The Pancreas

The Pancreas The pancreas is a vital organ, without it, unless an individual is give insulin shots, the person wont survive. There are different populations of cells in the pancreas: A cells produce glucagon, B cells produce insulin, D cells produce somatostatin and F cell produce pancreatic polypeptide. The metabolic effects of pancreatic hormones are a balance between anabolism (insulin) and catabolism (glucagon). Insulin is synthesised as pre-proinsulin. In the ER it become proinsulinand is later divided into insulin and peptide C in the secretory vesicles. Peptide C is used to measure glucose tolerance by the body since it is more stable (longer T1/2) and is hence more easy to measure than insulin. Since insulin is a peptide it has a cell surface receptor and it itself does not cross the membrane. The receptor is made up of 2 α and β subunits, which dimerizes when insulin binds, to activate a tyrosine kinase. Mutations of genes on chromosome 11 that codes for the insulin receptor gives rise to Type I diabetis. Insulin as a molecular weight if 5808 Da and has a half life of 5 minutes. The insulin given to patients has been manipulated to have a longer half-life. 80% of insulin is broken down in the liver and kidneys. However in diabetic patients, the patient’s live and kidneys are effected, resulting in insulin that takes a longer time to be broken down and so has a longer chance of acting. The glucose taken in from the GIT after a meal may be used for pyruvate and ultimately ATP production by tissues or may be stored in the liver as glycogen: which acts as a reservoir for glucose. Glucose is required by all peripheral tissues such as the liver, GIT, adipose tissue, skin and erythrocytes. Of particular importance is the CNS which is very sensitive to glucose concentrations and their could be a loss of consciousness or even death in cases of hypoglycaemia. Insulin has a rapid effect on the uptake of glucose, amino acids and K + by insulin sensitive cells. The intermediate effects are protein synthesis from amino acids(reason why abused by bodybuilders), inhibition of protein breakdown. This is the reason why insulin deficiency causes weight loss. Insulin also causes activation of glycogen synthase and glycolytic enzymes, inhibition of phosphorylase and gluconeogenic enzymes. The delayed effects are the increased production of mRNAs for lipogenic and other enzymes. There are two catagories of glucose transporters: active transporters and facilitated diffusion type. The latter consist of 5 types: GLUT-1 for basal glucose uptake: many organs have this including the brain, GLUT-2: in B cells, liver and intestine, GLUT-3 is also a basal type of transporter. GLUT-4 is insulin stimulated and GLUT-5 is involved in dietary absorption in the jejunum. If this organ is removed, more insulin will reach the large intestine, which carries with it water and hence causes diarrhea. Secretion of insulin is stimulated by, increased glucose concentration, increased non-glucogenic amino acids, intestinal hormones such as gastrin, secretin and GIP, which are secreted when a person eats. Glucagon is also stimulatpry to insulin synthesis. Theophylliline a B agonist used in asthmatics, also increases

insulin sectetion. This sould be given with care to diabetic who already take insulin to control their diabetis since this added insulin may result to hypoglycaemia. Sulfonylureases also stimulate insulin secretion by acting on pancreatic cells. On the other hand thiazide diuretics used for hypertension can unmark diabetis as it inhibits insulin secretion and the same applies to phenytoin which is used for the treatment of epilepsy. Insulinnegatively feedbacks itself, since it is also an inhibitor of further insulin release. Glucagon like insulin is synthesised as a pre-prohormone. It is composed of major proglucagon factors : glucagonlike polypeptides 1 and 2, the former in diabetics suppresses glucagon secretion. It is degraded in the liver. It is a G protein coupled receptor with both inhibitory and G stimulatory types. These will modulate cAMP and protein kinase A leading to activation pf phosphorylases and glycogenolysis in the liver. Phospholipase C increases intracellular calcium concentrations to increase glycogenolysis. The liver will brak down glycogen and glucose is catabolised to form energy for muscles and other tissues, under the influence of glucagon. If glucose is not present, adipose tissue is broken down into fatty acids which can be used for energy in all the tissue except in the CNS where fatty acids have to be converted into ketone bodies in order to be used. Glucagon secretion is inhibited by glucose, somatostatin, secretin, free fatty acids, insulin and phenytoin. Stimulants inclyde stress, amino acids, esp those that lead to glucose synthesis and cortisol (a stress hormone).