Interorgan Metabolism Flashcards
fuel homeostasis
-taking in excess calories -> storage
-taking in too few calories -> nutrient release
factors that control fuel homeostasis
1) tissue fuel metabolism (gluconeogenesis, glycogenolysis, glucose sparing, etc)
2) pancreatic hormones (insulin and glucagon)
what cell type can ONLY use glucose as an energy source
red blood cells (RBCs)
glucose sparing effect
saving glucose for utilization by RBCs by using other forms of energy (ketone bodies, etc) when glucose is short
well-fed state
-high insulin levels (from beta cells) due to high levels of nutrients (glucose, amino acids, fatty acids)
-low glucagon
-stable glucose levels
-fatty acid and ketone body utilization are low
organ metabolism in well-fed state
insulin regulates tissues:
-muscle: glycogen & protein synthesis
-liver: glycogen & triglyceride storage
-adipocytes: triglyceride storage
calories stored in glycogen
2000 calories (can be used for glucose)
calories stored in proteins
30,000 calories (can be used to make glucose and/or ketone bodies)
calories stored in triglycerides
140,000 calories (fatty acids can be used to make ketone bodies; glycerol can be used to make glucose)
overnight fasting state
-low insulin (because low nutrients)
-high glucagon [turns on glycogenolysis, lipolysis, and gluconeogenesis]
-glucose stable
-slightly increased fatty acid utilization
-slightly increased ketone utilization
during overnight fast, what is the PRIMARY energy source
glycogen stores (~80% of energy)
[small amounts from amino acids and glycerol]
1-3 day fast
-low insulin
-high glucagon
-stable glucose
-significantly increased fatty acid utilization
-significantly increased ketone utilization
during 1-3 day fast, what is the PRIMARY energy source
glycogen stores are depleted, so… primary stores from proteolysis (releases amino acids for gluconeogenesis); triglyceride breakdown in fat and ketone body synthesis in liver increase too
prolonged fasting state
-low insulin
-high glucagon
-stable glucose
-fatty acid utilization WAY up
-ketone body utilization WAY up
-turned off proteolysis so we don’t waste away
during prolonged fasting, what is the PRIMARY energy source
ketone bodies
-glucose is preserved for RBCs (glucose sparing effect)
-muscle proteolysis is shutdown
how does the kidney contribute during prolonged fasting state
1) promotes reuptake of ketone bodies (conserves them)
2) can contribute to some gluconeogenesis
overview - how does insulin regulate gene expression in the liver
*insulin suppresses transcription of gluconeogenic enzymes in the liver during a well-fed state
details - how does insulin regulate gene expression in the liver
1) insulin binds its receptor and the activated receptor interacts with IRS
2) IRS binds to and activates a kinase
3) the kinase PHOSPHORYLATES FOXO
4) phosphorylated FOXO cannot enter nucleus and activate transcription of gluconeogenic enzymes
overview - how does glucagon regulate gene expression in the liver
*glucagon promotes transcription of gluconeogenic enzymes in the liver during a fasting state
details - how does glucagon regulate gene expression in the liver
1) glucagon binds its receptor
2) cAMP levels increase
3) cAMP activates PKA
4) PKA enters nucleus
5) C subunit of PKA phosphorylates CREB
6) CREB interacts with several transcription factors, including FOXO, which ACTIVATE TRANSCRIPTION OF GLUCONEOGENIC ENZYMES
CREB
cAMP response binding protein; interacts with FOXO to activate transcription of gluconeogenic enzymes in a fasting state (when glucagon is present)
type I diabetes characteristics
beta cells are destroyed, eliminating production of insulin; ketoacidosis is an acute complication
-frequently undernourished at onset of disease
-moderate genetic predisposition
-insulin always necessary
type 2 diabetes characteristics
insulin resistance, combined with inability of beta cells to produce appropriate quantities of insulin (but some insulin still present); hyperosmolar state is a complication
-obesity at onset of disease
-VERY STRONG GENETIC PREDISPOSITION
-responsive to oral hypoglycemic drugs; insulin may not be necessary
why is gluconeogenesis elevated in diabetes
insulin is not present to turn off transcription of gluconeogenesis enzymes (not phosphorylating FOXO); gluconeogenesis continues to make glucose, even in well-fed state, causing excess hyperglycemia
ketoacidosis in type 1 diabetes
1) glucagon is dominant over insulin
2) *glucagon stimulates hormone sensitive lipase in the adipocytes
3) free fatty acids and glycerol released into blood
4) liver converts FFA to ketones & carnitine is elevated
5) ketones released into blood and attain high levels
6) protons released and pH starts to drop
why is ketoacidosis a factor in T1D and not T2D
in T1D, the complete lack of insulin prevents glucose from being transported into cells, causing increased production of ketone body formation
-in T2D, there is still some insulin present so the glucose can still get into muscle and fat cells, decreasing likelihood of ketoacidosis
hyperosmolar syndrome in type II diabetes
high concentrations of glucose and electrolytes in blood cause water to move from tissues into blood, causing dehydration of tissues and brain
can diet and exercise reduce HbA1c levels
YES
HbA1c
-glucose forms a covalent bond with Hb (glycates Hb) when it is found in high concentrations
-higher glucose levels cause more adduction and elevated HbA1c
advanced glycation end products (AGE)
1) glucose converted to a reactive derivative
2) it reacts spontaneously with cellular proteins and forms covalent complexes
3) the protein is altered such that they bind and form cross-linked structures (ECM is especially vulnerable)
*lowers the elasticity of blood vessel walls and impedes normal blood flow
advanced glycation end products (AGE) and kidney
glycation of the glomerulus prevents the filtration system from working, which can lead to kidney failure
*problematic for diabetes patients due to excess glucose in circulation
how does metformin help diabetes
suppresses transcription of gluconeogenesis enzymes (PEP-carboxykinase and glucose-6-phosphatase) and reduces hepatic glucose output
