The document discusses the pancreas and its role in regulating blood glucose levels through the hormones insulin, glucagon, and somatostatin. It describes how insulin promotes glucose and fat storage while glucagon has the opposite effect of raising blood glucose. Diabetes results from insufficient insulin or insensitivity to its effects and can cause various health complications if not managed properly through diet, exercise, medication and insulin administration. The key roles of the pancreas and these hormones in maintaining blood glucose homeostasis are summarized.

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2. THE PANCREAS

4. TYPES OF TISSUES 1.Acini – secretes digestive juices 2.Islets of Langerhans- has 3 types of cells namely a. Alpha cells – 25% - secrete Glucagon b. Beta cells – 60% - secrete Insulin and Amylin c. Delta cells – 10% - secrete Somatostatin d. PP cells – secrete pancreatic polypeptide

5. INSULIN – Hormone Associated with Energy Abundance 1.Effect on Carbohydrate Metabolism A. Promotes Muscle Glucose Uptake and Metabolism -Storage of Glycogen in Muscle B. Promotes Liver Uptake, Storage and Use of Glucose Mechanisms: a. inactivates liver phosphorylase b. causes enhanced uptake of glucose from the blood by the liver cells (by increasing the activity of the enzyme glucokinase

6. C. increases activity of enzyme glycogen synthase , that promote glycogen synthesis - Glucose is released from the liver between meals Lack of insulin activates Phosphorylase , which causes splitting of glycogen into glucose phosphate - Insulin promotes Conversion of Excess Glucose into fatty Acids and Inhibits Gluconeogenesis in the liver

8. C. Lack of Effect of Insulin on Glucose Uptake and Usage by the Brain

9. 2. Effect on Fat Metabolism A.Insulin promotes Fat Synthesis and Storage - Storage of Fat n the Adipose Cells a. insulin inhibits the action of hormone-sensitive lipase b. insulin promotes glucose transport through the cell membrane into the fat cells

10. B. Insulin deficiency Causes Increase Metabolic Use of Fat causing a . Lipolysis of Storage Fat and Release of Free Fatty Acids b. Increase Plasma Cholesterol and Phospholipid c. Excess Usage of Fats during Insulin Lack Causes Ketosis and Acidosis

11. 3. Effect of Insulin on Protein Metabolism A. INSULIN PROMOTES PROTEIN Synthesis and Storage a. stimulates transport of amino acids into the cells ( valine, leucine, isoleucine, tyrosine, phenylalanine ) b. increases the translation of messenger RNA, forming new proteins c. increases the rate of transcription of DNA genetic sequences in cell nuclei d. inhibits catabolism of proteins e. depresses the rate of gluconeogenesis

12. B. Insulin Lack Causes Protein Depletion and Increased Plasma Amino Acids - protein wasting is one of the most serious of all effects of severe diabetes mellitus C. Insulin and Growth Hormone Interact Synergistically to Promote Growth INSULIN PROMOTES PROTEIN FORMATION AND PREVENTS DEGRADATION OF PROTEINS

13. MECHANISMS OF INSULIN SECRETION

16. CONTROL OF INSULIN SECRETION 1. Increased Blood Glucose Stimulates Insulin secretion

17. 2. Other Factors That Stimulate Insulin Secretion: a. Amino Acid – most potent are arginine and lysine - potentiates strongly the glucose stimulus for insulin secretion b. Gastrointestinal Hormones – Gastrin, Secretin, cholecystokinin, Gastric Inhibitory Peptide c. Other Hormones- Glucagon, Growth Hormone, Cortisol, Progesterone and Estrogen d. Autonomic Nervous System -Stimulation of the parasympathetic nerves to the pancreas can increase insulin secretion

18. Role of Insulin in “Switching” Between Carbohydrate and Lipid Metabolism GLUCAGON – a hormone secreted by the alpha cells of the islets of Langerhans when blood glucose concentration falls. Its important function is to increase blood glucose concentration thus is also called the Hyperglycemic Hormone.

19. Effects on Glucose Metabolism Major Effects 1. breakdown of liver glycogen (glycogenolysis ) 2. increased gluconeogenesis in the liver

20. Other Effects (when conc. rises above maximum normally found in the blood 1.activates adipose cell lipase- increasing fatty acids available to the energy system of the body 2.inhibits storage of triglycerides in the liver 3. enhances the strength of the heart 4. increases blood flow in some tissues, esp. kidneys 5. enhances bile secretion 6. inhibits gastric acid secretion

22. Regulation of Glucagon Secretion Increased Blood Glucose Inhibits Glucagon Secretion - the most potent factor that controls glucagon secretion - the effect of blood glucose conc. on glucagon secretion is in exactly the opposite direction from the effect of glucose on insulin secretion b. Increased Blood Amino Acids Stimulate Glucagon Secretion (especially alanine and arginine )

23. SOMATOSTATIN INHIBITS GLUCAGON AND INSULIN SECRETION Factors Related to Ingestion of Food Stimulate Somatostatin Secretion: 1. Increased blood glucose 2. Increased amino acids 3. increased concentrations of GI hormones 4. increased fatty acids

24. Inhibitory Effects of Somatostatin: Acts on the islets of Langerhans to depress the secretion of insulin and glucagon 2. decreases the motility of the stomach, duodenum and gallbladder

