Insulin & Glucagon Flashcards
What are the endocrine products of the following pancreatic cells:
- Alpha
- Beta
- Delta
- F
- Glucagon
- Insulin, c-peptide, proinsulin, amylin
- somatostatin
- pancreatic polypeptide
Blood supply to the pancreas comes from what sources?
Celiac trunk (splenic artery and anterior/posterior superior pancreaticoduodenal artery)
SMA (anterior/posterior inferior pancreaticoduodenal artery)
Where does blood leaving the pancreas drain into?
What are the implications of this?
Portal vein
Goes to liver and there is first pass effect where pancreatic hormones can be metabolized / inactivated
Discuss how blood enters the islets of langerhans.
Enters centrally –> insulin is delivered to alpha and delta cells –> can impact their function
True/false: somatostatin can regulate function of other cells within the islet of langerhans via gap and tight junctions.
True
What are the neural inputs to the pancreas?
SNS –> stimulate or inhibit
PSNS –> augment insulin secretion
Thought to mediate effects / response to sight/smell of food
Discuss the process of insulin production, processing and secretion.
Translated as preproinsulin –> goes to golgi –> cleaved into proinsulin –> secreted in vesicles –> cleaved to insulin + cpeptide in insulin granules
Which chromosome contains insulin gene?
Short arm of 11
True/false: more insulin is secreted than c-peptide.
False - equimolar amounts
What factors increase insulin secretion?
- High blood glu
- FFAs and AAs
- GIP, GLP-1, CCK, secretin, other incretins
- PSNS stimulation via Ach
- SNS stimulation via Beta adrenergic receptors
- Sulfonylureas
What factors have the opposite effect of insulin?
Glucagon, GH, cortisol
What factors decrease insulin secretion?
- Decreased blood glu
- Fasting
- Somatostatin
- Leptin
- SNS alpha adrenergic receptor activation
- Beta blockers
- Thiazide diuretics
Describe the process of how pancreatic beta cells sense glucose levels in the blood and then secrete insulin in response.
Pancreatic beta cells have GLUT2 transporters in their membranes, which are glucose leak channels. They are glucose independent, meaning these cells express constant levels of GLUT2 in their membranes regardless of glucose levels in the blood. The glucose enters the cell, undergoes glycolysis, TCA and OxPhos resulting in an increase in intracellular ATP. Increased intracellular ATP stimulates an ATP sensitive K+ channel which leads to closing of the channel and retention of K+ which depolarizes the cell. Cell membrane depolarization causes voltage dependent Ca++ channels to open, leading to an influx of Ca++, which is used to:
- promote transcription of genes related to insulin secretion
- promote insulin granule vesicle trafficking to the membrane for exocytosis and release
What part of the insulin secretion pathway do sulfonylureas act on?
They stimulate the ATP sensitive K+ channel causing the channel to remain closed and causing increased depolarization of the cell and increased insulin secretion
Discuss the structure and physiological role of proinsulin.
- Has very minor insulin-like activity, only really becomes an issue when a person has insulinoma b/c it can be produced in excess and trigger enough of a response that could result in hypoglycemia.
- Can complex with insulin –> again only really issue when hypersecreted
- Structure as shown in image
True/false: insulin’s quaternary structure consists of only 1 peptide
False - insulin has both an alpha and a beta chain that complex together into a quaternary structure
Insulin is released into portal blood in association with what ion?
Zinc
What happens to insulin once it binds to its receptor?
Internalized in vesicle, fused with endosome, proteolytically degraded