Transcript Regulation of insulin levels

Regulation of insulin levels
• Starter: what do each of the following
cells produce and are they part of the
endocrine or exocrine system;
– α cells
– β cells
– Pancreatic cells surrounding tubules
Objectives
• Explain the role of the pancreas in blood
glucose regulation
• Explain how insulin secretion is
controlled by the β cells in the islets of
Langerhans
• Compare and contrast the causes of
type 1 and type 2 diabetes
• Discuss the use of insulin produced by
genetically modified bacteria
Importance of Glucose Regulation
• Too little – Brain problems
• Too much
– Osmotic water loss (cellular and systemic)
– Damages blood vessels
We eat food containing carbohydrates
The carbohydrates
are fully digested
to glucose which
is absorbed
The carbohydrates are fully digested
to glucose which is absorbed
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.
The pancreas detects the change
in blood glucose concentration and
releases the appropriate hormone
• 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)
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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
Insulin
Control
Gastrointestinal
hormones
Most Cells
 Protein synthesis
Muscle
 Glucose uptake
 Glycogen synthesis
Adipose
Amino
acids
Pancreas  Insulin
 amino
acids
 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
Glucagon
Control
 Triglyceride breakdown
 Triglyceride storage
Exercise
Amino acids
Adipose
Pancreas
Alpha cells
Epinephrine
(stress)
 Fatty acids
Liver
 Glycogen breakdown
 Glucose synthesis
 Glucose release
Brain
No effect
Feedback
 Blood glucose
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)
Diabetes mellitus
• Blood glucose level fluctuate due to
eating and exercise
• Diabetes mellitus is a disease in which
the body can no longer control the blood
glucose levels
• This can lead to;
– hyperglycaemia – blood sugar level too high
– hypoglycaemia – blood sugar level too low
Types of diabets
• There are two main types of diabetes;
– Type 1 – early onset
– Type 2 – late onset
http://www.5min.com/Video/What-is-Diabetes-18630948
Type 1 diabetes
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Usually starts in childhood
Aka insulin-dependant diabetes
The body no longer makes any insulin
Body cannot store excess glucose and
glycogen
• It is thought that this is the result of
an autoimmune response which the body
destroys its own β cells
Type 2
• Usually starts later in life due to
obesity/aging
• Aka non-insulin dependant
• Body does not respond properly to
insulin/ insulin is not produced enough
• Certain factors bring on earlier onset;
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Obesity
Diet high in sugar
Being of Asian/ afro Caribbean
Family history
Insulin therapy
• Where does the insulin come from that
is injected into people with type 1
diabetes?
http://www.youtube.com/watch?v=m3925Pw-VwU