Lecture 8+9+DLA Flashcards
synthesis of insulin?
- mRNA is produced and translation happens
- formation of N-terminal signal sequence doing translation that allows movement to RER
- N-terminal sequence penetrates RER and is now preproinsulin
- signal sequence is cleaved; now proinsulin
- proinsulin moves from RER to Golgi, where it is cleaved, thus forming insulin and C-protein
- insulin and C-protein are put into vesicles and excreted from cell
purpose of the C-protein?
enables correct disulfide bonding
3
insulin in the blood?
ends up forming hexamers with zinc in the center
will separate in monomers to bind to insulin receptor
C- peptide test?
C-protein has a longer half-life compared to insulin
represents endogenous insulin synthesis
what is the role of A,B,D, and F cells in the islets of Langerhans?
Alpha: glucagon release
Beta: insulin release
Delta: somatostatin release; decrease glucagon and insulin release (paracrine)
F-cells: release pancreatic polypeptide hormone
Activating the secretion of insulin?
major and minor activators?
inhibit?
major activator: elevated blood glucose
enhancement of glucose-induced release:
AA: Arg, Leu, and Glu
Gut hormones: GLP-1 and GIP
neural input: parasympathetic stimulation after a meal (ACh)
Inhibits insulin release:
epinephrine and norepinephrine
somatostatin
Insulin effects on skeletal muscle?
glucose uptake from the blood via GLUT-4
increased Na/K ATPase synthesis
increased AA uptake; increased muscle protein synthesis
Insulin effects on adipose tissue?
uptake of FA and glucose that results in TAG synthesis
glucose uptake by GLUT-4
regulation of glucagon?
activating?
inhibiting?
activating:
Low blood glucose
AA: Arg, Ala, and other AA
epinephrine and norepinephrine
cortisol
neural input: sympathetic stimulation during stress
inhibiting:
increased blood glucose
insulin
somatostatin
where are glucagon receptors found?
hepatocytes and renal cortex cells
what hormones are used to prevent hypoglycemia?
glucagon, epinephrine, cortisol, and growth hormone
what and when do adrenergic / neuroglycopenia symptoms begin?
less than 55 mg /dL symptoms begin
adrenergic: anxiety, palpation, tremors, sweating
occurs due to epinephrine release
neuroglycopenia: headache, confusion, slurred speech, coma, and death (below 40 mg/dL)
normal glucose levels?
what is hypoglycemia?
blood glucose lower than 55 mg/dL is hypoglycemia
normal: 70-110 mg/dL
treatments for those with hypoglycemia?
conscious and unconscious?
conscious: oral consumption of glucose
unconscious: injection of glucagon or epinephrine to activate hepatic glycogen degradation
what can lead to hypoglycemia?
1 .insulin injection
- reactive postprandial
- hereditary diseases
- high alcohol intake
alcohol-related hypoglycemia?
ethanol leads to high levels of NADH/ NAD, thus the reduction of gluconeogenesis
Insulinoma?
is a tumor of the pancreatic islet cells that releases insulin
severe hypoglycemia can result due to rapid uptake of glucose
abnormally high levels of insulin blocks the action of the insulin counter-regulatory hormones
the blood will have high levels of insulin, C peptide, and proinsulin
Factitious hypoglycemia
can be found in patients who stimulate a disease or artificially induce clinical symptoms
can be done by insulin injection and sulfonylurea
factitious hypoglycemia
blood levels when insulin is injected
blood levels when sulfonylurea
injection of insulin: high insulin low C-peptide low to no proinsulin no sulfonylurea
oral sulfonylurea: high insulin high C-peptide present proinsulin sulfonylurea will be present
how pH alters plasma Ca?
alkalosis leads to higher Ca binding
thus decreased plasma Ca
acidic pH leads to less Ca binding
thus increased plasma Ca
diseases that decrease blood Ca?
increase blood Ca ?
nephrotic syndrome, malnutrition, and liver disease
multiple myeloma (increase)
mechanism of PTH suppression?
increased ionized calcium binds to the Ca-R
increases DAG, IP3, and Ca
increased PLC
thus inhibition of PTH
action of PTH on bone?
increase IP3 and cAMP
increase M-CSF, RANK, and IL-6
increase bone resorption
Cutaneous synthesis of Vit D
7- dehydrocholesterol
UV light
cholecalciferol (can be from diet)
25-hydroxylase
25- hydroxycholecalciferol (in liver)
1- hydroxylase with PTH
1,25 OH cholecalciferol (happens in kidney)
