Exam #4: Endocrine Physiology Flashcards
What are the cell types found in the pancreatic islets?
Alpha Beta Delta Epsilon PP of F
What hormones are secreted by the alpha cells of the pancreatic islets?
glucagon
proglucagon
What hormones are secreted by the beta cells of the pancreatic islets?
Insulin Proinsulin C-peptide IAPP GABA
What hormones are secreted by the delta cells of the pancreatic islets?
Somatostatin, negative regulator of insulin secretion
What hormones are secreted by the epsilon cells of the pancreatic islets?
Ghrelin
What hormones are secreted by the F cells of the pancreatic islets?
Pancreatic polypeptide
What are the biosythetic steps of insulin?
1) Insulin gene translated to preproinsulin in ER
2) Preproinsulin is cleaved immediately
3) Proinsulin is packaged into secretory vesicles
4) Conversion of proinsulin to insulin and C-peptide in the secretory vesicles
*Thus, C-peptide and insulin are secreted together. C-peptide is an emerging area of research & a marker of insulin secretion.
What is the half-life of insulin?
3-5 min because it circulates in a unbound form, which gives it a short half-life
What are the stimulators of insulin? Outline the mechanisms of insulin secretion by these stimulators.
Glucose= most potent stimulator of insulin release
- Glucose moves down its concentration gradient into the pancreatic beta cell; this increase in intracellular glucose leads to an increase in ATP/ ADP ratio
- Increased ATP/ADP ratio leads to closing of a K+ channel
- Beta cell membrane leads to DEPOLARIZATION b/c of the accumulation of K+ (positive charge) on the inside of the cell
- Sensed by a voltage-gated Ca++ channel
- Ca++ rushes in
- Insulin vesicles are exocytosed
Vagal stimulation
- ACh activates muscarininc 3 receptors
- Gq
- PLC
- Intracellular Ca++ increase leads to vesicular docking and insulin release
What are the amplifiers of insulin?
Hormones
- Glucagon like peptide (GLP1)*****
- Gastric inhibitory peptide (GIP)
- Cholecystokinin (CKK)
- Gastrin
- Secretin
Catecholamines
- B-adrenergic stimulation i.e. an epinephrine surge
What are the inhibitors of insulin?
Hormones
- Somatostatin
Catecholamines
- alpha-adrenergic stimulation
- SNS
What are the cellular events that occur following activation of the insulin receptor?
1) Insulin binds to the insulin receptor
2) Activation of large number of intracellular molecules
3) Promotion of GLUT4 transporters insertion into the membrane so glucose can flow down its concentration gradient into the cell
Insulin receptors regulate mitogenic and metabolic processes
What tissues utilize glucose transporters for the cellular uptake of glucose?
GLUT4 is the glucose transporter that is regulated by insulin, the other transporters ARE NOT
- Skeletal muscle
- Adipose tissue
What are the metabolic consequences of insulin in the liver?
1) Promotion of anabolism
- Glycogen synthesis & storage
- Inhibition of glycogen breakdown
- Increased protein synthesis
- Increased triglyceride synthesis
2) Inhibition of catabolism
- Inhibit glyocogenolysis
- Inhibit ketogenesis (fat to FFA)
- Inhibit gluconeogenesis
*Generally, you’re promoting the formation of bigger molecules and the breakdown of bigger molecules into smaller ones
What are the metabolic consequences of insulin in the adipose tissue?
Increased triglyceride storage by:
- Promoting FFA uptake
- Promoting esterification of FFA
- Inhibition of lipolysis
What are the metabolic consequences of insulin in the skeletal muscle?
1) Increased protein synthesis by increasing amino acid uptake
2) Increased glycogen synthesis
- Increased glucose uptake by GLUT4
- Increased glycogen synthase activity
- Inhibition of glycogen phosphorylase
What is glucagon? What are the general effects of glucagon binding to the glucogon receptor?
- Peptide hormone that is produced by the alpha cells of the pancreas & endocrine cells of the gut; has an opposite effect of insulin
- Binds a GPRC that eventually promotes glucose output and ketone body output
Remember, insulin= energy storage, glucagon= energy mobilization
What are the regulators of glucagon secretion?
1) Glucose inhibits glucagon secretion–the precise mechanism is unclear
2) Catecholamines and GI hormones promote glucagon release
3) PNS & SNS stimulation can promote glucagaon release
4) Fatty acids suppress glucagon
Compare the impact of glucagon & insulin on gluconeogenesis.
Insulin= decreases/ inhibits gluconeogenesis
Glucagon= increases or stimulates gluconeogenesis
Compare the impact of glucagon & insulin on glycogenesis/ glycogenolysis.
Insulin= promotes glyocogenesis i.e. formation of glycogen
Glucagon= promotes glycogenolysis i.e.breakdown of glycogen
Compare the impact of glucagon & insulin on glycolysis.
Insulin= increases glycolysis
Glucagon= decreases glycolysis
Compare the impact of glucagon & insulin on ketogenesis.
Low insulin & high glucagon= formation of ketone bodies i.e. ketogenesis
How do insulin and glucagon effect blood glucose levels?
Glucagon= raise
Insulin= lower
What are GLPs?
Glucagon-like peptides
What is the function of GLP1?
- Secreted in response to glucose, lipids, and PNS
- Promotes BOTH insulin and somatostatin secretion
- Protects and promotes growth of B-cells
What is dipeptidyl peptidase 4 (DPP-4)?
Enzyme that degrades GLP1
What is IAPP & what is the function of IAPP?
- Islet amyloid polypeptide that is produced by B-cells
- Secreted by stimuli that increase insulin secretion
- Decreases glucagon secretion & inhibits GI motility/ gastric emptying
What is Pancreatic Polypeptide, & what is the function of Pancreatic Polypeptide?
- Produced and secreted by F cells
- Neuronal control
- Regulates EXOCRINE function of the GI tract i.e. gallbladder contraction, gastric acid secretion, and GI motility
What is Somatostatin & what is the function of Somatostatin?
- Produced by delta cells
- Inhibits insulin secretion in a paracrine fashion through activation of SSTR-5
What is Ghrelin & what is the function of Ghrelin?
- Produced by epsilon cells
- Induces gastric emptying, promotes acid secretion, and increases appetite
