biochemistry

Question 1

what glucose level is hypoglycemia

Answer 1

<4mM

Question 2

what blood sugar level is considered high (risk of diabetes)

Answer 2

6-7mM

Question 3

what blood sugar is considered very high (diabetes)

Answer 3

> 7mM

Question 4

what do beta cells secrete

Answer 4

insulin

Question 5

what do alpha cells secrete

Answer 5

glucagon

Question 6

what do gamma cells secrete

Answer 6

somatostatin

Question 7

what do PP cells secrete

Answer 7

pancreatic polypeptide

Question 8

where is preporoinsulin synthesised

Answer 8

in the RER of pancreatic beta bells

Question 9

what happens after preproinsulin

Answer 9

cleaved to form proinsulin and a signal peptide which is then cleaved to form C peptide and insulin

Question 10

three chains of proinsulin

Answer 10

C peptide
A chain
B chain

Question 11

what is pure insulin then made up of

Answer 11

A chain and B chain

Question 12

5 types of synthetic insulin preparations

Answer 12

• ultra fast/ultra short acting
• short acting
• intermediate acting
• long acting
• ultra long acting

Question 13

what is the name of the ultra fast insulin

Answer 13

lispro

Question 14

when is lispro used

Answer 14

15 minutes of beginning a meal

-must be used in combination with long acting ones

Question 15

what is the most commonly used long-acting insulin

Answer 15

glargine

Question 16

when is glargine used

Answer 16

single bedtime dose

Question 17

what does glucose enter the beta cells through

Answer 17

the GLUT2 glucose transporter

Question 18

what is glucose phosphorylated by

Answer 18

glucokinase

Question 19

at what mmol/L of glucose does glucokinase start being more active

Answer 19

7

Question 20

what does an increased metabolism of glucose lead to in terms of ATP

Answer 20

leads to an increase in intracellular ATP concentration

Question 21

how many ATP is produced per glucose

Answer 21

36

Question 22

what does ATP then inhibit (in the secretion of insulin)

Answer 22

the ATP-sensitive K+ channel Katp

Question 23

what does inhibition of Katp lead to

Answer 23

depolarisation of the cell membrane

Question 24

what does depolarisation fo the cell membrane lead to in insulin secretion

Answer 24

opening of voltage-gated Ca2+ channels

Question 25

what does an increase in calcium concentration lead to

Answer 25

fusion of secretory vesicles with the cell membrane in release of insulin

Question 26

what happens in T1DM to the beta cells

Answer 26

they are mostly lost

Question 27

what does the first phase of insulin secretion prevent

Answer 27

a sharp increase in blood glucose

Question 28

what does the second phase of insulin secretion look like

Answer 28

broader and shorter

Question 29

why are there two phases

Answer 29

- 5% are immediately ready for release (RRP) | - reserve pool must undergo preparatory reactions to be ready to be released

Question 30

why in poorly controlled T2DM does insulin secretion weaken and flatten

Answer 30

- downregulation of the sensing process - limited glucokinase activity - mitochondrial exhaustion - reduced ATP production

Question 31

what is wrong in type 1 diabetes

Answer 31

destruction of pancreatic beta cells

Question 32

what is wrong in type 2 diabetes

Answer 32

hyperinsulinemia as the beta cells try to compensate for the hyperglycemia caused by insulin resistance

Question 33

later stages of type 2 diabetes, what can go wrong?

Answer 33

-decline in beta cell function

Question 34

what is associated with gestational diabetes

Answer 34

women with declining beta cell formation and high risk of future T2DM develops during pregnancy

Question 35

what is maturity onset diabetes of the young (MODY)?

Answer 35

monogenic disease with common clinical features to both type 1 and 2 -beta cell dysfunction but not autoimmune destruction

Question 36

what is neonatal diabetes

Answer 36

rare form of monogenic diabetes which is mainly caused by mutations in the glucose sensing mechanism

Question 37

what are the two proteins in the Katp channel

Answer 37

Kir6 | SUR1

Question 38

what can mutations in Kir6.2 lead to

Answer 38

neonatal diabetes | -as unable to secrete insulin

Question 39

what mutations can cause congenital hyperinsulinism

Answer 39

Kir6.2 and SUR1

Question 40

where do the mutations in MODY mostly happen

Answer 40

in glucokinase | -also several transcription factors (5)

Question 41

in which transcription factors are most of the MODY mutations

Answer 41

HNF 1 and 3

Question 42

what defines type 1 diabetes

Answer 42

loss of insulin secreting beta cells

Question 43

what defines MODY

Answer 43

defective glucose sensing in the pancreas and/or loss of insulin secretion

Question 44

what defines type 2 diabetes

Answer 44

initially hyperglycemia with hyperinsulinemia so primary problem is reduced insulin sensitivity in tissues

Question 45

what does insulin regulate

Answer 45

- amino acid uptake in muscle - DNA synthesis - protein synthesis - growth responses - glucose uptake in muscle and adipose tissue - lipogenesis in adipose tissue and liver - glycogen synthesis in liver and muscle - gene expression - turns off lipolysis and gluconeogenesis in liver

Question 46

how can obesity cause insulin resistance

Answer 46

due to excess fat deposition in liver, muscle and pancreas, reducing insulin signalling in those tissues, combined with a deficit in adipose functionality

Question 47

symptoms of diabetic ketoacidosis

Answer 47

- vomiting - dehydration - increased heart rate - distinctive smell on breath

Question 48

where are ketone bodies formed

Answer 48

liver mitochondria

Question 49

how does insulin usually reduce the risk of ketone body overload

Answer 49

by inhibiting lipolysis

Question 50

when is DKA a risk in T1DM

Answer 50

if insulin supplementation is missed and hyerglycemia ensues

Question 51

what results in fatty acid oxidation in relation to insulin

Answer 51

having no insulin reduces the amount of glucose being taken up by tissues from blood and reduces glycolysis making the body switch to fatty acid oxidation

Question 52

what causes ketones to be produced as a result of fat utilisation

Answer 52

- fat utilisation outstrips glucose utilisation - no glycolysis - pyruvate/oxaloacetate is limited - acetly CoA is diverted to ketones

Question 53

what can cause ketosis

Answer 53

- starvation | - diabetes