Phys of Endocrine Pancreas Flashcards
What is the primary fuel for the body?
glucose
What is glucose stored as?
glycogen
Organs where glycogen is stored. (2)
- liver
- muscle
insulin is what type of hormone?
anabolic
What does it mean that insulin is an anabolic hormone?
it promotes the building of tissue stores
How can protein be used as an energy source?
amino acids can be changed to glucose in the liver and then used or stored as glycogen
gluconeogenesis
creating new glucose
glycogenolysis
the break down of glycogen stores
glycogenesis
formation of glycogen from sugar
glycolysis
breakdown of glucose
normal fasting blood glucose range
70-99 mg/dL
normal plasma postprandial glucose range
no higher than 140 mg/dl
what are the 4 counter regulatory hormones to insulin?
- glucagon
- epinephrine
- cortisol
- growth hormone
primary action of glucagon
- the major counter to insulin
- released when glucose concentrations fall too low
- exerts effect on liver to break down glycogen stores and release glucose into the blood rapidly
- predominant during fasting states
primary action of epinephrine
- stimulates the release of hepatic glucose via glycogenolysis and lipolysis
- released during periods of stress and emergency
primary action of cortisol
- stimulates hepatic uptake of amino acids
- can be used to make new glucose
primary action of growth hormone
- increase lipolysis
- inhibit glucose uptake at the muscle and adipose tissue
what are the 3 target organs of insulin action?
- liver
- muscle
- adipose tissue
(also the brain)
action of insulin on the liver
- liver is the first organ reached by insulin after being released into the portal circulation
- 2 main actions:
1. simulate the uptake of glucose by the liver
2. stop the breakdown of glycogen by changing the enzymes in the glycogen synthesis pathway
-therefore, insulin stimulates glycogenesis, fatty acid synthesis, and triglyceride production and inhibits glycogenolysis, gluconeogenesis and ketogenesis
knowing the action of insulin on the liver, what happens at the liver when insulin levels are low?
the liver releases glucose from glycogen to maintain blood glucose w/i normal limits
action of insulin on the muscle
- stimulates the uptake of glucose and amino acids by the muscle cells
- promotes protein synthesis by increasing amino acid transport and stimulating ribosomal protein synthesis
- it also promotes glycogen synthesis to replace glycogen storage used during muscle activity
action of insulin on the adipose tissue
- stimulates glucose and fatty acid uptake leading to lipogenesis
- it inhibits lipolysis
what portion of the pancreas contains the exocrine cells?
head
what portion of the pancreas contains the endocrine cells?
tail
beta cells produce ?
insulin
alpha cells produce ?
glucagon
delta cells produce ?
somatostatin
define insulin
- protein made up of 51 amino acids
- it’s a polypeptide whose genetic code is in the DNA located in the cell nucleus
- produced by the beta cells of the pancreas
- stored in the form of proinsulin in vacuoles until released
define proinsulin
- precursor to insulin
- polypeptide of 86 amino acids
- produced and stored in secretory granules (made by Golgi)
define C peptide
- the counter part of insulin that is produced when proinsulin is cleaved
- it has no biological activity but is still released into the portal vein in equimolar amounts to insulin
- therefore is easy to measure
define basal insulin
- the insulin that is secreted by the pancreas at all times
- it helps the peripheral tissues take up glucose during fasting periods
first phase of insulin release from the pancreas
- quick rise in insulin concentrations in response to rising glucose concentrations
- the readily available insulin is rapidly depleated
- the rapid rise in insulin goes directly to the liver to signal it to quit breaking down glycogen
- so, first phase = decrease in hepatic glucose production
second phase of insulin release from the pancreas
- somewhat delayed
- represents a more slowly mobilized pool of insulin in the beta cells
- the insulin not taken up by the liver enters the peripheral circulation where glucose is entering from the intestines
- they travel together until they reach muscle and adipose tissue
what happens to glucose in a fed state?
- it is absorbed from the intestines and enters the blood stream
- increase in glucose concentration stimulates the release of insulin from beta cells
- as glucose reenters circulation of the GI tract, insulin acts to restrain the rise in blood glucose concentration
what happens to insulin in the fed state?
- insulin release is stimulated by rising glucose concentrations
- it then uses two processes to keep the blood glucose concentration from rising:
1. suppression of hepatic glucose output
2. stimulation of glucose uptake via muscle and liver
overview summary of insulins action in the fed state
- suppress hepatic glycose production
- stimulate glucose uptake by peripheral tissues
- suppress glucagon release
- muscle uptake of glucose
- decrease in lipolysis and increase in lipogenesis
- increased amino acid uptake by muscles leading to increased protein synthesis
action of insulin in a fasting state
- glucose concentrations fall resulting in a decrease in the plasma insulin concentration
- 80% glucose disposal happens in non-insulin dependent tissues (brain, blood, neurons, etc.)
- remaining 20% of glucose metabolism occurs in the liver, muscle, and adipose
- inulin is released in a pulsatile pattern throughout the day when a person is not eating (basal insulin)
action of glucagon in a fasting state
- glucagon is secreted by pancreatic alpha cells to oppose the action of insulin and stimulate hepatic glucose production and glycogenolysis
- glucagon promotes availabilyt of energy in the form of glucose from glycogen and ketones
what is the relationship b/w glucagon and insulin?
- they are closely linked
- one increases while the other decreases to keep plasma glucose levels normal
describe the interaction of insulin w/ its receptor
- receptor is on target tissues cell membrane
- has alpha and beta subunits
- insulin binds alpha unit which activates the beta subunit
- result is recruitment and phosphorylation of intracellular substrates
- triggers a cascade of events in the cells leading to activation of GLUT4 moving to cell membrane, binding with extracellular glucose and transporting it into the cell
what is the role of the liver in the metabolism of insulin?
- liver removes 50% of insulin on first pass
- liver is major site of endogenous insulin elimination
what is the role of the kidneys in the metabolism of insulin?
- 2nd major site of insulin metabolism next to the liver
- in those w/ renal insufficiency or failure, the half life of insulin will be prolonged
action of glucagon
- secreted as insulin levels fall
- inhibited by glucose
- major target organ = liver
- stimulates breakdown of glycogen stores to maintain glucose levels during fasting state
action of somatostatin
- produced by delta cells
- inhibits secretion of many other hormones
- in pancreatic islet: inhibits secretion of insulin and glucagon
action of amylin
- co-packaged and co-secreted w/ insulin from beta cells
- helps regulate postprandial glycemia by suppressing postmeal glucagon secretion of alpha cells
- helps coordinate storage of carbs to transfer triglyceride into muscle glycogen in skeletal muscle
describe the incretin effect
- incretins = GLP-1 and GLP-2
- GLP-1: produced by L cells in the intestines after a meal
- stimulates the production of insulin and inhibits secretion of glucagon; inhibits gastric emptying; inhibits appetite and induces weight loss
- GLP-2: stimulates nutrient absorption at the intestines
enzyme that inactivates incretins
depeptidyl peptidase IV (DPP-IV)
effect of PSNS on insulin secretion
- stimulates insulin secretion
- “cephalic phase”
- sensory stimuli and neural inputs are activated when food is eaten or anticipated
- Vagus nerve activation –> stimulates insulin secretion
effect of SNS on insulin secretion
-inhibits insulin secretion
