L77: Metabolic Homeostasis Flashcards
WHO definition of obesity
BMI greater than 30
Waist-hip ratio greater than 0.95 (men) and 0.85 (women)
Metabolic syndrome (Syndrome X)
visceral obesity, insulin resistance, dyslipidemia, hypertension
visceral obesity, insulin resistance, dyslipidemia, hypertension
Metabolic syndrome (Syndrome X)
PPARγ
Peroxisome proliferator-activated receptor gamma: Nuclear steroid hormone receptor. Regulates TG storage and adipocyte differentiation - makes more fat cells
Thiazolidinediones (TZD)
PPARγ agonists used to treat insulin resistance and
Type II diabetes “Rosiglitazone = Avandia”)
Obese people have high levels of
leptin
Leptin is produced by
adipocytes
There is a direct relationship between leptin and
total fat
Relationship between total fat and plasma
leptin concentrations.
Higher body fat
correlates with increased plasma levels of leptin. Leptin inhibits appetite and food intake during the normal fed state. Obese people have
very high levels of leptin, but are potentially insensitive to leptin effects.
Neuropeptide Y
hypothalamic stimulator of appetite
Agouti-Related Peptide (AGRP)
hypothalamic stimulator of appetite
αMSH
hypothalamic suppressor of appetite
Cocaine-amphetamine regulated transcript (CART)
hypothalamic suppressor of appetite
Leptin inhibits which hypothalamic regulators of appetite?
Neuropeptide Y and AGRP
Leptin stimulates which hypothalamic regulators of appetite?
αMSH
CART
Insulin does not efficiently transport glucose into cells. Glucose levels are high
Insulin resistance
What promotes conversion from T1DM to T2DM?
Beta cell depletion or “exhaustion” will cause conversion from Type II to Type I diabetes
Measures average blood glucose
concentrations over a longer period
of time.
Elevated HbA1C: ≥48mMol/l (6.5%)
Normal vs. pre-diabetic fasting glucose
Fasting blood glucose: 100-125 mg/dl (pre-diabetes), 126+ T2DM
Leptin deficient mice are
morbidly obese
HbA1C is effective because the lifespan of RBC is
120 days
pre-diabetic fasting glucose?
100-124mg/dl
Fasting glucose for T2DM?
126+ mg/dl
What are the “3P” symptoms of T2DM?
Polyphagia
Polyuria
Polydipsia
Polyphagia
excessive hunger due to inability of cells to utilize glucose “cellular starvation”
Polyuria
excess glucose in blood leads to increased plasma osmolarity, excessive water and Na+ loss
Polydipsia
excessive thirst due to severe dehydration
What does Procose or Glyset do? Hint: alpha-glucosidase inhibitors.
Delays intestinal absorption of carbs
What does metformin do?
Inhibits hepatic gluconeogenesis, and enhances insulin receptor activity
What does “Glipizide” do? Hint: sulfonylurea drug
Closes K+ channel on B-cell, promoting depolarization and Ca+ influx, thus insulin secretion
What kind of diabetes exhibits KETOACIDOSIS without insulin therapy?
Type 1 DM
Side effect of TZD
weight gain
Direct relationship between plasma leptin and
total fat
Indirect relationship between ghrelin and
obesity
Name 4 counter regulatory hormones to insulin
GH
Cortisol
Catecholamines
Glucagon
Declined mental status in DM results from
dehydration accompanying hyper osmotic hyperglycemic state (both T2DM and T1DM)
TCF72
most highly associated genetic polymorphism in T2DM. This is a Wnt signaling pathway player, co-activatory of beta-catetenin. Downstream targets regulate B-cell proliferation.
Which DM is reversible?
T2DM
PDX-1
important for both islet neogenesis and beta-cell proliferation
Bonus: what is Exenatide?
incretin mimetic
