Lecture 8+9+DLA

Question 1

synthesis of insulin?

Answer 1

1. mRNA is produced and translation happens
2. formation of N-terminal signal sequence doing translation that allows movement to RER
3. N-terminal sequence penetrates RER and is now preproinsulin
4. signal sequence is cleaved; now proinsulin
5. proinsulin moves from RER to Golgi, where it is cleaved, thus forming insulin and C-protein
6. insulin and C-protein are put into vesicles and excreted from cell

Question 2

purpose of the C-protein?

Answer 2

enables correct disulfide bonding

3

Question 3

insulin in the blood?

Answer 3

ends up forming hexamers with zinc in the center

will separate in monomers to bind to insulin receptor

Question 4

C- peptide test?

Answer 4

C-protein has a longer half-life compared to insulin

represents endogenous insulin synthesis

Question 5

what is the role of A,B,D, and F cells in the islets of Langerhans?

Answer 5

Alpha: glucagon release

Beta: insulin release

Delta: somatostatin release; decrease glucagon and insulin release (paracrine)

F-cells: release pancreatic polypeptide hormone

Question 6

Activating the secretion of insulin?
major and minor activators?
inhibit?

Answer 6

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

Question 7

Insulin effects on skeletal muscle?

Answer 7

glucose uptake from the blood via GLUT-4

increased Na/K ATPase synthesis

increased AA uptake; increased muscle protein synthesis

Question 8

Insulin effects on adipose tissue?

Answer 8

uptake of FA and glucose that results in TAG synthesis

glucose uptake by GLUT-4

Question 9

regulation of glucagon?
activating?
inhibiting?

Answer 9

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

Question 10

where are glucagon receptors found?

Answer 10

hepatocytes and renal cortex cells

Question 11

what hormones are used to prevent hypoglycemia?

Answer 11

glucagon, epinephrine, cortisol, and growth hormone

Question 12

what and when do adrenergic / neuroglycopenia symptoms begin?

Answer 12

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)

Question 13

normal glucose levels?

what is hypoglycemia?

Answer 13

blood glucose lower than 55 mg/dL is hypoglycemia

normal: 70-110 mg/dL

Question 14

treatments for those with hypoglycemia?

conscious and unconscious?

Answer 14

conscious: oral consumption of glucose
unconscious: injection of glucagon or epinephrine to activate hepatic glycogen degradation

Question 15

what can lead to hypoglycemia?

Answer 15

1 .insulin injection

2. reactive postprandial
3. hereditary diseases
4. high alcohol intake

Question 16

alcohol-related hypoglycemia?

Answer 16

ethanol leads to high levels of NADH/ NAD, thus the reduction of gluconeogenesis

Question 17

Insulinoma?

Answer 17

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

Question 18

Factitious hypoglycemia

Answer 18

can be found in patients who stimulate a disease or artificially induce clinical symptoms

can be done by insulin injection and sulfonylurea

Question 19

factitious hypoglycemia
blood levels when insulin is injected
blood levels when sulfonylurea

Answer 19

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

Question 20

how pH alters plasma Ca?

Answer 20

alkalosis leads to higher Ca binding
thus decreased plasma Ca

acidic pH leads to less Ca binding
thus increased plasma Ca

Question 21

diseases that decrease blood Ca?

increase blood Ca ?

Answer 21

nephrotic syndrome, malnutrition, and liver disease

multiple myeloma (increase)

Question 22

mechanism of PTH suppression?

Answer 22

increased ionized calcium binds to the Ca-R

increases DAG, IP3, and Ca
increased PLC

thus inhibition of PTH

Question 23

action of PTH on bone?

Answer 23

increase IP3 and cAMP

increase M-CSF, RANK, and IL-6

increase bone resorption

Question 24

Cutaneous synthesis of Vit D

Answer 24

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)

Question 25

action of Vit D in the intestine?

Answer 25

low intracellular Ca levels

increased Ca and PO4 reabsorption

Question 26

hypocalcemia

Answer 26

increases membrane excitability

paresthesia
hypocalcaemic tetany

will see Chvostek’s sign and trousseau’s sign

EKG will have a prolonged QT interval

Question 27

hypercalcemia?

Answer 27

nephrogenic DI (polyurea and polydipsia)
peptic ulcer disease
kidney stones (urolithiasis)
neurological and psychiatric symptoms

EKG will have a shortened QT interval

Question 28

Primary hyper-parathyroidism

causes? symptoms?

Answer 28

usually due to parathyroid tumor
ectopic parathyroid tissue

excess PTH causes: 
increase serum Ca 
phosphaturia, polyurea, and calcinuria
kidney stones 
peptic ulcer disease 
cystic lesion on bone

Question 29

secondary hyper-parathyroidism

Answer 29

due to Vit D deficiency
poor absorption of fat
inability to make D3
increased need for Ca during pregnancy

increased PTH
low Ca and low Ca in urine
low PO4 levels
increased PO4 in urine

Question 30

Primary hypo-parathyroidism

Answer 30

cause: could be due to accidental removal or radiation

low Ca and high PO4 plasma levels
tetany
prolonged QT interval