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Endocrinology > Biochemistry of Insulin > Flashcards

Biochemistry of Insulin Flashcards

1
Q

Which cells secrete insulin?

A

b-cells

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2
Q

Which cells secrete glucagon?

A

alpha cells

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3
Q

Which cells secrete somatostatin?

A

d cells

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4
Q

Which cells secrete pancreatic polypeptide?

A

PP cells

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5
Q

Where is insulin made?

A

RER in b cells of pancreas

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6
Q

What is insulin synthesized as?

A

larger single chain preprohormone called preproinsulin

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7
Q

What chains does insulin contain?

A

2 polypeptide chains, linked by disulphide bonds

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8
Q

Why is human insulin now used?

A

to avoid problem of antibody formation

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9
Q

What is the glucose sensor which leads to insulin secretion?

A

Glucokinase

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10
Q

How does glucose enter b cells?

A

through GLUT2 glucose transporter

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11
Q

What phosphorylyses glucose?

A

glucokinase

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12
Q

What does a change in glucose concentration lead to?

A

dramatic change in glucokinase activity

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13
Q

Increased metabolism of glucose leads to what happening to intracellular ATP?

A

increases

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14
Q

What does ATP do to the KATP channel?

A

inhibits this

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15
Q

What does inhibition of KATP lead to?

A

depolarisation of cell membrane

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16
Q

What does depolarisation of cell membrane result in opening of?

A

calcium channels

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17
Q

How does an increases in calcium concentration in the cells cause insulin release?

A

leads to fusion of secretory vesicles

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18
Q

What is release of insulin in terms of phases?

A

biphasic

19
Q

Why are there two phases of insulin?

A

5% of insulin granules immediately ready for release

Reserve pool must undergo preparatory reactions to become mobilised and available for release

20
Q

Which proteins do KATP channels consist of?

A

KIR6.1 (inward rectifier subunit, pore)

SUR1 (sulphonylurea receptor, regulatory)

21
Q

What type of structure is the KATP channel

A

octomeric

22
Q

Are both proteins (KIR6.1 and SUR1) required for a functional channel to form?

A

YES BOTH

23
Q

Which class of drugs directly inhibits KATP?

A

sulphonylureas eg glibenclamide, tolbutamide

24
Q

What is KATP stimulated by?

A

diazoxide

25
Q

What does diazoxide do to insulin secretion?

A

inhibits

26
Q

What causes MODY?

A

mutations - genetic defect in b cell function

27
Q

What type of diabetes is MODY?

A

familial version of Type II

28
Q

What do HNF transcription factors and MODY play a key role in?

A

pancreas foetal development and neogenesis

regulate beta cell differentiation and function

29
Q

What allows for differentiation between type 1 diabetes and MODY?

A

robust genetic screening - means MODY can be treated with sulphonylurea rather than insulin

30
Q

loss of insulin secreting beta cells?

A

type 1 diabetes

31
Q

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

A

MODY

32
Q

Initially hyperglycaemia, with hyperinsulinaemia, so primary problem is reduced sensitivity in tissues?

A

Type 2 diabetes

33
Q

What type of receptor are insulin receptrs?

A

receptor kinases

34
Q

What provides for a reversible method for altering protein function?

A

protein phosphorylation

35
Q

What can proteins get phosphorylated onto?

A

any hydroxyl group, introduces large negative charge into protein structure

36
Q

What is the insulin receptor?

A

a dimeric tyrosine kinase

37
Q

Name a rare autosomal recessive genetic trait with mutations in the gene for insulin receptor causing growth retardation, decreased muscle mat, no subcutaneous fat and elfin facial appearance?

A

leprechaunism/Donohue syndrome

38
Q

Which autosoma recessive trait causes severe insulin resistance, hyper glycaemia, developmental abnormalities and acanthosis nicrigans?

A

rabson mendenhall syndrome

39
Q

Where are ketone bodies formed?

A

liver mitochondria

40
Q

What organs are ketone bodies important molecules of energy for?

A

heart muscle

renal cortex

41
Q

What does fatty acid oxidation yield?

A

acetyl CoA

42
Q

What can accumulation of ketone bodies lead to?

A

acidosis

43
Q

What type of diabetes is ketoacidosis associated with?

A

type 1

Endocrinology (25 decks)

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