Physiology 3120 Lecture Notes - Lecture 55: Diabetes Mellitus Type 1, Insulin Receptor, Adipocyte
15 May 2018
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Lecture 55 – Diabetes and Insulin Resistance
Diabetes mellitus
- Diabetes—Greek - large volume of urine
- Mellitus—Latin - a sweet taste
- Diabetes: large volume of sweet tasting urine = urine with high amounts of glucose
- Insulin acts to bring glucose from circulation into the tissue to lower blood glucose after a
meal → store it away in higher energy forms for later during fasting
- The ancient Indians tested for diabetes by observing whether ants were attracted to a
person's urine, and called the ailment "sweet urine disease" (Madhumeha)
- The Korean, Chinese, and Japanese words for diabetes also mean "sweet urine disease"
- Does not impair lifespan but does influence the quality of life
- Diabetic patients have issues with eyesight, kidney failure, lack of circulation (los of limbs)
- Characterized by:
o Hyperglycemia: high blood glucose
o Polyphagia (eating with weight loss)
o Polyuria (high urine volume)
o Glycosuria (glucose in urine)
o Water and electrolyte loss (dehydration)
- In severe cases if untreated:
o Ketosis (high ketones in circulation = poisonous to cells)
o Acidosis
o Coma and death in long term
- Long-term complications (secondary conditions):
o Retinopathy (impaired vision)
o Nephropathy (impaired kidney function)
o Angiopathy (blood clots) ultimately leading to limb amputations
o Increased susceptibility to infection
o (even if you control blood glucose, long term complications can still occur)
- Type I diabetes mellitus:
o Insulin-dependent
o Autoimmune destruction of pancreatic cells
o No beta cells to support needs to body to lower blood glucose
o Lack of insulin production (no insulin to lower circulating glucose)
o Early onset juvenile diabetes – children and adolescents
o ~10% of diabetics
- Type II diabetes mellitus:
o Insulin resistant/impaired insulin secretion
o Hormone is still being made but not responding when it binds to its receptor
o Insulin receptor is impaired = impaired response
o Lifestyle issues - overweight, sedentary (lack of activity)
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o Onset in mid-life (adulthood – 30-40 years of age)
o 90% of diabetics
o With childhood obesity, type II is occurring in younger population (20 years old)
Type I diabetes
- A failure to secrete sufficient insulin to regulate glucose utilization
- Autoimmune disease
o Body thinks that the beta cell is foreign and T cells from thymus destroy beta cells
- Non obese diabetic mouse:
o Over time, the mouse develops type I diabetes
o As the disease progresses, T cells infiltrate and attack beta cells and destroy them
o No insulin-positive beta cells remain in the Islets of Langerhans
o = complete loss of insulin production
- ~ 10% of all diabetes; early onset
- Insulin-dependent
- Early symptoms: high glucose, high urine output, dehydration, low energy
What happens without insulin?
- High glucose circulating in the body
- Inability to transport glucose into cells of organs (e.g. adipose and muscle)
o Require insulin to bring glucose into the organs (via activation of GLUT4)
o If cannot bring glucose into muscle or adipose cells, both cell types require an
alternate way to generate energy
o = alternate energy source needed but in long term this is detrimental
- Breakdown their own protein or fat inside the cells to generate ATP
Other sources of energy – protein
- Muscles broken down to AA
- Amino acids that are liberated from the break down of muscle and protein can be used to
make glucose in the muscle and AA can be used in the liver to generate more glucose and
ATP for the livers needs
- Muscle takes a hit to help the liver
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- AA converted to glucose in liver (used by liver, brain)
- OVERALL: decrease in muscle, decrease in protein, increase in AA
- Without insulin, this results in:
o Muscle wasting (degraded, increase AA)
o Weight loss (lose muscle weight)
Other sources of energy – fat
- Adipose cells breaks down fat through lipolysis
- Lyse fat into triglycerides and free fatty acids which are the source of ATP
- Lose fat inside the adipose cell (cell is storage center for fat)
- Mobilization of TG and FFA from stores
- Fat is broken down into free fatty acids and they are used for the TCA cycle (not glucose) to
generate ATP
- Free fatty acid oxidation is the alternate form to generate ATP in adipose cells
- By-products include ketones
o High amounts of ketones are generated from free fatty acid oxidation/lipolysis
o High ketones are a marker of diabetes
o High amounts can lead to ketoacidosis can lead to death (poisonous to the cell and
organism)
- Lipolysis is good in the short term for generation of ATP but not good for the organism in
the long term
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