Importance of Glucose Regulation Too little – Brain problems

Importance of Glucose Regulation

• Too little – Brain problems

• Too much

• Osmotic water loss (cellular and systemic)
• Damages blood vessels

Role of the Pancreas

• Digestion – secretes digestive enzymes

• Metabolism

• Regulation
• Carbohydrates
• Lipids
• Proteins
• Produces primary messengers (hormones)
• Insulin
• Glucagon

Insulin discovered by Frederick Banting and Charles Best in 1921.

• Insulin discovered by Frederick Banting and Charles Best in 1921.

• Leonard Thompson (age 14, 65lbs) first patient successfully treated.

51 amino acids

• 51 amino acids

• 2 chains linked by disulfide bonds

• 5800 Dalton molecular weight

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)

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

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)

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

Insulin Control

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

Glucagon Control

Importance of Glucose Regulation

• Too little – Brain problems

• Too much

• Osmotic water loss (cellular and systemic)
• Damages blood vessels

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

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

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)