Control of Energy The Original Biofuels

1. Control of Energy The Original Biofuels

2. Importance of Glucose Regulation • Too little – Brain problems • Too much • Osmotic water loss (cellular and systemic) • Damages blood vessels

3. Role of the Pancreas • Digestion – secretes digestive enzymes • Metabolism • Regulation • Carbohydrates • Lipids • Proteins • Produces primary messengers (hormones) • Insulin • Glucagon

4. Insulin discovered byFrederick Banting and Charles Best in 1921. • Leonard Thompson (age 14, 65lbs) first patient successfully treated.

5. 51 amino acids • 2 chains linked by disulfide bonds • 5800 Dalton molecular weight

6. Effects of Insulin • Nearly all cells (80%) increase glucose uptake (seconds) • Active transport • Primarily affects liver and muscle • Brain tissue is excepted • Alters phosphorylation of many key intracellular metabolic enzymes (minutes) • Alters protein synthesis and gene transcription (hours)

17. Insulin Affects Tissues Differently • Muscle • Uptake of glucose and immediate use (exercise) or storage as glycogen (Exercising muscles can take up glucose without insulin) • Liver • Uptake of glucose and storage as glycogen • Inhibits glycogen phosphorylase • Activates glycogen synthase • Inhibits glucose synthesis • Promotes excess glucose conversion to fatty acids • Adipose Tissue • Promotes glucose uptake and conversion to glycerol for fat production

21. Insulin and Fat Metabolism • Liver cells store glycogen only up to 5-6% • Remaining glucose metabolized to fat • Triglycerides are synthesized and release into blood • Adipose cells store fat • Inhibits breakdown of triglycerides • Stimulates uptake and use of glucose to form glycerol • Stimulates fatty acid uptake and conversion to triglycerides • Lack of insulin • Free fatty acids build up in blood • Liver metabolizes to produce phospholipids and cholesterol • Can lead to excess acetoacetic acid production and buildup of acetone (acidosis, which can lead to blindness and coma)

22. Insulin and Protein Metabolism • Promotes • Transport of amino acids • Protein synthesis • Gene transcription • Inhibits protein degradation • Prevents glucose synthesis in liver • Preserves amino acids • Lack of insulin causes elimination of protein stores

23. Most Cells  Protein synthesis  amino acids Insulin Control Muscle  Glucose uptake  Glycogen synthesis Gastrointestinal hormones • Adipose • Glucose uptake • Glycerol production • Triglyceride breakdown •  Triglyceride synthesis  triglycerides Amino acids Pancreas Beta cells  Insulin • Liver •  Glucose uptake • Glycogen synthesis • Fatty acid synthesis • Glucose synthesis Bloodglucose  glucose Brain No effect Feedback

24. Effects of Glucagon • Prevents hypoglycemia • Powerful system to degrade glycogen • Increases glucose synthesis from amino acids • Increases with exercise independent of blood glucose • Exerts effects through cAMP second messenger system

27. β – adrenergicstimulation • glucagon

28. Glucagon Control • Adipose • Triglyceride breakdown • Triglyceride storage  Fatty acids Exercise Amino acids Pancreas Alpha cells • Liver •  Glycogen breakdown • Glucose synthesis •  Glucose release  Blood glucose Epinephrine (stress) Brain No effect Feedback

29. Importance of Glucose Regulation • Too little – Brain problems • Too much • Osmotic water loss (cellular and systemic) • Damages blood vessels

32. Diabetes Mellitus • Type I • Insulin dependent • Juvenile onset • Causes • Increased blood glucose (300-1,200 mg/100ml) • Increased blood fatty acids and cholesterol • Protein depletion • Treated with insulin injections • Increases risk of heart disease and stroke • Can cause acidosis and coma

33. Diabetes Mellitus • Type II • Non-insulin dependent • Results from insulin insensitivity • Elevated insulin levels • Associated with obesity • Can lead to insulin dependent form • Treated with weight loss, diet restriction, exercise and drugs

37. Diabetes • 143 million suffer worldwide (W.H.O.) • Expected to double by 2025 • Costs $143B annually • Treatment with insulin is not optimal • Does not mimic normal control system • Associated with serious health risks • Direct transplantation has not proven feasible • Immunosuppression causes problems • Use of semi permeable encapsulation may be possible • Must optimize for nutrient exchange but immune isolation • Biocompatible and structurally sound • Prevent allergic responses • Must provide glucose control • Other options may be effective (e.g., gene therapy)

38. Microencapsulation Approach