Endocrine Pancreas Flashcards
describe the cellular composition of the islets of Langerhans; include the hormone product of each cell type
alpha cells: 25%, secrete glucagon
beta cells: 60%, secrete insulin
delta cells: 10%, secrete somatostatin
F cells/pancreatic polypeptide cells: <5%, secrete pancreatic polypeptide
describe pancreatic hormone secretion, generally (blood flow)
endocrine pancreas has 10x more blood flow than the exocrine pancreas;
hormones flow from the pancreatic vein to the portal vein and then to the liver
describe insulin synthesis; including the importance of zinc
- beta cells make pre-proinsulin, which is cleaved to proinsulin
- proinsulin is 3 AA chains (A, B, C chains) connected by disulfide bonds that is cleaved in the golgi apparatus to form insulin
- insulin is 2 AA chains (A and B chains) connected by disulfide bonds)
- insulin (with is A and B chains) and a connecting peptide (C chain) are packaged in secretory granules, where insulin forms dimers (pairs up for stability)
- in the secretory granules, proton pumps keep the pH low to promote crystallization of insulin into a hexamer
- ZnT8 transporters pump zinc into molecules which promotes further crystallizationinsulin hexamer is composed of 6 insulin monomers and 2 zinc molecules; and is the crystallized storage form of insulin in the secretory granules
- insulin hexamer is composed of 6 insulin monomers and 2 zinc molecules; and is the crystallized storage form of insulin in the secretory granules
zinc-containing hexamers are often the form of insulin used for exogenous administration because, thanks to zinc, hexamers are more stable and have delayed absorption that prolongs the duration of insulin
summarize the process of glucose sensing, including the membrane glucose transporter involved (6)
- glucose enters beta cells through insulin-independent GLUT2 transporters
- glucose is converted to ATP in the beta cells
- high ATP concentrations closes potassium channels in the membrane of beta cells
- the closing of potassium channels leads to depolarization of beta cell membranes
- depolarization causes calcium channels in beta cells to open and calcium rushes into the cell
- calcium influx stimulates insulin secretion
note: some zinc is released with insulin, but its role is not fully understood; might have paracrine function of alpha cells to decrease glucagon secretion, and portal delivery to liver might decrease hepatic insulin uptake, but not fully sure!
describe the process of stopping insulin secretion (6)
direct reverse of insulin secretion!
- GLUT2 is still open, but less glucose influx leads to
- decreased ATP concentrations, which
- closes potassium channels, which will then
- repolarize the beta cell membrane and
- close calcium channels and the resulting lack of calcium influx will result in
- decrease in insulin secretion
what is a normal blood glucose reading for most species? are values outside this range always indicative of an issue?
80-120mg/dL
if slightly above or below could indicate pre or post meal, not always an issue as long as the body has the ability to return to normoglycemia
describe the overall action of insulin, give 5 functions, and say what stimulates and decreases insulin levels
overall anabolic/storage hormone
functions are:
1. inhibit gluconeogenesis
2. inhibit glycogenolysis
3. promote glycogen storage
4. stimulate glucose uptake by cells from blood
5. decreases glucagon secretion
stimulated by: hyperglycemia
decreases in response to: decrease in plasma glucose
describe the overall action of glucagon, give 2 functions, and say what stimulates and decreases glucagon levels
overall catabolic/breakdown hormone
functions:
1. stimulates breakdown of glycogen
2. promotes gluconeogenesis
stimulated by: hypoglycemia
decreases in response to: a rise in plasma glucose
describe the 2 types of insulin secretion
- basal: continuous secretion at low levels to prevent breakdown of energy stores
- bolus: intermittent, following a meal to prevent glucose spikes
what stimulates (4) and inhibits (2) insulin secretion?
stimulation:
1. glucose
2. CCK
3. amino acids (arginine and leucine)
4. incretins: glucose-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)
inhibited by:
1. catecholamines
2. somatostatin
explain how receptor binding causes insulin effects
- insulin circulates as free, unbound hormone and its active form is a monomer with a very short half life
- on its own, insulin cannot enter cells; it must bind to a surface insulin receptor, but can bind and unbind the receptors, meaning it can return to circulation to bind more cells and receptor activation induces effects
- insulin receptors have 4 subunits: 2 alpha outside the cell and 2 beta inside the cell that are linked by disulfide bonds and contain tyrosine kinase domains
- insulin bonds alpha subunit to cause conformational change, then beta unit is autophosphorylated, resulting in tyrosine kinase activation to activate insulin response substrates that set off a chain of events downstream
list 5 actions of insulin
main: facilitates nutrient uptake into cells
specific:
1. conversion of glucose to glycogen as a stored energy source (ATP)
2. conversion of fatty acids into triglycerides as an alternative energy source
3. use of amino acids for protein synthesis
also:
4. promotes cell growth and proliferation: is a potent mitogen and promotes protein synthesis; works synergistically with IGF-1, GH, platelet derived growth factor, and epidermal growth factor
5. increases cell membrane’s permeability to potassium and phosphorous, moving the ions from the extracellular space to the intracellular space
6. inhibit hormone sensitive lipase, activate lipoprotein lipase
give insulin-independent transporters, and the list and describe an insulin-dependent transporter
insulin-independent: GLUT 1,2, 3,5 and SGLT 1 and 2
insulin-dependent: GLUT4, found in striated (skeletal and cardiac muscle) and adipocytes; some are on the membrane, but most are stored in vesicles and transported to the membrane after binding of insulin receptors (insulin-dependent)
explain how skeletal muscle utilizes glucose for energy, including which transporter is used
insulin-dependent:
during meals! muscles will carb-load:
the meal provides glucose to bloodstream, the glucose promotes insulin release, then muscle cells use GLUT-4 to allow glucose into the cells and in the presence of insulin, storage is promoted and glucose is converted to glycogen for storage and saved for later
insulin-independent: between meals!
physical activity requires energy, triggering stored glycogen to be broken down into glucose that is then metabolized into ATP for cellular energy!
is there such a thing as too much insulin in the muscle and liver?
in the muscle, no!
in the liver: yes!
the liver can store glucose as glycogen until glycogen stores are full and then glucose is added to free fatty acids and converted to triglycerides that are incorporated into transport molecules like VLDL that are sent into circulation; VLDL is bad cholesterol and can build up in arteries and triglycerides can be delivered to adipose stores, leading to obesity
