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LS1 Metabolism > 16 - Endocrine pancreas and diabetes > Flashcards

16 - Endocrine pancreas and diabetes Flashcards

1
Q

What do beta-cells in the islets of pancreas produce?

A

Insulin

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2
Q

What is the major cell-type in the islet of Langerhans?

A

beta-cells (75%)

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3
Q

What is the second most common cell type in the islets of Langerhans?

A

alpha-cells (20%)

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4
Q

What do alpha-cells secrete?

A

glucagon

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5
Q

How do alpha- and beta- cells store their hormones intracellulary?

A

In membrane-bound vesicles prior to secretion (storage granules).
Each cell may contain up to 13,000 storage vesicles!

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6
Q

How are alpha- and beta- cells’ ultrastructure specialised for the role as endocrine cells?

A

Extensive rER
well-defined golgi apparatus
lots of mitochondria
well-define system of microtubules and microfilaments (very organised cell structure)

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7
Q

How many covalent disulphide bonds hold the A and B polypeptide chains of insulin together?

A

2

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8
Q

There are two inter-chain disulphide bonds in insulin, where is the third found?

A

Intra-chain disulphide bond within the A chain

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9
Q

Where in the cell are the disulphide bonds of insulin (proinsulin at this point) formed?

A

ER lumen

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10
Q

Where in the cell is the C peptide cleaved from the A and B chains of proinsulin, forming insulin?

A

Post-Golgi in secretory vesicles

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11
Q

Where in the cell are the ribsomomes that synthesise pre-proinsulin found?

A

Attached to the rER

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12
Q

What is the ‘pre’ part of pre-proinsulin and what happens to it?

A

It is a signal peptide that ensures that correct co-translational translocation (translocation from ribosome on outside of ER through membrane into the lumen of the ER)

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13
Q

What happens to the proinsulin inside the ER cisternal space?

A

It folds to ensure correct alignment of cysteine residues and that the correct disulphide bonds form

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14
Q

What two peptides are proteolytically cleaved from proinsulin inside the storage vesicles?

A

C peptide and a chain of four basic amino acids

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15
Q

Where is the C peptide and the chain of four basic amino acids found in proinsulin?

A

middle

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16
Q

What does the storage vesicle from beta-cells contain when it is released?

A

Insulin and C peptide - equimolar amounts

small amount of unchanged proinsulin

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17
Q

Why is C-peptide a useful marker of endogenous insulin release?

A

Because insulin and C-peptide are released from beta-cells into blood plasma in equimolar amounts

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18
Q

Why would you be interested in measuring plasma C-peptide levels in patients receiving insulin injections?

A

To monitor any endogenous insulin secretion

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19
Q

How is insulin transported?

A

Free in blood (not bound to a transport protein)

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20
Q

What complexes with insulin in storage granules inside the beta-cell?

A

Insulin forms a crystalline zinc-insulin complex

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21
Q

What are the major target tissues for insulin?

A

liver, skeletal muscle and adipose tissue (though insulin is required for the normal growth and development of most tissues in the body)

22
Q

Where does insulin interact on the target cells?

A

Insulin receptors on the surface of target cells

23
Q

What receptor family are insulin receptors a member of?

A

Tyrosine kinase receptor family

24
Q

What are the short-term effects (sec/hours) of an increase in the concentration of insulin circulating?

A

Changes in the activities of pre-existing functional proteins such as enzymes and transport molecules in target tissues

25
Q

What types of metabolism does insulin affect?

A

carbohydrate, lipid and protein metabolism

26
Q

What are the long-term effects (hours/days) of an increase in the concentration of insulin circulating?

A

It stimulates the synthesis of new proteins and DNA replication, which affect cell growth and division

27
Q

What are the effects of insulin on the liver?

A

Increase glycogenesis and decrease glycogenolysis
Increase glycolysis
Decrease gluconeogenesis
Increase lipogenesis and esterification of fatty acids
Decrease ketogenesis
Increase amino acid uptake and protein synthesis
Decrease proteolysis

28
Q

What are the effects of insulin on skeletal muscle?

A

Increase glucose transport into muscle
Increased glycogenesis and decreased glycogenolysis
Increased glycolysis
Increased amino acid uptake and protein synthesis
Decreased proteolysis

29
Q

What are the effects of insulin on adipose tissue?

