Insulin%20Dependent%20Diabetes%20Mellitus

1
Lecture 25

• Insulin Dependent Diabetes Mellitus
• Type 1 Diabetes
• Juvenile Onset Diabetes

2
500 BC

• Frequent urination
• Rapid loss of weight
• Unquenchable thirst
• Sweet breath
• Death within a few weeks
• Diabetes
• Urine contains sugar
• Mellitus

3
Hypoinsulinemia

• Think about what insulin does
• Not just anabolic, also anti-catabolic
• Prevents
• Glycogenolysis
• Proteolysis
• Lipolysis
• Stimulates
• Glucose uptake and disposal

4
Lack of Insulin

• Poor glucose uptake into cells
• But not zero, and only muscle/WAT affected
• Will elicit a bit of hyperglycemia
• Poor lipogenesis glycogenesis
• Of little consequence
• Massive, uncontrolled lipolysis
• Huge release of fatty acids into the bloodstream
• And glycerol
• High rates of fatty acid oxidation
• Inhibits glucose oxidation, glucose ? lactate
• High rates of ketone body production
• Inhibts glucose metabolism in the brain
• Uncontrolled proteolysis
• Breakdown of tissues
• Release of amino acids into bloodstream

5
Lipolysis Proteolysis

• Weight loss
• Dangerous loss of essential protein
• Increasing hyperglycemia
• High rates of gluconeogenesis
• Glycerol, amino acids lactate as substrates
• Fatty acid oxidation stimulating pyruvate
  carboxylase
• Low insulin, increased cAMP ? increased F16BPase
• Low rates of glucose disposal
• Blood acidity rises
• Fatty acids, lactate, ketone bodies all acidic
• Ketoacidosis
• Ketone bodies decarboxylate
• Acetone lost on breath

6
Hyperglycemia

• Glycosylation increases
• But long term
• Loss of glucose in urine
• Glucose reabsorbtion by kidneys reduced above
  glucoseblood 10 mM
• Osmolality of blood changes
• Draws water out of the tissues
• Massive thrist
• Increased water intake
• Increased urination
• Loss of electrolytes

7
Treatment

• Insulin
• Discovered first used in 1922
• Tight control to avoid complications
• Blood glucose monitoring
• Tailored insulin injections
• Long and short acting forms
• Risk of hypoglycemia
• Hypoglycemia unawareness