diabetes phys review Flashcards
Review biochemistry- gluconeogenesis, glycogenolysis, lypolysis, ketogenesis
gluconeogenesis- generation of glucose from non- carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids. Liver major site.
Glycogenolysis- is the breakdown of stored glycogen to glucose- 6 phosphate and glycogen
Lypolysis: the breakdown of fats and other lipids by hydrolysis to release fatty acids
Ketogenesis: ketone bodies produced by the breakdown of fatty acids and ketogenic amino acids
Glycolysis- breakdown of glucose to form pyruvate with the production of 2 molecules of ATP
Glycogenesis- synthesis of glycogen, glucose molecules are added to chains of glycogen for storage
Islet of langerhans
Duct less,
Alpha cells- glucagon
Beta cells- insulin
Delta cells- somatostatin
Secrete their products into the blood
Insulin is a storage hormone
Meal– stimulates the pancreas to secrete insulin
Insulin tells cells to up take glucose (into glycogen), fatty acids into (fat), and amino acids int (proteins)
Human proinsulin is cleaved by golgi beta cells to form C peptide (a dn B chains) C peptide is a marker of Beta cell function
Glucose transporters
GLUT 1- basal glucose uptake, every where and the brain
GLUT 2- Beta cell glucose sensor, transport out of intestina and renal epithelial cells,
GLUT 3- basal glucose uptate- brain and placent
GLUT 4- insulin stimulated glucose uptake- muscle and fat
insulin receptor
insulin binds to the alpha subunit of its receptor– causes autophosphorylation of the beta subunit–> activates tyrosine acitivity.
The receptor tyrosine kinase activity begins a cascade of cell phosphorylation that increases or decreases the activity of enzymes– such as
GLUT transport to the cell membrane (GLUT 4)- regulated by glucose conc gradient
Glucose uptake
Muscle- glucose goes into muscle, and does not leave, only amono acids can leave muscle (to be used as gluconeogeneis)
Glucose can be converted to Fatty acids and uses keotnes
control of insulin secretion
Stimulators- glucose, amino acids, fatty acids, indirect- (Growth hormone/cortisol)
Amplifiers- GI hormones
Inhibitors- somatostatin (paracrine)
how is insulin released from a B cell
When theres a lot of glucose GLUT 2 lets it in
Glucose–> G6P via glucokinase–> increase in ATP–> closure of ATP K channel, K builds up
So the Ca channel opens up
The Ca leads to insulin release
Glucagon
increase glucose–> (from amino acids, fatty acids)
Build up of flucose
Amino acids turn on alpha cells (glucagon)
Glucose, insulin, somatostatin, ketones FFA inhibit alpha cells (glucagon)
so when you eat a lot of protein (And insulin therefore goes up), glucose is taken up by cells
But hypoglycemia is prevented by stimulating glucagon
glucagon like peptides
secreted from the gut in response to feeding
acute- increases insulin response to glucose
Chronic- increases beta cell mass
insulin goes down a few hours after a meal to prevent hyperglycemia because of the lowered stimulus from the gut and the increase in incretin (decreases blood glucose levels
diabetes mellitus
too much sweet urine
Type 1 DM- islet cell destruction
Type 2 DM- insulin resistance
Gestational diabetes Secondary hyperglycemia (acromegaly and cushings
Type 1 DM pathogenesis
Genetic susceptibility and environmental infection–> autoimmune attack of beta cells by lymphocytes and immunoglobulins–> loss of insulin secretion (permanent)
Pathogenesis of T2 DM
Primary cellular defect-> decreased glucose uptake (insulin resistance)
Primary Liver defect–> decrease in hepatic glucose uptake, failure to decrease gluconeogenesis
Relative beta cell defect–> inadequate insulin response (usually hyperinsulinemic)
all will lead to hyperglycemia (insulin resistance with increased insulin but decreased response to insulin
Hyperglycemia(insulin resistance with increased insulin but decreased response to insulin)
natural history of type 2 DM
Pt starts to gain weight
Insulin resistance gets worse and worse
The insulin secretion starts to go down
There is a point of no return
long term complication of DM
Retinopathy (blindness)
Nephropathy (dialysis/ transplant), neuropathy
CV disease, skin (poor wound healing)
Pregnancy- increased baby size- increased problems
