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METABOLISM & PANCREAS

METABOLISM & PANCREAS. George Liapakis , PhD. Metabolism . Chemical reactions that occur within the cells of our body . Degradation , synthesis, and transformation of three energy-rich organic molecules . Proteins Carbohydrates Fats . . Food Large nutrient molecules .

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METABOLISM & PANCREAS

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  1. METABOLISM & PANCREAS George Liapakis, PhD

  2. Metabolism Chemical reactions that occur within the cells of our body Degradation, synthesis, and transformation of three energy-rich organic molecules Proteins Carbohydrates Fats.

  3. Food Large nutrient molecules Digestion Large nutrient molecules are broken down into smaller absorbable nutrient molecules into the gastrointestinal tract. Fat Proteins Carbohydrates Proteins Carbohydrates Dietary fats

  4. Digestion Proteins Carbohydrates Dietary fats (or triglycerides) Amino acids Glucose, Free fatty acids.

  5. AFTER ABSORPTION Glucose Gluconeogenesis Amino acids 1 Production of energy 2 Fatty acids The conversions, 1 and 2 allow all three categories of food stuff to be used as energy sources, if needed.

  6. Glucose is the major energy source • In the absence of dietary glucose, fatty acids can be used as metabolic fuels by tissues (muscles) thus sparing glucose for brain. Dietary Glucose Blood Glucose Production of energy in tissues Fatty acids

  7. In the absence of dietary glucose, amino acids (from breakdown of proteins) can be converted to glucose (to be used by brain) • LAST CHOICE Dietary Glucose Amino acids Blood Glucose Gluconeogenesis CATABOLISM Protein Breakdown of large molecules to smaller: CATABOLISM

  8. In the absence of dietary glucose, GLYCOGEN (storage form of glucose) can be converted (GLYCOGENOLYSIS) to glucose (to be used by brain). • FIRST CHOICE Dietary Glucose Blood Glucose Glycogenolysis CATABOLISM GLYCOGEN

  9. In the absence of dietary glucose the fatty acids (used as metabolic fuels by all tissues except brain) come from the breakdown of the fat of our body (stored in adipocytes), thus sparing glucose for brain. • FIRST CHOICE Production of energy in tissues Fatty acids Dietary Glucose CATABOLISM FAT

  10. How Fats, Glycogen and Proteins are formed ?

  11. Fats, Glycogen and Proteins are formed from small nutrient molecules Dietary Fats Dietary Proteins Dietary Glucose AFTER DIGESTION & ABSORPTION Excess amino acidsno needed for protein synthesis Gluconeogenesis Glucose Amino acids Fatty acids Filled up glygogen stores ANABOLISM Buildup of large molecules from smaller ones Glucogenesis PROTEINS Muscles other tissues FAT Triglycerides Adipose tissue GLYCOGEN LIVER STORAGE FORMS

  12. During a period of fasting Amino acids Fatty acids Glucose PROTEINS Muscles, other tissues FAT Triglycerides Adipose tissue They breakdown to amino acids, which are converted to glucose that is used by the brain LAST CHOICE Enough triglyceride is stored to provide energy for about 2 months GLYCOGEN LIVER Small energy reservoirwith less than a day’s energy needs FIRST CHOICE

  13. Processes that take place after a meal and between meals. • Absorptive state • After a meal ingested nutrients are absorbed and enter the blood. • An average meal is completely absorbed in about 4 hours • Post-absorptive (or fasting) state • After 4 hours from a meal and before a second meal no nutrients are absorbed from the digestive tract.

  14. Absorptive state • Blood glucose is abundant • Glucose is the major energy source • Extra glucose is stored Glucose Fatty acids • Very little of the absorbed fat is used for energy • Fatty acids and amino acids are stored Amino acids

  15. Absorptive state: Extra glucose, fatty acids and amino acids are stored Dietary Fats Dietary Proteins Dietary Glucose AFTER DIGESTION & ABSORPTION Excess amino acidsno needed for protein synthesis Gluconeogenesis Glucose Amino acids Fatty acids Filled up glygogen stores ANABOLISM Buildup of large molecules from smaller ones Glucogenesis PROTEINS Muscles other tissues FAT Triglycerides Adipose tissue GLYCOGEN LIVER STORAGE FORMS

