Diabeetus Flashcards
Functions of insulin
Stimulates taking GLUT4 transporters from vesicles and places them on the cell membrane Antagonizes glucagon release Signals that we are well fed and it's time to repair things Acts as a growth factor Stimulates protein synthesis Increases amino acid uptake Trigger glycolysis (to make ATP) Triggers glycogen synthesis Stimulates fat storage (TG synthesis) Acts as an appetite suppressant
Insulin receptor
The insulin receptor is a dimer. When insulin binds, the dimers come together, creating the active insulin receptor. It triggers a bunch of intracellular stuff that results in GLUT 4 receptors being placed on the cell membrane, as well as increase transport of amino acid, potassium, magnesium, and phosphate.
How does giving insulin and glucose lower K+ levels in the cell?
Causes a bunch of glucose to enter the cell, make a shit-ton of ATP, makes the Na/K/ATP pump run faster and bring more K+ into the cell.
These cells do not rely on insulin for glucose uptake
Neurons and cardiomyocytes
(they have insulin receptors, but probably serve more as a growth factor effect than serve to bring glucose into the cell)
What happens to glucose taken up by muscle cells?
Converted to glycogen or fat. Muscles can store glucose in either of these forms within the cell.
Can we convert fat into glucose?
NO. However, we can use the glycerol on a TG to make glucose.
Why are diabetics more prone to DKA than non-diabetics?
Because they make ketones at a VERY high rate
This organ tries to maintain BG levels between meals
Liver
These two cell types can ONLY use glucose
Brain and RBCs
However, the heart and skeletal muscle are able to burn fat.
Alpha cells make ____ and beta cells make ___. Delta cells make ____.
Alpha = glucagon Beta = insulin Delta = somatostatin
Insulin secretion is stimulated by _____.
Glucagon secretion is inhibited by ____.
Glucose.
Insulin.
How is insulin released from beta cells?
GLUT 2 receptors on beta cells (always there) bring in glucose. Rate of uptake depends on glucose concentration. Once inside, a shit ton of ATP is made. This ATP acts as a signal to close the ATP-sensitice K+ channel. Because it is now closed, K+ builds up and results in depolarization. This depolarization activates voltage-sensitive Ca channels. Ca++ rushes in and causes release of insulin-filled vesicles.
Thus overall, increased glucose = increased ATP = increased insulin release.
Low glucose = low ATP = low insulin release.
What are ketones a sign of?
They are a sign that we’re burning fat.
What is more common, type 1 or 2 DM?
Type 2 (90% of cases) Type 1 (10% of cases)
What is MODY?
Maturity onset diabetes of youth
Basically, your B cells are there, but defective in either making insulin or releasing it. This form can be treated with oral hypoglycemics.
In the pregnant woman, is BG controlled by the fetus or the mother?
The fetus, because it is essential that the fetus receives enough glucose for development.
These endocrine disorders can cause diabetes
Cushing’s, acromegaly, or pheochromocytoma
because cortisol, GH, and NE all try to increase BG levels
What is beta cell exhaustion?
The way that beta cells are killed in Type II diabetes
basically, so much intracellular glucose, that these high levels start killing the cells -> glycotoxicity
Type 1 DM is due to a type __ hypersensitivity reaction
IV
Do we see DKA in type 2 DM?
Not usually, because high insulin levels exist, which keeps glucagon low. Later in cell if B cells are destroyed, high glucagon can result in DKA.
Diagnosis of DM
Fasting BG > 126
OR
BG > 200 after 2 hours during an OGTT
Pre-diabetes is also called
Impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). These are two different things.
IFG is BG of 100-125 after overnight fast.
IGT is BG of 140-199 after 2 hours during an OGTT.
___% of Americans have pre-diabetes
40%
Most of these people will go on to develop full-on DM. But! There is a lot you can do to prevent developing DM!
Hypoglycemia dx and s/s
BG < 70
Mild:
Hunger, shakiness, paleness, sweating, anxiety, blurry vision
SEVERE:
Extreme tiredness, confusion, combativeness, dazed appearance, seizures, unconsciousness, coma, DEATH
Formula for filtered load
Concentration x GFR
Tmax reabsorption for glucose
300mg/min
Can the brain burn ketones?
Yes, but it takes a few days for it to switch gears and be able to use this source
Basic problem with DKA
Often happens due to insufficient exogenous insulin, or is the first sign of DM. Also, anything that raises stress can increase risk of DKA.
Not enough insulin causes excessive glucagon. This causes increased glucose release from the liver and life-threatening levels of hyperglycemia (can cause brain damage). High glucagon also causes ffas to be converted to ketones for energy, causing ANION GAP acidosis. The high glucose also causes osmotic diuresis and hypovolemia and electrolyte disturbances. They hay also have N/V, contributing to the dehydration and electrolyte disturbances. There will be glucose and ketones in the urine!
How does HONKS occur
Similar to DKA, but in Type II patients. Some sort of stressor increases BG levels. This causes osmotic diuresis and extremely high BG levels and osmolarity. Insulin is present in this syndrome however, so ketones are not produced, and person does not become acidotic.
What normally happens to glycosylated proteins in our body?
They are eaten by macrophages. In diabetes, macrophages can’t keep up, and levels of glycosylated proteins increase.
Chronic complications of DM
Retinopathy Cataracts Glaucome HTN CVA CAD/MI PVD Gangrene Peripheral and autonomic neuropathies Gastroparesis
Unchecked BG causes production of
Advanced glycosylation end-products (AGEs)
Production sequence of AGEs
Glucose + protein => Schiff Base => Amadori Product => AGE
HbA1C looks for Amadori Products
AGEs are what macrophages clear
Progression to AGE is irreversible
How does DM cause kidney failure?
A fuck-ton of macrophages hang around the glomerulus, eating up AGEs. Macrophages being active here damage the glomeruli
HgA1C looks for these products
Amadori products
Damaging chemical properties of AGEs
They cross-link polypeptides of same protein (collagen)
They trap non-glycosylated proteins (LDL, Ig, complement)
They resist proteolytic digestion
Induce lipid oxidation
Inactivate NO
Bind nucleic acids
AGEs bind to these receptors and induce
AGE receptors (RAGE) on monocytes and mesenchymal cells, causing:
1) Monocyte emigration
2) Increased vascular permeability
3) Cytokine and growth factor secretion
4) Procoagulant activity
5) Enhanced cellular proliferation
6) Enhances ECM production
Normal HbA1C is ____ and we want diabetics to be less than ____
4-5
7
Should the goal of DM II be lifestyle modification or HbA1C reduction?
Life-style modification!!!
Two phases of diabetic retinopathy
Background retinopathy- early phase, retinal arteries are weak and form small, dot-like microhemorrhages, causing patchy vision loss
Proliferative retinopathy- the retina is now become ischemic. New and fragile vessels proliferate to compensate, but these hemorrhage easily.
How to prevent type II DM
Diet
- Weight loss increases insulin sensitivity (more space in those fat cells!)
- Omega 3s seem to help decrease incidence and complications of type 2 DM
Exercise
- Exercising muscle doesn’t need insulin for glucose uptake
- Single bout of aerobic exercise increases insulin sensitivity for 48-72 hours
