Endocrine Pancreas Flashcards
What two substances work together to regulate blood glucose after a meal and during fasting?
insulin and glucagon
What part of the endocrine pancreas is responsible for synthesizing hormones?
pancreatic islets of langerhans
What cells of the endocrine pancreas produce insulin?
beta cells
Where are beta cells located?
most are in center of islet
What cells of the endocrine pancreas produce glucagon?
alpha cells
Where are alpha cells located?
most are around outer rim of islet
What cells of the endocrine pancreas produce somatostatin?
delta cells
Where are delta cells located?
interspersed around beta and alpha cells
What connects alpha cells to each other, beta cells to each other, and alpha cells to beta cells?
gap junctions
What allows for communication among islet cells?
- gap junctions
- blood supply
- innervation by adrenergic, cholinergic, and peptidergic neurons
What was the first hormone isolated from animal sources, first to have structure determined and mechanism of action described?
insulin
Which hormone has an amino acid sequence that varies by species with certain segments highly conserved within vertebrates?
insulin
Insulin is synthesized as preprohormone with what 4 peptides?
- signal peptide
- A and B chains
- C chain (connecting peptide)
What is the structure of insulin?
peptide hormone with 2 chains (A chain and B chain) and 3 disulfide bridges
What do the three disulfide bridges of insulin link?
- 2 brdiges link A and B chains together
- third bridge is within the A chain
Describe the steps to synthesize insulin.
- synthesized as preprohormone with four peptides
- proinsulin sent to ER, insulin folds and disulfide bridges form
- golgi packages into granules, proteases cut C-peptide
- secretion via exocytosis
The most important stimulator of insulin secretion is what?
blood glucose
Describe regulation of insulin secretion.
- transport of glucose into beta cell via GLUT 2 transporter (facilitated diffusion)
- glucose immediately phosphorylated by glucokinase – ATP is a product
- ATP closes ATP sensitive K channels – depolarizes membrane
- depolarization opens voltage gated Ca channels – Ca flows into cell, inrceasing intracellular Ca
- increase in Ca causes exocytosis of insulin granules into venous blood
Does oral or IV glucose cause greatest response due to an “incretin” effect?
oral
What substances other than blood glucose stimulate insulin secretion?
- amino acids
- ketoacids
- FFA
- K+, Ca
- GIP, vagal stimulation (Ach), drugs (sulfonylurea drugs)
- glucagon
What substances other than blood glucose inhibit insulin secretion?
- fasting
- exercise
- somatostatin
- leptin
Describe the mechanism of action of insulin in peripheral cells.
- insulin binds alpha subunits, causes conformational change, activates tyrosine kinase in beta subunits
- tyrosine kinase phosphorylates other proteins/enzymes involved in physiologic actions of insulin
- insulin receptor complex internalized by target cell to be degraded, stored, or recycled
Tyrosine kinase (insulin receptor) has four subunits. Where are they?
2 alpha subunits extracellular
2 beta subunits span the mmebrane, have tyrosine kinase on intracellular side
What are the actions of insulin?
- when nutrients are available, insulin makes sure those nutrients are stored
- insulin directly stimulates glucose uptake into muscle and fat, but not liver
How does insulin store nutrients?
- glucose stored as glycogen in muscle and liver
- FFA stored as adipose tissue
- Protein stored in muscle
What glucose transporters are insulin independent?
- GLUT 1 found in brain, RBC
- GLUT 2 found in liver, beta cells of pancreas
- GLUT 3 found in brain
What glucose transporters are insulin dependent?
- GLUT 4 found in fat, muscle, heart
Transport of glucose in intestine and kidneys is NOT regulated by insulin, but is ____ dependent and carried out by what transporter?
- Na dependent
- GLUT 5 transporter in intestine
What are the effects of insulin on carbohydrate metabolism?
- decreases blood glucose
- increases glucose transport into muscle and adipose
- promotes glycogen formation in liver and muscle
- inhibits gluconeogenesis and glycogenolysis
What are the effects of insulin on lipid metabolism?
- inhibits mobilization and oxidation of FA
- inhibits ketogenesis in liver
- promotes FFA storage as triglycerides
- inhibits FFA uptake in muscle
- inhibits lipolysis
What are the effects of insulin on protein metabolism?
- overall anabolic
- decreases blood AA
- increases AA and protein uptake by tissues
- increases protein synthesis
- inhibits protein degradation
What are other general effects of insulin not related to a specific metabolism?
- promotes K+ uptake into cells by increasing activity of Na/K ATPase
- promotes phosphate, Mg++ uptake into cells
- insulin decreases appetite via the satiety center of hyothalamus
- excess insulin causes hypoglycemia which stimulates cortisol release to increase appetite
What acts as a protective mechanism during acute illness to preserve brain’s glucose supply?
insulin resistance
Insulin resistance can occur via alterations in what?
insulin receptors
(either by decreasing number of receptors or decreasing affinity of receptors for insulin)
What is insulin resistance?
- when cells fail to respond normally to insulin
- insulin overproduced: blood insulin and glucose remain high
What can cause insulin resistance other than alterations to insulin receptors?
- hormones (cortisol, GH, thyroid hormones, epilepsy, estrogen/progesterone)
- obesity
- liver or kidney failure
- sepsis
- insulin antibodies
What pathophysiology is associated with insulin?
- diabetes mellitus (type 1 and 2)
- insulinoma
Type 1 diabetes mellitus is due to what?
insulin deficiency
Type 2 diabetes mellitus is due to what?
insulin resistance
Insulinoma results in what?
excessive insulin production by beta cell tumor
What can result from lack of insulin or lack of insulin action?
- hyperglycemia
- hyperlipidemia
- peripheral tissue protein catabolism
True or false: glucagon sequence is identical in all species.
true
What stimulates glucagon release?
- hypoglycemia
- protein/AA
- fasting
- stress (especially infection)
- intense exercise
- cholecystokinin
What inhibits glucagon secretion?
- glucose
- insulin
- somatostatin
Glucagon works through stimulation of what to mediate effects?
G-protein/cAMP
What are the effects of glucagon?
- increases glycogenolysis, gluconeogenesis, lipolysis, ketoacid formation
- little to no effect on glucose utilization by peripheral tissues
The action of glucagon are opposite the actions of what hormone?
insulin
What pathophysiology is associated with glucagon?
- glucagonoma
- hyperglucagonemia/diabetes mellitus associated with infection
In hyperglucagonemia, what happens to the ratio of glucagon:insulin?
it increases
What is the glucagonoma?
tumor of alpha cells in pancreas
What results from a glucagonoma?
results in diabetes mellitus and necrolytic migratory erythema
Somatostatin is stimulated by all nutrients, but inhibited by what?
insulin
What inhibits somatostatin?
- insulin and glucagon
- GI hormones
- GI motility, enzymes, gastric acid secretion
Somatostatin is secreted by what?
- delta cells of pancreas
- hypothalamus
- GI cells
How does adipose tissue act as an endocrine organ?
secretes hormones influencing feeding behavior, insulin sensitivity, glucose transport
What is the action of leptin secreted by adipose tissue?
- inhibits appetite by inhibiting neuropeptide Y
- increases BMR
What is the action of neuropeptide Y?
increase appetite
What is the action of adiponectin secreted by adipose tissue?
- improves insulin sensitivity
High adiponectin results in low risk of?
type II diabetes
Low adiponectin results in?
obesity and diabetes (cats)
What substances are secreted by adipose tissue?
- leptin
- tumor necrosis factor - alpha
- adiponectin