A

Increased glucose transport into adipose tissue
Increased glycolysis
Decreased lipolysis
Increased lipogenesis and esterification of fatty acids
Increased lipoprotein lipase activity in the capillary bed of tissues such as adipose tissue
Increased amino acid uptake

30
Q

What is an effect of insulin on the caridac muscle?

A

Decreased proteolysis

31
Q

Which factors stimulate insulin secretion?

A

Metabolites - glucose, amino acids, fatty acids
GI tract hormones-gastrin, secretin, CCK (cholecystokinin)
Neurotransmitters - acetyl choline (ACh)

32
Q

Which factors inhibit insulin secretion?

A

The neurotransmitters adrenaline and noradrenaline

33
Q

Describe the structure of glucagon

A

Single polypeptide chain without disulphide bonds. It has a flexible 3D structure that takes up its active conformation upon binding to its target receptors on the surface of target cells

34
Q

How is glucagon synthesised by the pancreatic alpha-cells?

A

it is synthesised as pre-proglucagon and undergoes post-translational modification to produce the biologically active molecule

35
Q

What are the effects of glucagon on the liver?

A

Increased glycogenolyis and decreased glycogenesis
Increased gluconeogenesis
Increased ketogenesis

36
Q

What are the effects of glucagon on adipose tissue?

A

Increase lipolysis

37
Q

What is the mechanism of action of glucagon?

A
  1. Binds to G protein-coupled receptor (GPCR)
  2. Binding activates enzyme adenylate cyclase, which increases cyclic AMP (cAMP) intracellularly
  3. High levels of cAMP activate protein kinase A (PKA)
  4. PKA phosphorylates and therefore activates a number of important enzymes in target cells
38
Q

What type of hormone is glucagon?

A

water-soluble peptide hormone

39
Q

What type of hormone is insulin?

A

water-soluble peptide hormone

40
Q

What type of receptor does glucagon bind to in the cell membrane of target cells?

A

G protein-coupled receptor

41
Q

How does binding of glucagon activate the GPCR?

A

Causes the dissociation of the alpha-sbunit of the G protein which activates the effector protein (adenylate cyclase)

42
Q

G-protein coupled receptors’ general mechansim can be described as:

  1. Binding causes dissoication of alpha-subunit from G protein
  2. Causing activation of effector protein
  3. Causing formation of second messenger
  4. Causing activation of protein kinase
  5. Causing phosphorylation of target proteins and cellular response
    (i) What is the name of the effector protein upon glucagon binding?
    (ii) What is the name of the second messenger in the glucagon signalling pathway?
    (iii) What is the name of the protein kinase in the glucagon signalling pathway?
A

(i) adenyl cyclase
(ii) cyclic AMP (cAMP)
(iii) protein kinase A (PKA)

43
Q

What is the major factor that increases the rate of glucagon secretion?

A

Decrease in blood glucose concentration

44
Q

What factors inhibit glucagon secretion?

A

Insulin

Increase in blood glucose concentration

45
Q

Why can ketoacidosis lead to abdominal pain?

A

Overactivation of the sympathetic nervous system due to the blood pressure drop caused by dehydration. The SNS redirects blood towards heart which can lead to nausea and vomiting

46
Q

Why is ketoacidosis a diabetic emergency?

A

low blood pH coupled with low blood pressure can lead to coma and eventually death

47
Q

How do you treat ketoacidosis?

A

Insulin
Fluids
Potassium - insulin drives K inside cells and therefore can cause hypokalemia
When BM gets to 12 want to add a bit of glucose, so indivudual doesn’t become hypoglycaemic

48
Q

Other than insulin, what treatment does a Type 1 diabetic require?

A
  1. Education on how to respond to a hypo -family awareness too
  2. Diabetic nurse - how to inject, use BM machine, fit around lifestyle
  3. Optician check ups
  4. Education on diet and exercise - regular mealtimes
49
Q

What life-threatening crisis can type 2 diabetic get?

A

HONK (hyperosmolar non-ketotic coma) - brought about by very high blood sugars ) >33mmol/L

50
Q

A 1% increase in HbA1c level results in a 12% increase in what type of event?

A

CVD events

51
Q

Other than blood sugar levels in diabetics, what other factors are important to control in order to reduce the risk of macrovasculature complications?

A

Cholesterol levels - diet, statins(?)

Blood pressure

LS1 Metabolism (18 decks)

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