Endocrine Physiology I Flashcards
Insulin, Glucagon, and Diabetes/Hypothalamic-Pituitary Axis
What are the two functions of the pancreatic cells?
- Make enzymes
- Make hormones (Endocrine)
What are the main function of Acini (cluster of cells)?
Make enzymes that dump into the duodenum via pancreatic duct
Where are the majority of hormones created in the pancreatic cells?
Islet of Langerhans
-Glucagon, insulin, and somatostatin
In the pancreas, what do alpha cells (20%) make?
Glucagon
In the pancreas, what do beta cells (70%) make?
Insulin
In the pancreas, what do δ cells (10%) make?
Somatostatin
What is the function of somatostatin?
Inhibits Insulin, Glucagon and GH
What is the normal range of glucose (mg/dl)?
~80-100 mg/dL
How does insulin and glucagon balance each other?
What effect does amino acids have on glucagon and insulin?
Same, slightly positive effect
What has the greatest effect on the release of insulin?
Hyperglycemia
What has the second greatest effect on insulin release?
Incretins (GIP/GLP)
What has a moderate postive effect on insulin release? (2)
Glucagon, Sulfonylurea drugs
What has an inhibitory effect on insulin? (3)
NE/Epi & Cortisol, Somatostatin, Fasting/excersize
What has the greatest effect of the release of glucagon? (1)
Hypoglycemia
What has a moderate positive effect on the release of glucagon? (3)
Amino acids, NE/Epi & Cortisol, Excersize/fasting
What has a moderete negative effect on the release of glucagon? (3)
Incretins (GIP/GLP), Insulin, Somatostatin
What do sulfonylurea drugs do? (3)
They stimulate insulin release
- Treat T2D
- Block B-Cell KATP
B-Cells release what? (2)
Insulin and C-peptide (Connecting-peptide)
What do incretins do?
Incretins stimulate the B-cells and inhibit the alpha cells to increase insulin and lower glucagon.
What does the enzyme dipeptidyl pedptidase-4 (DPP4) do?
Inactivate GLP-1 and GIP
What do antagonists of DPP-4 do?
Antagonists of DPP-4 improve endogenous insulin secretion!
Is insulin release higher when glucose is given orally or through IV?
Orally
What function does insulin have on glucose and AA uptake in skeletal muscle?
Anabolic
- Increases glucose and AA uptake in skeletal muscle
- Supresses hepatic glucose production
- Inhibits lipolysis
What effect does glucagon have in liver, adipocytes and skeletal muscle? (4)
Catabolic
- Increases hepatic glycogenolysis
- Increeases hepatic gluconeogenesis
- Increases hepatic ketone formation
- Stimulates lipolysis
What is the largest storage site of glucose, and the tissue responsible for T2D?
Skeletal muscle
What receptor does insulin act on in myocytes/adipocytes?
GLUT4
What pathway mediates most of insulin’s metabolic effects? The phosphorylation of what proteins mediates this pathway?
Akt pathway
IRS-1, Akt, PKCz, AS160
What is insulitis?
What is the cause of type 1 diabetes?
Loss of beta cells by autoimmune destruction, usually genetic and triggered from environmental factors. This ultimately leads to low insulin levels and decreased glucose uptake that leads to hyperglycemia
In T1D, as beta cell mass decreases, what happens to insulin release over time?
What leads to the development of type 2 diabetes (T2D)?
Insulin resistance from inactivity and genetics precedes obesity.
Obesity leads to B-cell hyperplasia where glucose is normal and insulin is elevated.
In early B-cell fatigue, glucose and insulin are elevated.
In late B-cell failure, glucose is elevated and insulin is decreased.
What causes insulin resistance?
Excess glucose intake leads to oxidative stress where a JNK protein phosphorylates a serine residue on IRS-1, inactivating the Akt pathway that normally brings GLUT4 receptors to the membrane to uptake glucose
If you wanted to transport glucose at the same rate of an insulin sensitive person, and you were insulin resistant how would you achieve normoglycemia?
You would have to produce more insulin, which is what happens in early stages of type 2 diabetes
What effect does T2D’s have on endogenous glucose production and glucose disposal rate? (2)
Preoperative elevated HBA1C is a predictor of what?
What clinical implications does diabetes have regarding anesthesic management?
Low insulin/glucagon can lead too? (Primarily in T1D)
Ketogenesis, elevated sugar, dehydration, and coma
What is the best clinical indicator that a patient has insulin resistance?
Obesity
High fructose corn syrup ultimately leads to increase of?
VLDL
What functions as a glucose sensor in the process of insulin release?
Pancreatic B-cell
The IRS-PI3K pathway is essential for glucose uptake by ________ and _________?
insulin and exercise
What are the principle metabolic effects of insulin? (3)
- Increase glucose utilization in skeletal muscle
- Supress hepatic glucose production
- Inhibit lipolysis
What do incretins do?
Amplify glucose-induced insulin release
How does glucagon antagonize insulin’s effects?
Stimulating hepatic glucose release
What does a disruption in the balance of insulin and glucagon lead too? (2)
- Ketogenesis
- Hyperosmolar coma
T or F. Your body metabolizes fructose much differently than glucose?
True
What is the main function of the hypothalamus?
What is the main function of the pituitary?
Where are the magnocellular neurons located in the pituitary? What are there function?
Posterior
Produces OT, AVP and stores
Where are the parvicellular neurons stored? What are their function?
Anterior
Produces releasing/inhibiting hormones
What are the neurohormones (releasing hormones)?
What are the tropic hormones?
What are the non-tropic hormones?
How is GH (Somatotropin) release regulated?
What are the normal biological actions of GH-IGF-1?
Decrease glucose uptake
Increase lipolysis
Increase hepatic gluconeogenesis
Decrease skeletal muscle glucose uptake
Increase lean body mass
Increase organ size
Increase linear growth
Why is GH release pulsatile, rather than sustained?
Why is GH surge at night significant?
Growth and repair during rest
What effect would a high carbohydrate meal before bed have?
How does thyroid hormone, growth hormone, androgens and estrogens vary over time in a normal person?
What are the net effects of GH/IGF-1 on growth?
What disease is GH overexpression before puberty?
What disease is GH deficiency before puberty?
What is achondroplasia?
Mutation in gene 3 (FGFR3); not related to GH
What is acromegaly?
GH overexpression that starts at puberty and sustains through adulthood
What is Laron’s syndrome?
GHR insensitivity; no IGF1
