion of insulin, glucagon and pancreatic polypeptides. Somatostatin secreted by the gastro intestinal tract inhibits secretion of many other intestinal hormones such as gastin , cholecystokinin , vasoactive intestinal peptides (VIP). It also inhibits pancreatic exocrine secretion, bile secretion and motility. It reduces smooth muscles contraction in gall bladder contraction, oesophagus contraction and blood flow within the intestine.

34. 5.Ghrelin Ghrelin is a polypeptide secreted by the Epsilon cells of the islets of the pancreas, endocrine cells in the stomach and hypothalamus.   Ghrelin inhibits the secretion of insulin from Beta cells of the islets of the pancreas via paracrine interaction between delta cells and beta cells of the islets of the pancreas. It also stimulates appetite and growth hormone secretion

35. 6.Pancreatic Polypeptide (PP) Pancreatic polypeptide is secreted from upsilon (F) cells of the islets of the pancreas. It is a single polypeptide chain containing 36 amino acids. It inhibits pancreatic and biliary secretion, increasing gastric emptying time and motility of small intestine. It relaxes pyloric and ileocolic sphincters. Dietary intake of nutrients alters the secretion of the pancreatic polypeptide. Its secretion is increased by fasting, hypoglycaemia, exercise protein meals and some gastro intestinal hormones and decreased by somatostatin .

36. .