Metabolic Homeostasis Flashcards
What is wasting?
A prolonged fasted state
What type of cytokines are prevalent in pathology that leads to wasting?
Pro-inflammatory cytokines
What axis is activated during times of wasting?
HPA axis
How are growth hormone (and consequently IGF-1) affected by wasting?
They are dysregulated
Describe the “metabolic switch” that occurs after prolonged fasting
Protective mechanism against a prolonged state of fasting - helps your brain get enough nutrients/survive and protects protein breakdown
Ketone body production are now used as a source of energy in the brain. This reduces the demand on the body to use protein for fuel (protein catabolism drops from 300g to 20g a day of break down)
What is the definition of obesity?
BMI >30, waist: hip ratio is greater than 0.95 in men and 0.85 in women
What is the definition of syndrome X (metabolic syndrome)
Visceral obesity (waist >40 inches for men, 35 for women)
Insulin resistance
Dyslipidemia (high TAGs, low HDL)
Hypertension
Metabolic syndrome puts you at risk for developing Type II diabetes
What is the primary hormone produced by adipose tissue?
Leptin
What is the role of the transcription factor Sterol regulatory binding protein 1C (SREBP 1C)?
Promotes TG synthesis and increases glucose “trapping” in cells by upregulating synthesis of glucokinase
What type of receptor is PPARgamma?
nuclear steroid hormone receptor
What is PPARgamma responsible for?
Regulation of TG storage and adipocyte differentiation - makes new adipocytes and makes them bigger
What are thiazolidinediones (TZDs)?
They are PPARgamma agonists used to treat insulin resistance and Type II diabetes mellitus
This works by increasing the storage of fatty acids in adipocytes, thereby decreasing the amount of fatty acids in circulation. As a result cells become more dependent on the oxidation of carbohydrates (glucose) as a source of energy - increase peripheral sensitivity to insulin actions
What is the relationship between the amount of fat someone has and the amount of leptin?
Directly relationship - more fat = more leptin
How does leptin affect appetite?
Leptin stimulates the inhibitors of appetite, and inhibits the stimulators of appetite
Name two stimulators of appetite
Neuropeptide Y
Agouti-related peptide (AGRP)
-Both are from the hypothalamus
Name two inhibitors of appetite
alpha-MSH (cleaved from POMC)
Cocaine-amphetamine regulated transcript (CART)
Discuss the reversibility of insulin-resistances
Insulin-resistance (pre-diabetes) is reversible
Once the diagnosis of type II diabetes has been made, you can’t reverse the resistance, because beta-cells are damaged.
What does insulin resistance refer to?
Insulin resistance –> GLUT4 is not transported to the cell membrane –> glucose is not effectively taken up into the skeletal and adipose tissue –> high blood plasma levels –> hyperinsulinemia –> downregulation of insulin receptors
Over time, pancreas reduces insulin output.
Eventually Type II diabetes mellitus –> type I as beta cells die
How does obesity affect C-peptide and insulin output to the same amount of glucose when compared to a normal person?
An obese person pumps out more insulin and c-peptide in response to the same amount of glucose as a C-peptide
What is HbA1C?
Glycosylated hemoglobin- good indicator of average blood glucose levels over a longer period of time
Anything over 6.5% is considered diabetic
What is polyphagia and why does it occur with diabetes?
Polyphagia = excessive hunger due to inability of cells to utilize glucose “cellular starvation”
You don’t get this with diabetes insipidus, but you do get it with diabetes mellitus
What is polyuria and why is it bad?
Polyuria= excessive glucose in blood- leads to increased plasma osmolality and excessive water and sodium loss
What is polydipsia and why does it occur?
Polydipsia= excessive thirst due to severe dehydration
How do sulfonylurea drugs work to treat Type 2 DM?
They close the K+ ATP-dependent channel in beta cells –> depolarization –> Ca2+ release –> insulin release
