Flashcards in Metabolic Homeostatis Deck (33)
What occurs with starvation?
-Activation of HPA axis
-Dysregulation of growth hormone and IGF-I
What is the initial energy source for the brain?
80% from fat stores, release of FFAs, breakdown of liver glycogen, breakdown of proteins
What is the energy for the brain in a prolonged fast?
Ketone bodies used as energy source for brain with reduced reliance on glucose as fuel source
What is syndrome X?
It is a metabolic syndrome often combined with obesity and diabetes.
What are the four factors of syndrome X?
-Dyslipidemia – TGs > 150 mg/dl, HDL
What is the primary hormone produced by adipose tissue?
What is the function of Sterol regulatory binding protein 1C (SREBP-1C)?
Promotes TAG synthesis
Activated by lipids and insulin
Increases glucokinase “trapping” glucose inside cells.
What is the function of PPARgamma?
Nuclear steroid hormone receptor
Regulates TG storage and adipocyte differentiation
What is the function of PPARgamma agonists?
PPARγ agonists used to treat insulin resistance and Type 2 diabetes mellitus
What is the side effect of PPARgamma agonists?
What is the relationship between leptin and total fat?
What is insulin resistance?
Insulin does not efficiently transport glucose into cells -> due to constant high glucose levels and high insulin levels
What can beta cell exhaustion cause in diabetes patients?
Conversion from Type II to Type I
What is the main diagnosis factor for diabetes type II?
Elevated HbA1C - shows the glycosylation of RBCs which is over a longer period of time
What are the main symptoms of diabetes mellitus type II?
What is the mechanism of sulfonylureas in treating DM Type II?
Close ATP-dependent K+ channels in beta cells causing insulin release
What is the function of biguanides like metformin in treating DM Type II?
Inhibits hepatic gluconeogenesis
Increases insulin receptor activity making cells more sensitive to insulin, increased glucose uptake
What is the cause of DM Type I?
Destruction of pancreatic beta cells – causes insulin dependence
What is found in untreated DM Type I?
How does diabetic ketoacidosis occur?
Decreased insulin ->
Increased counter regulatory hormones ->
Increased FFA release – hepatic precursor for ketone acids ->
Ketone metabolism ->
Increases blood [H+] ->
Prolonged increased acidity will lead to ketoacidosis and then coma
Does ketogenesis occur in absolute insulin deficiency, like Type I DM?
Does ketogenesis occur in relative insulin deficiency, like Type II DM?
Describe insulin and GH function in the fed state.
The presence of insulin with a mixed meal will lead to GH release which will stimulate IGF-I which will increase glucose uptake in muscle and inhibits proteolysis.
GH opposes lipgenesis of insulin
Describe insulin and GH function in the starvation state.
No insulin with low glucose and glucagon is stimulated as insulin is not there to inhibit it. GH will increase due to AAs from increased proteolysis.
No IGF-I with no insulin so there is no negative feedback on GH.
Describe insulin and GH function in DM Type I.
No insulin but there is HIGH glucose since the patient is eating. Glucagon is stimulated without inhibition though with no insulin.
GH will be increased with increased proteolysis with no negative feedback due to no IGF-I.
Describe insulin and GH function in DM Type II.
Low insulin or insulin is not receipted.
HIGH glucose with glucagon stimulated but it is inhibited since insulin is present. Presence of insulin also inhibits ketogenesis.
What are the risk factors for Type II DM?
Impaired beta cell proliferation during childhood
Increased propensity for insulin resistance
-High caloric diet
-Lack of physical activity
When does islet cell development begin and end?
Islet neogenesis occurs during embryonic development and beta cell replication continues during childhood/adolescence but is stable in adults
What gene is important for both islet neogenesis and beta cell proliferation?