biochem of glucose + insulin Flashcards
(70 cards)
1
Q
what type of hormone is insulin?
A
-peptide hormone
2
Q
what level is fasting blood sugar in a diabetic?
A
> 7mM
3
Q
what level is fasting blood sugar in a healthy patient?
A
4-6mM
4
Q
what level is fasting blood sugar in a prediabetic?
A
6-7mM
5
Q
what level is fasting blood sugar in hypoglycaemia?
A
<4mM
6
Q
what do beta cells in the pancreatic islet secrete?
A
insulin
7
Q
what do alpha cells in the pancreatic islet secrete?
A
glucagon
8
Q
what do delta cells in the pancreatic islet secrete?
A
somatostatin
9
Q
what do PP cells in the pancreatic islet secrete?
A
pancreatic polypeptide
10
Q
how is insulin secreted into plasma from the pancreatic islet?
A
- preproinsulin is synthesised in rough endoplasmic reticulum of pancreatic beta cells
- preproinsulin is cleaved to form insulin
- connecting C peptide is also cleaved
10
Q
how is insulin secreted into plasma from the pancreatic islet?
A
- preproinsulin is synthesised in rough endoplasmic reticulum of pancreatic beta cells
- preproinsulin is cleaved to form insulin
- connecting C peptide is also cleaved
11
Q
why would C peptide be measured?
A
-to see how much insulin body has actually produced as when insulin is injected C peptide is not produced
12
Q
what is insulin lispro?
A
short acting insuli
13
Q
what advantage does short acting insulin give?
A
it reduces chances of hypoglycaemia
14
Q
when is short acting insulin normally administered?
A
within 15 minutes of beginning of meal
15
Q
what is short acting insulin usually given with for type 1 diabetes?
A
-must be used with longer acting insulin for type 1 diabetes unless used for continuous infusion
16
Q
whats an example of long acting insulin?
A
insulin glargine
17
Q
when is long acting insulin usually administered?
A
-as a single dose at bedtime
18
Q
what does the primary structure of pro insulin contain?
A
- A chain
- B chain
- C peptide
19
Q
what do the A chain and B chain of the primary structure of pro insulin contain and why?
A
-disulphide bridges between cystene residues which help provide the tertiary structure of the 3D structure
20
Q
what allows C peptide to be cleaved in proinsulin?
A
Ca+ dependant endopeptidases (PC2 and PC3)
21
Q
how does glucose enter beta cells for glycolysis?
A
- through GLUT2 glucose transporter by diffusion (as glucose rises in blood a concentration gradient will be created and glucose will enter beta cells)
- glucose is then phosphorylated into glucokinase and glycolysis can occur to produce ATP
22
Q
how is insulin secreted from beta cells?
A
- glycolysis causes generation of ATP
- generation of ATP closes ATP sensitive potassium channel
- this depolarises beta cell membrane
- depolarisation of beta cell membrane allows voltage gated calcium channels to open
- influx in Ca2+ allows the insulin secretory granules to fuse with the cell membrane and release insulin into plasma
23
Q
what is the role of glucokinase?
A
it is responsible for turning glucose into glucose-6-phosphate
24
what occurs to glucose phosphorylation as glucose levels change from 4.5mmol/l to 5.5mmol/l?
a massive change in glucose phosphorylation (so a massive increase in glucokinase)
25
what molecule would dictate the level of glucose that would be present in the plasma: hexokinase or glucokinase?
glucokinase- as it's Km for glucose lies in the physiological range of concentrations
26
what is Vmax?
-maximal rate of reaction at unlimited substrate concentration
27
what is Km?
50% of Vmax
28
what does increase in ATP in beta cell do to ATP potasium channel?
it inhibits it
29
what does inhibition of ATP potassium channel in beta cells lead to?
-depolarisation of membrane
30
what does depolarisation of beta cell membrane lead to?
opens the voltage-gated calcium channel causing an influx of calcium
31
what does an increase in internal Ca2+ in the beta cell lead to?
fusion of secretory vesicles with the cell membrane and release of insulin
32
what glucose level is insulin produced at?
above 5mM
33
how many times is insulin usually secreted in healthy individuals?
-its biphasic (in two phases)
34
what is the first phase for insulin secretion for?
- this is when glucose is initially decreased in blood
| - it is a sharp peak of insulin secretion which helps prevent rapid hypoglycaemia
35
how is the second phase of insulin secretion different to the 1st?
-the 2nd phase is more tuned to the insulin requirement related to glucose intake (amount and duration) and tends to be lower and longer
36
what is the first pool of insulin granules called?
