Lecture 10 Flashcards
(49 cards)
Wasting-prolonged pasting state leads to proinflammatory cytokines, what 2 things happen next?
- activation of HPA axis
- tries to mediate inflammation but then becomes dysregulated and becomes overactive - dysregulation of GH and IGF-1
- (main hormones controlling growth)
The brain needs 180g/day of glucose how does it get this glucose without food?
- initial source: liver gluconeogenesis
As Starvation continues - break down protein and fat
-protein is initially broken down at a very high rate of 300 g/day
What happens after a couple days of starvation?
- the liver glycogen will all be depleted
- the increased amino acids from the breakdown of protein will activate GH
- GH hormone conserves lean body mass-reuptake of aa back into muscles
- metabolic switch
What is the metabolic switch?
switch to ketone bodies as source of energy for brain
- reduced reliance on glucose as fuel source
- protein breakdown continues at (20g/day)
How does glucose enter the brain?
GLUT 3 insulin independent manner
What is obesity defined as?
BMI greater than 30 (at least 20% of the population)
Waist-Hip ratio greater than .95 (men) or .85 (women) indicates significant risk for cardiovascular disease and diabetes
What is metabolic syndrome “syndrome x” defined by?
visceral obesity= waist >40in men, 35 in in women
insulin resistance-fasting glucose is greater than 100mg/dl
dyslipidemia-TG greater than 150 mg/dl, HDL less than 40mg/dl
Hypertension-BP> 135/80
-could indicate you are prediabetic
What does an adipocyte store? What is the primary hormone produce?
TG storage cell
hormone= Leptin
What does Sterol regulatory binding protein 1C (SREBP-1C) do in adipocytes?
Promotes TG synthesis
Activated by lipids and insulin
Increases glucose “trapping” glucose inside cells. And then turns them into triglycerides
What doe PPARgamma do in adipocytes?
Nuclear steroid hormone receptor
Regulates TG storage and adipocyte differentiation
- Ligand for this receptor is lipids
- Acts as TF–> promotes TG storage and increases the number of adipocytes
What is an agonist of PPAR gamma? What does it do?
Thiazolidinediones (TZD)- PPAR gamma agonist used to treat insulin resistance and Type 2 diabetes mellitus
- induces adipocyte differentiation-more fat cells–>more cells that can take up the glucose
- increased fat storage
-side effect is weight gain
WHat is leptin produced by? What is the relationship between leptin and total fat?
Produced by adipocytes
-the more fat you have the more leptin you will release
What are stimulators of appetite?
Neuropeptide Y
Agouti-regulated peptide (AGRP)
*leptin inhibits these cause decreased food intake
What are inhibitors are inhibitors of appetite?
alpha MSH-cleaved from POMC
Cocaine-amphetamine regulated transcript (CART)
*leptin stimulates these decreasing food intake
What happens to leptin deficient mice? What is the paradox of this with humans?
appetite is uncontrolled=mouse gets very fat
Paradox: obese humans have leptin–>possibly in obesity there is an induced leptin resistance
What is insulin resistance? What happens to glucose levels? What does this lead to?
- insulin does not efficiently transport glucose into cells(insulin dependent transporters in muscles and adipose–make up bulk of body mass)
- plasma glucose levels are high-hyperinsulinemia–>down regulates insulin receptors
- gradual process can take decades to develop into diabetes
- over time pancreas reduces insulin output leading to diabetes mellitus
What causes the conversion from type 2 to type 1?
beta cell depletion or exhaustion
What eventually leads to insulin resistance in obese patients?
overcompensation
-low plasma blood glucose, high plasma insulin, and high plasma c-peptide
What does HbA1C measure? What is the amount need to diagnose Diabetes mellitus type 2?
Elevated HbA1C >48 mMol/L(6.5%)
-measures average blood glucose concentrations over a longer period of time
(average RBC lifespan=120 days, glucose increases the number of glycosylated RBCs)
What is the fasting blood glucose number for prediabetes? T2DM?
Pre diabetes = 100-125
T2DM=126+
How does an oral glucose tolerance test work?
8 hour fast
-glucose measured before and 2h post consumption of glucose
140-199= pre diabetes 200+= T2DM
What is T2DM characterized by? What are the symptoms?
-impaired beta cell function and insulin resistance
Symptoms
Polyphagia-excessive hunger due to inability of cells to utilize glucose “cellular starvation”
Polyuria-excess glucose in blood lead to increased plasma osmolarity, excessive water and sodium loss (pulls water out of cells)
Polydipsia-excessive thirst due severe dehydration
(impaired filtration in the kidney, glucose in urine–>pulls water in and sodium follows)
What is the treatment goal for T2DM?
What do sulfonylureas, biguanides, and alpha glucosidase inhibitors do?
tight glycemic control
- Sulfonylureas-“Glyburide”, “glyipizide”
- close ATP dependent K+ channels in beta cells causing insulin release - Biguanide- “metformin”
- inhibit hepatic gluconeogenesis
- increase insulin receptor activity making more cells more sensitive to insulin, increased glucose uptake
- first line of treatment - alpha-glucosidase inhibitors: “precose” “glyset”
- delays intestinal absorption of carbohydrates
- gives pancreas time to catch up - farxiga
- makes it so kidney cant take up as much glucose–>secretes it in the urine–>yeast infection and bladder infection
What are some proposed mechanisms of beta cell dysfunction?
- islet amyloid buildup
- endoplasmic reticulum stress
- lipotoxicity
- oxidative stress
- glucose toxicity
- beta cell differentiation-reduced expression of key beta cell genes
- incretin hormone dysregulation(made in intestine, respond to high carb load)
- islet inflammation
