Diabetes Flashcards
What is diabetes mellitus?
Insufficiency of insulin signalling relative to the requirements of the tissues for this hormone
What are some symptoms of diabetes?
Polyuria, polydipsia, polyphagia
Elevated fasting blood sugar, ketosis, weight loss
What are the normal and diabetes serum glucose levels?
Normal: 4.4-6.1 mmol/L
Diabetes mellitus: >7.0 (fasting plasma glucose), >11.1 (plasma glucose 2 hours after 75g glucose)
What is type 1 diabetes?
Autoimmune destruction of beta cells of the pancreas (no insulin in body)
Insulin dependent diabetes, juvenile onset, thin or normal weight
What is type 2 diabetes?
Strong genetic link with insulin resistance or insulin deficiency (later on)
Non-insulin dependent diabetes, mature onset, obese
How is type 2 diabetes treated?
Healthy diet and increased exercise
Hypoglycemic tablets
Insulin injections
What are beta cells like in a resting state?
Normal glucose levels go through GLUT2 and are sensed by the mitochondria
ATP is used to open a K channel and let K out of the cell which hyperpolarized state to not open the voltage gated Ca channel and not release insulin
What are beta cells like in a glucose stimulated state?
High glucose levels outside of the cell goes through GLUT2 and is sensed and metabolized by the mitochondria to increase ATP and close the K channel which depolarizes the cell and opens the voltage gated Ca channel so it can rush in and allow for the release of insulin
What is GLUT4?
GLUT4 is the insulin dependent transporter.
GLUT2 is insulin independent
How does insulin affect GLUT4 and GLUT1/2?
GLUT4 has increase uptake of glucose in skeletal muscle, cardiac muscle, smooth muscle, mucosa, adipose tissue, leukocytes, pituitary
GLUT1/2 is not affected in the brain, kidney, intestines, liver, RBC, endothelium, pancreas
What are the defects in glucose levels in those with diabetes?
Increase in extracellular glucose
Decrease in intracellular glucose (tissues with GLUT4)
Increase in intracellular glucose (tissues with GLUT1/2)
What occurs in insulin resistance?
Receptor and post receptor defects
Increased glucose production by liver, insufficient glucose disposal in peripheral tissues and impaired insulin secretion (affects liver and peripheral tissue)
How can the insulin receptor become insensitive in type 2 diabetes?
Cytokines (phosphorylate IRS1/2) and fatty acids inhibit IR signalling by insulin to activate GLUT4
What are the effects of insulin on the liver and muscle?
Liver: Inhibits glycogenolysis, inhibits conversion of amino acids to glucose, promotes glucose storage as glycogen
Muscle: Increased protein and glycogen synthesis
What causes a coma from insulin signalling deficiency?
Decreased glucose uptake causes hyperglycemia, glucosuria
Increased protein catabolism causes increased nitrogen and amino acid loss in urine
Increased lipolysis causes increased free fatty acids, cholesterol and ketone bodies
All cause electrolyte depletion which causes dehydration and thus coma
What are the complications of diabetes?
Blood vessels (heart disease, stroke, hypertension) Retinopathy, nephropathy, neuropathy
How is insulin synthesized?
Preproinsulin is converted to proinsulin when the signal sequence is cut off, then proinsulin is converted to insulin when chain C is cut out, leaving chain A and B
What is an example of rapid acting insulin? How long does it take to work?
Insulin Lispro, Insulin Aspart
onset in 10-30 minutes lasts 3-5 hours
What is an example of short acting insulin? How long does it take to work?
Regular novolin R (crystalline Zn)
Onset in 30 minutes to 1 hours and lasts 4-12 hours
What is an example of intermediate insulin? How long does it take to work?
NPH/Humulin N
Onset is 1-2 hours and lasts 10-20 hours
What is an example of mixture insulin? How long does it take to work?
Humalog mix
Onset is 10-30 minutes and lasts 14-24 hours
What is an example of long acting insulin? How long does it take to work?
NPH/Regular, insulin glargine (no peak), insulin detemir (no peak)
Onset is 0.5-1 or 1-4 hours and lasts 18-24 hours
What are rapid acting insulins?
Analog of human insulin in which amino acids 28 and 29 in the beta chain are reveresed and reduces antiparallel dimer formation
More closely resembles insulin response to a meal
Pharmacokinetics differ from normal insulin
How should rapid acting insulin be taken?
Take 15 minutes prior to a meal
Can be used by both Type 1 and Type 2