RRP- readily releasable pool
37
what % of insulin granules are in the readily releasable pool?
5%
38
how are the insulin from the second pool of granules released?
the second pool must undergo mobilisation
39
which pool of insulin granules does the first phase tend to use?
the RRP ( readily releasable pool)
40
what causes type 1 diabetes?
-an autoimmune destruction of the pancreatic beta cells
41
how does type 2 diabetes present to begin with compared to later on?
to begin with= usually presents with hyperinsulinemia as beta cells try to compensate for the hyperglycaemia caused by insulin resistance
later= often presents with decline in beta cell function, presumably due to prolonged over stimulation following years of hyperglycaemia
42
how is gestational diabetes treated?
- lifestyle advice
| - sometimes metformin to improve insulin sensitivity
43
True or False
The diagnostic criteria for gestational diabetes is lower than other forms of diabetes?
True
44
what is MODY (maturity onset diabetes of young)?
a monogenic disease with common clinical features to both type 1 and type 2 diabetes. Beta cell dysfunction but not autoimmune destruction
45
what is neonatal diabetes?
-a rare form of monogenic diabetes much of which is caused by mutations in the glucose sensing machanism (eg in ATP sensitive K channel)
46
what does the ATP sensitive K channel made up of?
consists of two proteins with 4 subunits:
- an inward rectifier subunit (Kir) (has 4 subunits)
- a sulphonylurea receptor (SUR) (has 4 subunits)
47
what is the pore inward rectifier subunit (Kir) called?
Kir6
48
what is the regulatory subunit of the sulphonylurae receptor called?
SUR1
49
what does a mutation in Kir6.2 cause?
-neonatal diabetes
50
what does the sulphonylurea class of drugs do to KATP?
directly inhibit KATP
51
what are examples of sulphonylurea class drugs?
- tolbutamide
| - glibenclamide
52
what affect does diazoxide have on KATP?
dizoxide stimulates KATP with inhibits insulin secretion
53
why is there higher blood glucose in MODY ?
- the glucokinase activity is impaired
- glucose threshold required to secrete insulin is increased meaning more glucose is needed before some insulin can be produces
54
what mutation is usually in MODY?
mutation in HNF transcription factor 1 and 3
55
what is leprechaunism/ Donohue syndrome?
- rare autosomal recessive genetic trait
| - mutation in the gene for insulin receptor causing severe insulin resistance
56
how may leprechaunism present?
- elfin facial appearance
- growth retardation
- absence of subcutaneous fat , decreased muscle mass
these are all due to defects in insulin binding or insulin receptor signalling
57
what is Robson Mendenhall syndrome?
- rare autosomal recessive genetic trait
| - causes severe insulin resistance, hyperglycaemia and compensatory hyperinsulinemia
58
how does Robson Mendenhall syndrome tend to present?
- ancanthosis nigricans (hyperpigmentation)
- have severe insulin resistence, hyperglycaemia and compensatory hyperinsulinemia
- fasting hypoglycaemia (due to hyperinsuliaemie)
- prone to diabetic ketoacidosis
59
what is one of the most damaging complications of severe insulin resistence?
Diabetic ketoacidosis
60
what are the symptoms of diabetic ketoacidosis?
- vomiting
- dehydration
- increased heart rate
- distinctive smell on breath (acetone smell)
61
where are the ketone bodies derived from?
-formed in liver mitochondria
derived from acetyl-CoA which is from beta oxidation of fats
62
how do ketone bodies leave the liver?
they diffuse into blood stream and to peripheral tissues
63
what are ketone bodies important molecules for?
- ketone bodies are important molecules of energy for heart muscle and renal cortex
- they are converted back to acetyl-CoA which enters the TCA cycle
64
what is insulins role in lypolysis?
insulin normally inhibits lipolysis (breakdown of fat) reducing risk of ketone body overload
65
is diabetic ketoacidosis more common in type 1 or type 2 diabetes?
type 1!!!!
66
why is diabetic ketoacidosis more common in type 1 diabetes?
as in type 1 diabetes the patient may forget to take their insulin supplementation and hyperglycaemia continues where as in type 2 diabetes there is still some inhibition of lypolysis byt can occur as insulin resistence and deficiency increases alongside increase in glucagon
67
what stimulates the secretion of somatostatin from delta cells?
-Growth hormone
68
what is the role of somatostatin?
-regulates secretion of insulin, glucagon nad growth hormone
69
what is the role of pancreatic polypeptide?
-regulates pancreatic endocrine and exocrine functions
