Biochemistry

Question 1

what FBG is healthy

Answer 1

4-6mmol/L

Question 2

describe the structure of insulin

Answer 2

synthesised in rough ER as proinsulin
A&B chain connected by 2 disulphide bridges
cleaved to form insulin and C peptide

Question 3

describe how glucokinase dysfunction occurs within typ2 diabetes

Answer 3

higher blood glucose means cells lose ability to respond to glucose changes as it is outwith Km of glucokinase so sell is always producing maximal glucose

Question 4

describe biochemical secretion of insulin

Answer 4

glucose enters beta cell by GLU2 and phosphorylated to G-6-P by glucokinase
leads to mitochondrial metabolism to yield ATP
ATP inhibits Katp channel to cause cell to depolarise
causes Ca influx and fusion of secretory insulin vesicles to cell membrane and exocytosis

Question 5

what is the rough Km of glucokinase

Answer 5

5mmol/L

Question 6

why does insulin have a biphasic release

Answer 6

initial release is to prevent sharp hyperglycaemia and second phase is to bring blood glucose under control
second phase is slower and lesser concn

Question 7

explain how the insulin biphasic release is lost in T2DM

Answer 7

weakening and flattening of biphasic release, downregulated sensing process, mitochondrial exhaustion, run down insulin or glucokinase flux

Question 8

what part of the Katp channel do SUs bind to to cause closure in neonatal diabetes

Answer 8

SUR1

Question 9

besides blood glucose what does insulin also do

Answer 9

protein synthesis, glycogen synthesis, DNA synthesis, lipogenesis, growth response

Question 10

describe obesity linked insulin resistance

Answer 10

excess fat deposition in liver, muscle and pancreas leads to reduced insulin signalling so there is a deficit in adipose functionality

Question 11

what is Leprechauism-donohue syndrome

Answer 11

rare autosomal recessive defect in mutation in insulin receptor leading to severe resistance
growth retardation
absent s/c fat, decreased muscle mass and elfin face

Question 12

what is rabson mendelhall syndrome

Answer 12

rare autosomal recessive trait with mutaitons in insulin receptor reducing sensitivity
severe IR, hyperglycaemia, hyperinsulinaemia
acanthosis nigricans
fasting hypo due to hyperinsulinaemia and DKA

Question 13

describe ketone body formation

Answer 13

in lipolysis, fats are broken down to FFA and acetyl-CoA
FFA are used for energy but if, in starvation, oxaloacetate is used for gluconeogenesis then acetyl-CoA cannot be used for carb metabolism and is converted to ketone bodies

Question 14

describe the natural hx of T2DM

Answer 14

impaired glucose tolerance due to resistance leads to further increased insulin to control BG
more resistance occurs
beta cell dysfunction occurs and less insulin is produced

Question 15

risk factors for insulin resistance

Answer 15

overweight 
sedentary lifestyle 
hyperlipidaemia 
genes 
FHx
smoking 
high LDL and low HDL
hypertension 
heart disease 
high TAGs
polycystic ovarian syndrome

Question 16

describe how insulin resistance occurs in skeletal muscle

Answer 16

normal cells have insulin binding to IR and translocates GLUT4 to take up glucose
in abnormal cells then there is less tyrosine kinase activity so less downstream and failed GLUT4 recruitment for glycogenesis

Question 17

describe how insulin resistance can occur in adipose

Answer 17

obesity induced inflammation acts on gene expression pathways to increase inflammatory mediators
this causes inflammation that reduces glucose uptake to adiposite, liver

Question 18

describe the normal function of the liver in response to insulin

Answer 18

insulin promotes glycogenesis, lipid uptake in adipocyte or fatty acid oxidation balanced with carbohydrate metabolism

Question 19

describe pathway selective hepatic insulin resistance

Answer 19

less uptake of glucose and lesser glycogenesis
increased gluconeogenesis
increased lipolysis so more FFA to liver and more lipogenesis to create VLDL and fatty acid oxidation

Question 20

what is the gold standard for measurement of insulin sensitivity

Answer 20

hyperinsulinaemic-euglycaemic clamp

Question 21

describe the mechanism of the hyperinsulinaemic-euglycaemic clamp

Answer 21

2 catheters into jugular vein and carotid
keep arterial blood glucose euglycaemic
keep arterial insulin hyperinsulinaemic
in order to maintain this standard, more glucose needs infused
the more infused the more sensitive the patient is