What are the effects on:
By Insulin and Glucagon?
How is glucose utilized during strenuous exercise?
Utilization of glucose by muscle is matched by an increase in hepatic glucose production, mediated in large part by glucagon
--> prevents hypoglycemia and provides another adjustment vital to survival in "fight or flight" situations
How is glucose utilized during serious injury or shock?
- A prompt rise in glucagon occurs together with a relatively slow insulin level, bringing about "stress hyperglycemia"
--> maximizes glucose delivery to an under-perfused brain
What types of cells are in the Islet of Langerhans? What do they secrete?
Alpha = Glucagon
Beta = Insulin
Delta = Somatostatin (SRIF)
How does somatostatin (released by delta cells) affect other cells in the islet?
SRIF coordinates the secretion of both insulin (beta cells) and glucagon (alpha cells)
- it can inhibit release of either hormone
--> ALL actions of SRIF are inhibitory
What is the process of insulin biosynthesis?
1. Formation of insulin mRNA
2. Ribosomal translation: synthesis into proinsulin
3. Transfer of proinsulin to the golgi complex
4. Packing of proinsulin to golgi complex
5. Conversion of proinsuiln into insulin (posttranslational modification)
6. Formation of zinc-insulin crystals
7. Translocation of granules to beta cell membrane
8. Fusion of granul and cell membrane
9. Liberation of granule (exocytosis)
What conditions are associated with insulin resistance?
--> Decreased insulin binding occurs in:
Growth Hormone excess
What conditions are associated with Insulin hypersensitivity?
--> Increased insulin binding occurs in:
How does insulin regulate glucose uptake by cells?
Insulin activates a series of phosphorylations and dephosphorylations that result in increased expression of GLUT 4 transporters on the surface of the cell.
- After binding, insulin and its receptor are usually internalized, constituting an "off switch" for insulin activation
- Majority of internalized hormone undergoes enzymatic degredation in the lysosomes
What are the actions of insulin on the liver?
- Stimulate glucose intake and trapping of glucose via phosphorylation by glucokinase
- Promotes storage of glucose as glycogen by activating glucogen synthase
- Reduces glucose output by inhibiting gluconeogenesis
- Reduces glucose output by inhibiting glycogenolysis through decreasing glycogen phophorylase activity
- Reduces formation of ketone bodies by decreasing beta-oxidationg of FAs
What are the actions of insulin on muscle?
- Stimulates glucose and AA uptake
- Stimulates gluocse storage as glycogen
What are the actions of insulin on adipose tissue?
- Stimulate glucose and AA uptake
- Increase the formation of alpha-glycerophosphate for FA esterification and triglyceride storage
How does insulin promote storage of FAs?
- Accelerates uptake and storage of lipid in adipocytes by stimulating lipoprotein lipase (which converts triglycerides into free fatty acids which are able to enter adipocytes)
- Facilitates glucose uptake into adipocytes (becoming a 3C backbone for TG formation
- Enhances liver FA synthesis and TG release
- Dramatically inhibits hormonally sensitive lipases in adipocytes, further reducing blood levels of free FAs
- Inhibits conversion of FA to ketoacids in hepatocytes
What stimulates insulin release?
- GI hormones (i.e. Glucagon-like peptide-I)
- B2 adrenergic receptors - Epinephrine
What inhibits insulin release?
- a2 adrenergic receptor
What is the mechanism of B-cell insulin release when activated by glucose?
Glucose metabolism generates ATP
- ATP closes K+ channels resulting in depolarization, leading to Ca2+ channel opening
- Ca2+ mediates insulin release
What tissues does insulin NOT regulate glucose uptake?
- Peripheral neurons (including retina)
- Renal medullary cells
- Cells lining blood vessels
- Liver cells (though it does regulate glucose metabolism in the liver)
What hormones counter insulin?
Cortisol (works much slower than glucagon)
Epi & NE