  16. Post-absorptive (or fasting) state Glucose • Storage forms of nutrient molecules (glycogen, triglycerides, proteins) are broken down to glucose, fatty acids, amino acids (used for gluconeogenesis) • Glucose for brain, fatty acids for other tissues Amino acids Fatty acids

  17. During a period of fasting: Breakdown of storage forms of nutrients Amino acids Fatty acids Glucose PROTEINS Muscles other tissues FAT Triglycerides Adipose tissue They breakdown to amino acids, which are converted to glucose, which is used by the brain LAST CHOICE Enough triglyceride is stored to provide energy for about 2 months GLYCOGEN LIVER Small energy reservoirwith less than a day’s energy needs FIRST CHOICE

  18. How does the body perform all these actions? Using specific hormones. Blood levels of fatty acids Cortisol Epinephrine Growth hormone Blood glucose levels Dominant regulators Opposite actions of those of Insulin Glucagon

  19. INSULIN Polypeptide It is secreted from pancreas

  20. PANCREAS • It is composed of both exocrine and endocrine tissues. • Clusters of cells of the endocrine pancreas • Islets of Langerhans: Clusters of endocrine cells, which secrete hormones and are scattered throughout the pancreas. They make up about 1% to 2% of the total pancreatic mass.

  21. Islets of Langerhans • The islets of Langerhans contain the alpha, beta and other cells. • Beta cells secrete insulin • Alpha cells secrete glucagon

  22. INSULIN AND GLUCOSE It lowers blood levels of glucose It promotes glucose storage Glycogenolysis Breakdown of glycogen into glucose Glycogenesis Conversion of glucose to glycogen in liver and muscles Gluconeogenesis Conversion of amino acids into glucose in the liver Glucose transport into most cells.

  23. Insulin increases glucose uptake in cells It stimulates (after binding to its receptor) the translocation of the glucose transporter 4 (GLUT-4), from intracellular stores to plasma membrane of adipose and muscle cells

  24. Exercise triggers the insertion of GLUT-4 into the plasma membranes of muscle cells even in the absence of insulin Other cells and especially brain cells are freely permeable to glucose: They have other glucose transporters, which are always present in the plasma membrane.

  25. INSULIN AND FATTY ACIDS It lowers blood levels of fatty acids It promotes fatty acids storage Lipolysis Breakdown of triglycerides into fatty acids Synthesis of triglycerides ( from glucose + fatty acids) Fatty acids entry and Glucose entry into adipose tissue cells

  26. INSULIN AND AMINO ACIDS It lowers blood levels of amino acids It promotes amino acids storage (proteins) Protein degradation into amino acids Synthesis of proteins ( from amino acids) Transport of amino acids into muscle cells and cells of other tissues

  27. INSULIN AND MEALS • Insulin exerts anabolic effects by increasing the storage of glucose, fatty acids and amino acids. • This metabolic pattern is characteristic of the absorptive state. • Insulin secretion risesimmediatelyafter a meal. • The opposite takes place in the absence of insulin, with net catabolism to occur. • This pattern is characteristic of the post-absorptive state. Indeed, insulin secretion is reducedseveral hours after food consumption.

  28. Which is the major stimulus of insulin secretion Glucose • Elevated blood glucose levels directly stimulates the β pancreatic cells to synthesize and release insulin. • The opposite happens when the blood glucose falls below normal, such as during fasting

  29. Other factors regulating insulin secretion Excess amino acids and fatty acids increase insulin secretion from beta pancreatic cells. Gastrointestinal hormones secreted by the digestive tract in response to the presence of food stimulate insulin secretion Epinephrine secreted from the adrenal medulla (such as in stressful situations) inhibits insulin secretion.

  30. CONCLUSION

  31. INSULIN DEFICIENCY • Disease: Diabetes mellitus • It affects a large percentage of the population. • It is characterized by elevated glucose levels in blood, or hyperglycemia. • Two types of diabetes mellitus • Both types can be manifested at any age: Type 1 is more prevalent in children, whereas Type 2 in adults.

  32. DIABETES MELLITUS Type 1orinsulin-dependent 10% of diabetics have this type It is characterized by a lack of insulin secretion: Antibodies attack the pancreatic β cells and cause cell death Type 2 or non-insulin dependent 90% of diabetics have this type It is characterized either by a decreased insulin secretion and/or by a decreased sensitivity of tissues to insulin (glucose cannot be taken up by target cells even if sometimes insulin secretion is normal)

  33. HYPERGLYCEMIA The most characteristic feature of type 2 diabetes mellitus is Hyperglycemia (elevated glucose levels in blood). Hyperglycemiais aggravated by the production of glucose (through gluconeogenesis) is further increased due to the elevated levels of amino acids in the blood in the absence of insulin.

