Regulation of Blood Glucose

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1
What is secreted when blood glucose concentration increases?
Insulin
2
What cells in the pancreas secrete insulin?
Beta cells
3
Describe the basic structure of insulin.
Two peptide chains joined by three disulfide bridges
4
Describe how insulin is synthesised.
Prepoisnulin —> proinsulin —> activated insulin
5
Where in the cell does proinsulin mature into active insulin?
Golgi apparatus
6
What is the co factor for insulin synthesis?
Zinc
7
How does glucose enter beta cells?
Via GLUT2 transporter proteins
8
What GLUT transported is glucose dependent?
GLUT2
9
What enzyme converts glucose into glucose 6 phosphate?
Hexokinase /Glucokinase
10
C peptide is a product that indicates level of what hormone?
Insulin
11
How is glucose stored in cells?
As a hexamer
12
What enzyme acts as the glucose sensor for insulin secretion?
Glucokinase
13
Does glucokinase have a high or low Km and what effect does this have?
High Km, high concentrations of glucose are required for insulin secretion to occur
14
Influx of what ion triggers insulin secretion?
Calcium
15
Briefly describe how is insulin is secreted from beta cells starting with increased glucose concentration.
High glucose —> Increase ATP:ADP ratio —> ATP dependent potassium channels close —→ membrane depolarisation —> Caclium channels open —> Calcium ion influx —> insulin secretion
16
Describe what channels are open during sub stimulatory glucose concentrations and what happens when they become stimulatory?
When glucose concentrations are high ATP dependent potassium channels close causing depolarisation which triggers calcium channels to open
17
In how many phases does pancreatic beta cells release insulin in?
Two phases
18
Describe the first phase in the release of insulin.
Rapidly triggered in response to increased blood glucose levels
19
Describe the second phase in the release of insulin.
Slow and sustained release of insulin from vesicles
20
What are other signals that can stimulate insulin release?
Amino acids; GLP1; GIP; Fatty acids; CCK
21
How do amino acids stimulate insulin release?
Enter through transporters to depolarise membrane causing calcium channels to open
22
What is excessive basal insulin secretion linked to?
Insulin resistance
23
What occurs to the insulin receptor when blood glucose concentration is low?
It is inactive
24
How does the insulin receptor work when blood glucose concentration increases?
Insulin receptor substrate binds to insulin receptor; Insulin receptor is autophosphorylated via tyrosine residues; IRS is then phsophrylated
25
What processes occur when blood glucose conetration decreases?
Gluconeogenesis; Glycogenolysis; Lipolysis
26
What precursor is glucagon made from?
Proglucagon
27
How do glucagon and adrenaline work via second messenger?
Activates enzyme that converts AMP into cAMP
28
What are some insulin counter regulatory hormones?
Cortisol; Growth Hormone; Adrenaline; Glucagon
29
What are corticosteroids synthesised from?
Cholesterol
30
What regulates the secretion of corticosteroids?
HPA axis
31
What is the main role of cortisol?
Resists stress and inflammation and helps maintain blood pressure
32
In what conditions cause cortisol to be increased?
Low blood glucose conditions
33
Describe the metabolic effects of cortisol.
In the liver it enhances gluconeogeneiss; In the muscle it inhibits glucose uptake and stimulates protein degradation
34
What stimulates the release of growth hormone?
Growth hormone releasing hormone (GHRH)
35
What inhibits the release of growth hormone?
Somatostatin
36
How does the growth hormone act?
Anatgonist of insulin causing blood glucose concentrations to rise
37
What secretes growth hormone?
Anterior pituitary gland
38
Describe the incretin effect.
Oral glucose has a greater insulin response than IV glucose
39
What cells secrete GLP1?
L cells in the small intestine
40
What cells secrete GIP?
K cells in the small intestine
41
In what conditions is GLP1 and GIP secreted in?
Secretion in response to ingestion of a meal or glucose - high blood glucose
42
Describe the proteolytic degradation of GLP1 and GIP.
DPP4 breaks down GIP and GLP1
43
What type of receptors doe GLP1 and GIP act on?
G coupled protein receptors
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