Physiology 3120 Lecture Notes - Insulin Resistance, Polyphagia, Angiopathy

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26 Nov 2011
Human Physiology
Monday, March 1, 2010
“Endocrine V”
Diabetes Mellitus
Diabetes – Greek (large volume of urine); mellitus – Latin (a sweet taste)
Once tested for by observing whether ants would swarm around a person’s urine; therefore
referred to as “sweet urine disease” (Madhumeha)
Characterized by hyperglycemia (too much glucose in bloodstream); polyphagia (eating frequently);
polyuria; glycosuria (glucose in the urine); water and electrolyte loss
In severe cases, get ketosis (build-up of ketones in bloodstream), acidosis, coma and death
Long-term complications: retinopathy (damage to retina or lens; get expansion and contraction);
nephropathy; angiopathy
Insulin stimulates. . .
Glucose uptake
Diabetes mellitus
Type I
Insulin-dependent; failure to secrete sufficient insulin to regulate glucose utilization
Autoimmune destruction of pancreatic B-islet cells; B-islet cells produces proteins after
an “insult” that promote immune reaction; the cascade is fairly rapid once it’s initiated
Early onset
Only ~10% of diabetics
Inability to import glucose; alternate energy source needed
oIncreased gluconeogenesis (mostly in liver)
oMuscle broken down to AA, which is converted into glucose in liver;
causes (I) muscle wasting and (II) weight loss
Fat (more predominant)
oIncreased lipolysis
oMobilization of triglycerides and free fatty acids (FFAs) for energy;
clipped into acetyl-CoA, which can then enter the citric acid cycle
oBy-products are ketones (results in ketosis)
Fate of high serum glucose
Increased glucose filtration = water excretion = dehydration
Glucose converted to sorbitol (via the “polyol pathway”) which damages the lens,
nerves, and capillaries
Increased glycosylation of proteins (via the “glyoxal pathway”; especially
haemoglobin); end-products are diagnostic (levels of glycosylated haemoglobin
resides in serum for a long time) and damaging
Type II
Insulin resistant/impaired insulin secretion; overall, a decreased cellular response to
“Lifestyle” – overweight and sedentary
Onset in mid-life (now seeing more and more cases in juveniles)
~90% of diabetics
Complex interplay of factors contribute to insulin resistance
oMuscle is major user of glucose, so regular exercise maintains the tuning
of the insulin release system
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