Pancreas Endo: Bridges Flashcards
Name the cell types in the Islets of Langerhans and name the hormones secreted by them.
Beta cells secrete insulin- serum glucose decr. (65-80% of cells in pancr)
Alpha cells secrete glucagon- serum glucose incr. (15-20% of cells in pancr)
Delta cells secrete somatostatin.
Gamma (PP) cells produce pancreatic polypeptide.
Epsilon cells produce Ghrelin. (also produced elsewhere)
Describe the main targets and functions of glucagon.
The main target of glucagon is the liver.
When glucose levels are LOW, alpha cells in the pancreas release glucagon. This promotes the breakdown of glycogen stores in the liver and muscle and the generation of glucose from gluconeogenic precursors. That being said, glucagon receptors exist mainly in the liver, so glucagon does not exert its main catabolic (gluconeogenesis) effects on either muscle or adipose tissue.
List the major factors that stimulate or inhibit glucagon and insulin.
::Low blood glucose stimulates glucagon secretion.
::Exercise also induces glucagon secretion by an unknown mechanism, possible simply due to exercise-induced depletion of glucose.
::High levels of plasma amino acids, such as after a protein rich meal, also stimulate glucagon AND insulin secretion.
::High blood glucose stimulates insulin release.
::glucose-dependent insulinotropic peptide (GIP), sympathetic and parasympathetic neurons, and circulating epinephrine also increase insulin secretion.
- vice versa for inhibition.
Describe the important physiological roles of insulin.
Main job: Reduce blood glu levels.
::promotes the uptake of glu from blood into muscle and adipose tissue.
::Enhances the synthesis of glycogen and triglycerides in the liver, adipose tissue, and muscle.
::Inhibits gluconeogenesis
::Promotes the breakdown of glucose via glycolysis
List the major actions of insulin in muscle, adipose tissue, and the liver.
::Liver:
- Insulin stimulates the liver to store glucose as glycogen.
- Insulin promotes synthesis of fatty acids in the liver.
::Adipose tissue:
- Insulin facilitates entry of glucose into adipocytes.
- Insulin inhibits breakdown of fat in adipose tissue via GLUT4.
::Muscle:
-Insulin facilitates entry of glucose into muscle cells via GLUT4.
Explain briefly the mechanism of glucose uptake into muscle.
Insulin binds to an RTK on the target cell surface which transautophosphorylates itself, generating binding sites for insulin receptor substrates, which are also then phosphorylated.
Phosphorylation of the insulin receptor substrates creates a binding site for PI3K which generates the key second messenger in insulin signalling, PIP3, which diffuses along the inner membrane and recruits two important PK’s: AKT and PDK1.
Most known functions of insulin are inhibited when PI3K is inhibited
* Once phosphorylated, AKT is the most important factor in regulating insulin function.*
::In both fat and muscle, AKT/PDK1 are ABSOLUTELY necessary for insulin stimulated glucose uptake. They are required to move GLUT4 to the plasma membrane from where it hangs out in the cytoplasm. GLUT4 is the channel across which glu diffuses passively into the cell.
Name the tissues in which insulin initiates glucose uptake and those in which glucose does NOT facilitate glucose uptake.
Insulin promotes glucose uptake by the muscle and adipose tissue and others, less important.
The brain, liver, and kidneys do not require insulin to promote uptake because they don’t use GLUT4 for uptake, but another transporter that is insulin independent.
List the major factors that stimulate or inhibit insulin secretion.
Incretins are enhancers of insulin release, typically released by the gut. GLP-1 and GIP1 are two of them.
The parasympathetic NS stimulates insulin release.
High levels of blood glu stimulate insulin release.
Low glu, low insulin.
Sympathetic NS, low insulin.
DPP-4 degrades incretins (GLP-1/GIP1), lowering insulin response.
Draw an oral glucose tolerance test (insulin, glucose, glucagon levels) and explain the conditions and describe what is occurring and why. Explain how the two hormones act to promote glucose homeostasis in the plasma and in the key target tissues for each of these hormones
Do it.
State which nutrient storages are preferably used for short-term regulation of energy metabolism if no nutrients are available from the GI tract.
Short term nutrient storage is glycogen, broken down by glycogen phosphorylase to glucose.
If not nutrients are available, gluconeogenesis is used, and in starvation, fatty acids are utilized.
Discuss the hormones involved, fuel storage capacity, fuel storage consumption, and glucose (or fatty acid) levels during:
1) the postprandial period
2) the post absorptive period
3) fasting
1) The postprandial period:
::Hormones involved- insulin rises, glucagon falls
::fuel storage capacity- glycogen, protein, lipids produced
::fuel storage consumption- No consumption of stores, creatine phosphate/glycolysis for energy.
::glucose (or fatty acid) levels- glucose levels high
2) The post absorptive period:
::Hormones involved- Glucagon, epinephrine, cortisol, and growth hormone all act to increase circulating glu, glycerol, and fatty acids.
::fuel storage capacity- trying to maintain glycogen stores
::fuel storage consumption- blood glucose is maintained by a combination of glucose production by the liver (gluconeogenesis/glycogenolysis) and a switch from glucose utilization to fatty acid and ketone utilization by most tissues
::glucose (or fatty acid) levels- glucose levels steady, fatty acid levels rising.
trying to save glucose for use by CNS
3) Fasting
::Hormones involved- insulin falls, glucagon falls, cortisol rises, growth hormone rises
::fuel storage capacity- Nothing is being stored
::fuel storage consumption- Ketones
::glucose (or fatty acid) levels- glucose levels LOW
List the insulin-counteracting hormones and their roles in glucose homeostasis. Discuss the hormones involved in minute-to-minute regulation and long term regulation of glucose homeostasis.
Epinephrine (adrenaline) stimulates glycogenolysis and gluconeogenesis in the liver as well as lipid release from adipose tissue and glucose oxidation in muscle.
*both glucagon and adrenaline function by stimulating adrenergic signaling and cAMP-dependent PKA activation.
Glucagon, epinephrine, cortisol, and growth hormone all exert effects on carbohydrate and lipid metabolism that are opposed, in one way or another, to those of insulin. They raise plasma concentrations of glucose, glycerol, and fatty acids.
Insulin and glucagon are minute-to-minute regulators.
Cortisol and growth hormone are long term regulators, being elevated during times of growth or stress to ensure that organs like the brain are getting adequate supplies of glucose during a prolonged fast. They maintain blood glucose levels at appropriate levels by stimulating glucose release and production by the liver.
How does glucagon stimulate gluconeogenesis via transcription of new genes?
v plasma glu –> ^glucagon –> ^ PKA –> phosphorylation of CREB –> translocates to nucleus —> ^ transcription of proteins necessary for gluconeogenesis
What effect do the sympathetic and parasympathetic nervous systems have on insulin and glucagon levels?
Sympathetic= more glucagon, less insulin (fight/flight, use energy) Parasympathetic= more insulin, less glucagon (rest/digest, store energy)
