Endocrinology- glucose homeostasis

Question 1

How is glucose regulated?

Which hormones increase or decrease it?

Answer 1

Increase Glucagon cortisol, GH, catecholamines

decrease insulin

Question 2

What happens when insulin function doesn’t happen?

What is conditon called?

Answer 2

blood glucose can’t be decreased, hyperglycaemia

diabetes mellitus

Question 3

What is a retroperitonael structure?

give an example of one?

Answer 3

anatomical spac behind (retro) the peritoneum (abdonminals)

pancreas

Question 4

1. What are the majority of cells in the pancrease? What do they produce?
2. What are the clumps cells called that aren’t the majority? What do they do?

Answer 4

1. Exocrine acinar cells, secretion e.g enzymes to small intestine
2. islets of langerhans, glucose regulation

Question 5

Labell histology of Islets of Langerhans

Answer 5

Question 6

What type of junctions are between islets cells?

What do they allow

Answer 6

Gap junction- small molecules pass between cells

Tights - small intercellular spaces

Allows for paracrine communcations

Question 7

What is function of pancreatic hormones?

Answer 7

Insulin- growth/developments and reduce glucose

glucagon - increase blood glucose

somatostatin- keep both hormones in check, negative feedback

Question 8

What system feedback to beta cells when blood glucose is increased?

Answer 8

negative feedback from somatostatin

glucagon produced to ensure don’t overshoot

other meal components, AA and GI hormones from digestion- stimulation effect of b cells

PNS- ‘rest and digestion’

Question 9

overall what does insulin do?

Answer 9

increase uptake of glucose into cells via GLUT4 in adipose tissue and skeletal muscles

build up glucagon stores, protien synthsis, lipogensis in liver

breakdown of glucose

reduction tranport aminao acids and fat breakdown

Question 10

What systems feedback to alpha cells when blood glucose is decreased?

Answer 10

insulin is switched off, no longer produced

somatostatin- counterregulator negative feedback

some amino acids and GI hormones- so when after meal and insulin released don’t overshoot so glucagon also produced

Question 11

What effects do glucagon have on general metabolism?

Answer 11

increase blood glucose

increase aminao acid transport to liver and lipolysis for glucogenesis

increase hepatic (liver) glycogenolysis

Question 12

What happens after pro longed excercise e.g 5000m run?

Answer 12

glucagon regulated reponse i.e previous flashcard

Question 13

How do B cells know how to secrete insulin?

Answer 13

GLUT2 transporter not insulin sensitive, allows full movement of glucose inside B cells

glucose —-> G6P using Glucokinase, continual production

and makes ATP

closes K+ gated channels, remains intracelluar

leads to depolarisation + Ca2+ influx lead to release pre formed insulin vesicles

Ca2+ also causes the synthesis of new insulin.

Question 14

Difference between glucokinase (hexokinase 1V) and normal hexokinase in kidney?

Answer 14

Not subject to negative feedback

G6P does not inhibit it, so continually conversion to G6P

Question 15

What is special about GLUT2 transporter?

Answer 15

Not insulin sensitive, high affinity to glucose.

allows intracellular conc to mirror conc of bloodstream.

So synthesizes insulin in accordance of intracel conc,

not all or nothing.

Question 16

How in insulin molecular synthesized? (precurer molecule?)

Answer 16

Stored as pre insulin (insulin and C peptide)

then proteolytic cleavage

to produce 1:1 C peptide and insulin in blood

Question 17

What is signficance of C peptide?

Answer 17

Measure it gives accurate indication of insulin levels

insulin is unstable molecules

Question 18

What incretin GI effect?

What is it due to?

Answer 18

oral goes through digesitive system,

gut hormones enhancing insulin secretion (stimulating it more)

focally GLP-1

Question 19

What is the main GI hormone in incretin effect?

When and what cells is it secreted?

What is it effects on feelings?

Answer 19

Glucagon like peptide-1

secreted due to nutrients in guts,

product of pro-glucagon gene by L cell in colon

stimulates insulin and supress gluacgon

feeling fullness satiety increase

short half life- degraded by enzyme DPPG-4

DPPG-4 inhbitor used as treatment for diabities feeling of fullness help with obesity

Question 20

What is first phase insulin release?

Effect of type 2 diabities?

Answer 20

whole system if affected. beta cells work hard for so long unable to produce more insulin

Question 21

How does insulin bind to cells?

What intracelluar affects does it to have?

Answer 21

Binds to a-subunit (extracellular) domain of insulin recepotor

confortation change of tyrosine kinase domains of B subunit

GLU4 from intraceullar expressed on CM- allow uptake of glucose