Lecture 10: Metabolic Homeostasis Flashcards
How much glucose does the brain require per day?
180g
How is starvation related to exercise?
initial energy source: 80% fat (release of FFAs, breakdown of liver glycogen/protein)
What does the metabolic switch entail in starvation state?
ketone bodies used as energy source - reduced reliance on glucose
What are the 4 criteria for metabolic syndrome?
1) visceral obesity
2) insulin resistance
3) dyslipidemia
4) hypertension
What is the primary hormone produced by WAT?
Leptin
What are the 2 important transcription factors in WAT?
1) Sterol regulatory binding protein 1C (SREBP-1C)
2) PPARy
What does SREBP-1C do?
1) promotes TG synthesis
2) increases glucokinase trapping glucose inside cells
(activated by lipids and insulin)
What does PPARy do and what is its receptor?
regulates/promotes TG storage and adipocyte differentiation (lipids are the ligand)
INCREASES # of adipocytes
How has PPARy been drugable to treat diabetes type 2?
agonists treat insulin resistance (promote TG storage but also makes more fat)
side effect is weight gain
What is the class of PPARy agonists?
TZDs (thiazolidinediones)
as leptin increases, what happens to fat?
increases (direct relationship)
What are 2 hypothalamic hormone stimulators of appetite?
1) Neuropeptide Y
2) Agouti-related peptide
What are 2 inhibitors of appetite?
1) aMSH (cleaved from POMC)
2) CART
How does leptin affect appetite?
inhibits it!
Why do obese people have high levels of leptin?
leptin resistant
What leads to DM?
reduced production of insulin by pancreas (beta cell depletion/exhaustion)
What happens to insulin receptors in hyperinsulinemia?
DOWNREGULATED
What is the ultimate diagnosis of T2DM?
elevated HbA1c (>48mMol/l)
What is HbA1c
a measure of glycosylated RBCs (too much glucose in the plasma, eventually starts to stick on RBCs)
What is the fasting blood glucose in pre-diabetic patients?
100-125mg/dl
What is the oral glucose tolerance test?
8 hour fast, measure glucose before and 2h after consumption of 75g glucose
What does C-peptide tell you?
indication of how well the pancreas is working
What are 3 symptoms of T2DM?
1) Polyphagia (cellular starvation)
2) Polyuria (excess glucose in blood leads to increased plasma osmolarity pulling H2O)
3) Polydipsia (severe dehydration)
How do Sulfonylurea drugs help T2DM patients?
stimulate insulin release (close ATP dependent K+ channels)
What are examples of sulfonylureas?
glipizide
glyburide
What does metformin do?
inhibits hepatic gluconeogenesis
increases insulin receptor activity
What do alpha glucosidase inhibitors like precose or glyset do?
delay intestinal absorption of carbs
What are some leading theories behind beta cell dsyfunction?
1) islet amyloid buildup
2) ER stress
3) lipotoxicity
Ketoacidosis characterizes which type of diabetes?
1 (in the absence of insulin therapy)
How does ketoacidosis occur in T1DM?
increase FFA release (hepatic precursor for ketone acids) —-> metabolism of ketone bodies for energy —-> increased blood acidity —-> diabetic coma/severe dehydration
What is the main difference between absolute and relative insulin deficiency?
Absolute: lipolysis (increases ketogenesis)
How is mental acuity related to blood sugar?
increase blood sugar, increase blood osmolarity (dehydrates)
alert (320mOsm) drowsy (330) stupor (340) coma (360)
How are GH and insulin related?
AA from protein stimulates GH which stimulates IGF-1
IGF-1 simulates glucose uptake in muscle, proliferation of visceral organ tissues, inhibits proteolysis
GH opposes insulin lipogenesis
is GH high or low in times of starvation?
HIGH
(increased AA from proteolysis stimulates it)
but no IGF-1 (no insulin) so no negative feedback on GH
List the physiological hallmarks of starvation
1) No insulin, low glucose
2) catecholamines stimulate glucagon
3) GH increases (increase AA due to proteolysis)
4) no negative feedback on GH (no IGF-1)
5) Cortisol (stress) increases
What is the most highly associated genetic polymorphism in T2DM?
TCF72 (part of Wnt signaling) participates in islet cell development
When does islet neogenesis occur?
embryonic development (beta cell replication continues during childhood but is stable in adults)