  34. MUSCLE WASTING AND WEAKNESS • Insulin promotes the uptake of amino acids by cells and their storage in the form of proteins. • In the absence of insulin amino acids are not taken up by cells and proteins are broken down to amino acids, resulting in muscle wasting and weakness

  35. POLYPHAGIA • Many cells cannot use glucose in the absence of insulin • Cells are starving although blood is full of nutrients • “starvation in the midst of plenty.” • Intense hunger and excessive food intake (polyphagia) • Cells are still being starved: Progressive loss of weight and weakness.

  36. GLUCOSURIA An elevated amount of glucose filtered by the kidney nephrons during urine formation exceeds their capacity for glucose reabsorption. Glucose appears in the urine (Glucosuria)

  37. POLYURIA Glucose in the urine through an osmotic effect draws H2O with it, thus resulting in a large production of urine and frequent urination (Polyuria)

  38. POLYDIPSIA Compensatory mechanism to counteract dehydration is the excessive thirst (Polydipsia)

  39. DEATH • Dehydration can lead to marked reduction in blood volume, peripheral circulatory failure and death.

  40. THE 3 POLY- of DIABETES MELLITUS POLYURIA POLYDIPSIA POLYPHAGIA

  41. KETOSIS Large-scale mobilization of fatty acids from triglyceride stores in the absence of insulin Fatty acids are used as an energy source by the cells Increased use of fatty acids by the liver results in the release of excessive ketone bodies in the blood (ketosis) Ketone bodies include acetoacetic acid, which decreases the pH of blood (acidosis) and acetone, whose exhalation makes the breath to smell like a juicy fruit gum Acidosis depresses the brain and can lead to diabetic coma and death. Diabetic type 2 patients are less prone to develop ketosis than type 1 diabetes patients.

  42. Treatment of diabetes mellitus • Type 1 diabetes mellitus: Injection of exogenous insulin, management of the amounts and types of food consumed, and exercise. • Insulin cannot be swallowed, because it is a peptide that is destroyed by the protein-digesting enzymes in the stomach and small intestine. Type 2 diabetes: Management of the amounts and types of food consumed, exercise, administration of various drugs (that increase insulin release or the sensitivity of tissues to insulin), insulin (if needed) In both types of diabetes, exercise always helps patients because exercise stimulates glucose uptake.

  43. HYPOGLYCEMIA Insulin must be administered very carefully because overdose or extensive exercise in combination with stopping food intake could result in hypoglycemia. Main symptom: depressed brain function, which may progress to unconsciousness and death. In such a case glucose (or a sugar or a candy if the patient is conscious) must be administered.

  44. SUMMARY Metabolism: chemical reactions involving proteins, carbohydrate and fats Digestion: conversion of large nutrients into smaller absorbable nutrients (glucose, fatty acids, amino acids) Conversion of amino acids to glucose (gluconeogenesis) or fatty acids and production of energy Production of glycogen, proteins and fat (triglycerides): anabolism In the absence of dietary glucose, fat, glycogen and proteins are broken down to fatty acids, glucose and amino acids, respectively: catabolism Fatty acids can be used as metabolic fuels by tissues (muscles) thus sparing glucose for brain Absorptive state and post-absorptive (or fasting) state

  45. SUMMARY Metabolism and hormones: growth hormone, epinephrine, glucagon, insulin Insulin and glucagon exert opposite actions Insulin is secreted from the β cells of the islets of langerhans Insulin lowers blood levels of glucose by increasing the glucose uptake into cells and promoting its storage in the form of glycogen Glucose transporters and glucose uptake into cells Insulin lowers blood levels of fatty acids and amino acids and promotes their storage Insulin secretion rises immediately after a meal. The opposite happens many hours after a meal Regulation of insulin secretion

  46. SUMMARY Diabetes mellitus: two types Diabetic mellitus: hyperglycemia, muscle wasting and weakness The 3 poly- of diabetes mellitus Ketosis Treatment of diabetes mellitus Hypoglycemia

  47. NEXT LECTURE Parathyroid Gland and Control of Calcium Metabolism

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