Download Lecture 22

Control of Energy
The Original Biofuels
Importance of Glucose Regulation
• Too little – Brain problems
• Too much
– Osmotic water loss (cellular and systemic)
– Damages blood vessels
Role of the Pancreas
1. Digestion – secretes digestive enzymes
2. Metabolism
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Regulation
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Carbohydrates
Lipids
Proteins
Produces primary messengers (hormones)
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Insulin
Glucagon
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Insulin discovered by
Frederick Banting and Charles
Best in 1921.
Leonard Thompson (age 14,
65lbs) first patient successfully
treated.
• 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
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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
Most Cells
Insulin
Control
 Protein synthesis
Muscle
 Glucose uptake
 Glycogen synthesis
Gastrointestinal
hormones
Adipose
Amino
acids
Pancreas
 amino
acids
 Insulin
 triglycerides
 Glucose uptake
 Glycerol production
 Triglyceride breakdown
 Triglyceride synthesis
Beta cells
Liver
Blood
glucose
 Glucose uptake
 Glycogen synthesis
 Fatty acid synthesis
 Glucose synthesis
Brain
No effect
Feedback
 glucose
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
1)
2)
β – adrenergic
stimulation
glucagon
Glucagon
Control
 Triglyceride breakdown
 Triglyceride storage
Exercise
Amino acids
Adipose
 Fatty acids
Pancreas
Alpha cells
Epinephrine
(stress)
Liver
 Glycogen breakdown
 Glucose synthesis
 Glucose release
Brain
No effect
Feedback
 Blood glucose
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
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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)
Microencapsulation Approach