Hormones of the Pancreas Flashcards
What are 2 major hormones produced in the pancreas and what is their effect on glucose?
insulin - decrease Glc
glucagon - increase Glc
what is a normal glucose range?
5-6mM
what other 3 hormones affect Glc and how do they affect it?
cortisol - increases Glc
epinephrine - increases Glc
Growth hormone - increases Glc
what are the endocrine cells of the pancreas? exocrine cells?
endo - islets of langerhans
exo - acini
what are the 4 major cell types of the islet of Langerhans and what hormones do they produce?
A(alpha) - glucagon
B(beta) - insulin
D(delta) - somatostatin
F - pancreatic peptide
What is proinsulin?
Uncut insulin, consisting of A + B + C chains with little biologic activity
What is mature insulin? What is the piece cut off and what is its function?
mature insulin = A + B chain
C peptide cut off - no known function
what is the cleaving enzyme of proinsulin?
proprotein convertase
What occurs after cleavage of proinsulin?
post translational processing occurs in Golgi and secretory granules
Mature insulin complexed with zinc and C peptide released from G granules by exocytosis is regulated
What do stimulants of insulin release? (4pts)
sugars (Glc, mannose)
AAs (leucine)
Vagus nerve stimulation
sulfonylureas
What are molecules that amplify glucose?
enteric hormones (gastrin, secretin, cholecystokinin) Neural amplifiers (beta adrenergic effect of catecholamines) AAs (arginine)
what are two inhibitors of insulin release?
neural: alpha-adrenergic effect of catecholamines
humoral: somatostatin
How does food influence Glc, glucagn, and insulin levels?
Glc goes up first, then insulin
~1hr after meal is peak
Glucagon opposite of Glc (lowest ~1hr after meal)
Where are the 4 areas of the body that Glc can be utilized?
Brain
Muscle
Adipose tissue
liver
what is Glc converted to in the muscle?
glycogen and protein (also AA)
what is Glc converted to in adipose tissue?
triglycerides and FAs
what is Glc converted to in the liver?
glycogen and then stored
What effect does insulin have on the body?
Glc uptake into cells
glycogen synthesis
lipid synthesis
protein synthesis by increased AA uptake
is insulin anabolic or catabolic?
anabolic
How is Glc taken up into cells?
by facilitated diffusion using glucotransporters GLUT1-5
What is GLUT1?
brain endothelium (not sensitive to insulin)
what is GLUT2?
release glc from cells (livers, fat, muscle)
what is GLUT3?
neurons (not sensitive to insulin)
what is GLUT4?
very sensitive to insulin in uptaking Glc into cells
what is GLUT5?
uptake of ingested Glc in gut
In what parts of Glc metabolism does insulin increase activity? (7pts)
1) Glc to Glc-6-P
2) Glc-6-P to glycogen
3) Fru-6-P to Fru-1,6-bisP
4) Pyruvate to AAs
5) AAs to proteins
6) Pyruvate to AcCoA
7) AcCoA to Lipids
In what parts of Glc metabolism does insulin decrease activity? (3pts)
1) Fru-1,6-bisP to fructose
2) Pyruvate to OAA
3) OAA to PEP
What is the function of glucagon?
stimulates gluconeogenesis and lipolysis (incr. glycerol untilization and decr. triglyceride synthesis)
potent releaser of Glc
Describe the carbohydrate metabolism in the muscles.
Glycogen breakdown to Glc in muscles is unaffected by glucagon but glucocorticoids are effective
Lactate from muscles travels in blood to liver where it is used to make Glc that is sent to other tissues
Describe lipid metabolism.
Affected by glucagon.
triglyceride is converted to glycerol (used to make Glc) and FAs
FAs make AcCoA, that convert to Ketone bodies (energy source)
what causes diabetes mellitus (DM)?
insulin deficiency and/or a reduction in effectiveness of insulin
what is diabetes mellitus?
a syndrome of disordered metabolism with inappropriate hyperglycemia
what are the two forms of DM? which is more common?
Type 1 - destruction of beta cells (low or absent insulin)
type 2 - metabolic syndrome (more common)
what are the two kinds of T2DM?
obese T2DM
non-obese T2DM
what is obese T2DM?
insulin resistance (decreased sensitivity to insulin due to receptor and post receptor defects) often with hyperplasia of beta cells and beta cells are insensitive to Glc
what is non-obese T2DM?
strong genetic trait
often associated with mutations in insulin, insulin receptors and/or signal transduction molecules
how does decreased glc uptake affect the body?
leads to hyperglycemia, glycosuria, and osmotic diuresis
this causes dehydration and loss of electrolates which can lead to CV depression and ultimately shock, coma, or death
why does glc toxicity occur from chronic hyperglycemia?
oxidative stress due to increase in oxygen radicals and alterations to protein glycosylation and functions
what are the 4 categories of complications caused by DM?
ophthalmologic complications
neurological problems
cardiovascular defects
renal complications
what kind of ophthalmologic complications could arise due to DM?
diabetic retinopathy
cataracts
what kind of renal complications could arise due to DM?
diabetic nephropathy
infections
what kind of neurological problems could arise due to DM?
diabetic neuropathy (sensory, motor, autonomic)
what kind of cardiovascular defects could arise due to DM?
cardiomyopathy
myocardial infarction
what is the primary treatment for T1DM?
insulin
nature of dietary intake
what is the primary treatment for T2DM?
nutritional therapy, wt loss (diet and exercise)
What are some medications that could help treat DM?
Metformin (Biguanides)
Glyburide (Sulfonylureas)
Rosiglitazone (Thiazolidinediones)
Acarbose (Glucosidase inhibitors)
how does metformin help treat DM?
inhibits gluconeogenesis
how does Glyburide help treat DM?
insulin secretagogues (secretes insulin)
how does Rosiglitazone help treat DM?
increase sensitivity to insulin
how does Acarbose help treat DM?
decrease sugar availability (inhibit digestion of complex carbs)