25. “ The Principal Role of Somatostatin” is to extend the period of time over which the food nutrients are assimilated into the blood

26. SUMMAR Y OF BLOOD GLUCOSE REGULATION Mechanisms: 1. The liver functions as an important blood glucose buffer system 2. Both insulin and glucagon function as important feedback control systems for maintaining a normal glucose concentration 3. Severe hypoglycemia stimulates the sympathetic nervous system 4. Growth hormone and cortisol are secreted in response to prolonged hypoglycemia, decreasing the rate of glucose utilization by most cells

27. Importance of Blood Glucose Regulation: Glucose is the only nutrient that normally can be used by the brain, retina and germinal epithelium of the gonads 2. Blood glucose should not too high (reasons) a. glucose exert a large amount of osmotic pressure in the ECF causing cellular dehydration b. high levels of blood glucose concentration causes loss of glucose in the urine c. causing osmotic diuresis by the kidneys d. long-term increase in blood glucose cause damage to many tissues, esp. blood vessels. Vascular injury leads to heart attack, stroke, end-stage renal failure and blindness

28. DIABETES MELLITUS It is a syndrome of impaired carbohydrate, fat, and protein metabolism caused by either insulin lack or decreased sensitivity of the tissues to insulin

29. Types of Diabetes Mellitus: 1. Type 1 Diabetes - also called insulin-dependent diabetes mellitus (IDDM), is caused by lack of insulin secretion. 2. Type II Diabetes – also called non-insulin dependent diabetes mellitus (NIDDM) , is caused by decreased sensitivity of target tissues to insulin. This reduced sensitivity to insulin is often referred to as insulin resistance

30. Type I Diabetes- Lack of Insulin Production by Beta cells of the Pancreas CAUSES: 1. Viral Infection or Autoimmune Disease – may be involved in the destruction of the beta cells 2. Heredity Usual onset of Type I diabetes occurs at about 14 years of age thus is often called Juvenile diabetes mellitus

31. Principal Sequelae: Increased blood glucose 2. Increased utilization of fats for energy and for formation of cholesterol by the liver 3. Depletion of the body’s proteins

32. Blood Glucose Concentration Rises to Very High Levels in Diabetes Mellitus Increased Blood Glucose Causes Loss of Glucose in the Urine Increased Blood Glucose Causes Dehydration Osmotic diuresis, polyuria, intracellular and extracellular dehydration, inceased thirst(polydipsia)

33. Chronic High Glucose Concentration Causes Tissue Injury: Blood vessels function abnormally resulting to inadequate blood supply to tissues leading to risk of heart attack , stroke, end- stage kidney disease , retinopathy and blindness , and ischemia and gangrene of the legs

34. Damage to tissues causing peripheral neuropathy (abnormal function of peripheral nerves, and autonomic nervous system dysfunction Hypertension ( secondary to renal injury) and arteriosclerosis (secondary to abnormal lipid metabolism)

35. Diabetes Mellitus Causes Increase Utilization of Fats and Metabolic Acidosis leading to coma and death As a result the patient develops severe metabolic acidosis leading to coma and death Arteriosclerosis – increased deposition of cholesterol in the arterial walls Kussmaul breathing - rapid and deep breathing – physiologic compensation in metabolic acidosis

36. Diabetes Causes Depletion of Body’s proteins - rapid weight loss and asthenia (lack of energy) despite of eating large amounts of food (polyphagia )

37. Type II Diabetes – Resistance to Metabolic Effects of Insulin more common than type I – to 90% of all cases of diabetes Onset occurs after the age of 30, often between 50 t0 60 years - referred to as Adult Onset Diabetes - related mainly to the increasing prevalence of obesity, the most important risk factor for type II diabetes in children as well as adults Obesity, Insulin Resistance and “Metabolic Syndrome” Usually Precede Development of Type II Diabetes

38. Features of Metabolic Syndrome Obesity, especially accumulation of abdominal fat Insulin resistance Fasting hyperglycemia Lipid abnormality such as increased triglycerides and decreased blood high – density lipoprotein – cholesterol hypertension

39. Other Factors That cause Insulin Resistance and Type II Diabetes Polycystic Ovary Syndrome (PCOS) Excess formation of glucocorticoids (Cushing Syndrome) or growth hormone (acromegaly) Development of Type II Diabetes During Prolonged Insulin Resistance

42. Physiologic Diagnosis of Diabetes Mellitus 1. Urinary Glucose 2. Fasting Blood Glucose and Insulin Levels - in the early fasting blood glucose level is normally 80 to 90 mg/100 ml -110 mg/100 ml to be the upper limit

43. FBS above this value indicates diabetes mellitus - type I diabetes – plasma insulin levels are very low or undetectable during fasting and after a meal type II diabetes – plasma insulin concentration is higher than normal 3. Glucose Tolerance Test 4. Acetone breath

44. TREATMENT OF DIABETES : A.Type I diabetes –administer enough insulin B. Type II diabetes dieting and exercise drugs

45. Insulinoma – Hyperinsulinism - occurs from an adenoma of an islet of Langerhans - insulin shock and hypoglycemia - as blood glucose level falls into the range of 50 to 70 mg/dl the CNS becomes excitable leading to hallucinations, extreme nervousness, trembles all over, breaks out in a sweat

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