Metabolism Effects Of Glucagon And Insulin Flashcards
Fed state vs fasting state
Fed state
- priorities are to maintain blood glucose levels and replenish lost glycogen and lipid/protein stores
- timing = 2-6 hrs after ingestion of a meal
- plasma = increased glucose/AA and TAGs
- pancreas increases insulin levels and decreases glucagon
- tissues increase synthesis of glycogen/TAGs and proteins
Fasting state
- priorities are to maintain blood glucose levels for brain and RBCs also mobilize FAs from adipose tissue and ketone bodies from liver for other tissues
- timing = >6-12 hrs after ingestion
- plasma = decreased glucose/AAs and TAGs
- pancreas increases glucagon levels but decreases insulin levels
- tissues degrade glucose/TAG and proteins
How does the insulin, glucagon and glucose levels correlate after a meal
1) immediately after a meal -> 60min
- glucose and insulin go up
- glucagon goes down
2) 60 -> 120 min
- glucose and insulin peak at 60 min and start to steadily decrease
- glucagon stays low and plateaus at 90min
3) 120 -> 240 min
- glucose and insulin continue to decrease and plateaus after 4hrs
- glucagon starts to increase around 4hrs after a meal
What catecholamine promotes glucagon production?
Epinephrine
- it shares the same metabolic effects as well
Carb metabolism regulation in liver in the presence of glucagon
1) high glucagon/insulin ratio causes elevated cAMP and increased levels of PKA in the liver
2) increased PKA activity favors phosphorylated form of PFK-2/FBP-2
- phosphorylated PFK-2 = inactive
- phosphorylated FBP-2 = active
3) active FBP-2 increases gluconeogenesis and glycogenolysis in the liver by converting F-2,6 BP into F6P which promotes gluconeogenesis
- decreases levels of F-2,6 BP
- increases levels of F6P )casues decreased inhibition of FBP-1 enzyme = Gluconeogenesis
4) increased levels of PKA also causes a build up of PEP which can be used in the gluconeogenesis pathway
all of this occurs in the cytosol of the liver cells
What are the inhibitors of glucagon
Hyperglycemia
Somatostatin
Insulin
Transscriptional regulation in liver based on insulin and glucagon levels
Insulin
- increases the following three enzymes in the glycolysis pathway
1) glucokinase
2) PFK
3) Pyruvate kinase - leads to build up of pyruvate via glycolysis**
Glucagon
- decreases the same three enzymes
- leads to a build up of PEP, F6P and glucose
- leads to a Build up of glucose with gluconeogenesis**
Hormonal regulation of glycogen enzymes
1) glycogen phosphorylase
- activated by epinephrine and glucagon (epinephrine more in muscle, glucagon more in liver)
- inhibited by insulin
2) glycogen synthase
- activated by insulin
- Inhibited by glucagon and epinephrine (epinephrine more in muscle, glucagon more in liver)
When is glucagon produced and degraded in muscles?
Synthesis = at rest
Degradation = during exercise
Signaling pathway for glucagon in liver cells
Binds to extracellular receptor Gs proteins and induces increased cAMP/AC
- requires epinephrine co-bound to B-adrenergic cells at the same time
Increased levels of cAMP causes cAMP-dependent protein kinase A to be upregulated which promotes phosphylation of glycogen phosphorylase kinase B (inactive) to phosphorylase kinase A (active)
Active Phosphorylase kinase A is used to degrade glycogen as well as inactivate glycogen synthase**
**insulin can inhibit two different areas of the cascade (both require insulin up-regulating protein phosphatase 1 enzymes)
- promotes glycogen phosphorylase kinase A -> B
- promotes cAMP-dependent protein kinase A -> B
(B is the inhibited form)
What are three lipolysis enzymes used in lipid metabolism
all three are upregulated by glucagon and epinephrine via cAMP levels and PKA activity
1) adipose triglyceride lipase (ATGL)
2) hormone-sensitive lipase (HSL)
- directly stimulated by glucagon**
3) monoglyceride lipase (MGL)
Each of these take a fatty acid of Triacylglycerol on lipid droplets and put it into the blood
this occurs in the fasting stat
Protein metabolism regulation with respect to high insulin/glucagon ratio
Activates AKT which inhibits TSC1/2 enzymes which activate Rheb-GTP enzymes.
End goal is to upregulate mTOR complex which induces translation and transcription of proteins and leads to increased protein synthesis
Glucagon in the liver on protein metabolism
Promotes AA uptake in the liver and upregulates expression of urea cycle and gluconeogenesis enzymes to catabolize the AAs into
- urea + energy (2 ATP)
- glucose
What are considered the counter regulatory hormones to insulin
Glucagon
Epinephrine and norepinephrine
Glucocorticoid
Growth hormone
Thyroid hormone
Somatostatin
Overall effects of insulin and glucagon on liver, adipocytes and skeletal muscles
Insulin
1) liver:
- uptakes glucose and amino acids.
- Produces LVDL particles
2) Skeletal muscles:
- uptakes glucose and amino acids
- produces glycogen and protiens
3) Adipocytes:
- uptakes glucose and VLDL from liver
- produces TAGs (fat synthesis)
- prevents degradation
Glucagon
1) liver
- promotes uptake of AAs
- catabllizes AAs and glycogen into glucose and secretes it out
- prevents FA production in liver
- promotes ketogenesis
2) Adipocytes
- promotes breakdown of TAGs into FAs (tissue lipolysis and secretes them into blood
3) skeletal muscle = no effects**
Catecholamine metabolic effects
Suppresses insulin secretion
Mobilizes glucagon secretion from a-cells
Promotes:
- lipolysis in adipose cells = free FAs and glycerol
- glycogenolysis in muscles and generates pyruvate and lactate
- glycogenolysis in liver to produce glucose
