LECTURE 20 - hormonal control of blood sugar Flashcards

1
Q

How is energy stored in our body?

A
  • stored as fat

- stored as glycogen and triglycerides

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2
Q

How are carbohydrates metabolised?

A

Glycogenesis

  • conversion of GLUCOSE –> GLYCOGEN
  • occurs in liver and muscles
  • glycogen soured within cytoplasmic granules

Glycogenolysis
- conversion of glycogen –> glucose

Gluconeogenesis

  • synthesising glucose from non-carbohydrate sources
  • lactic acid, amino acids and glycerol can be converted into glucose
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3
Q

What are the key players in fuel metabolism?

A

LIVER

  • glucose uptake
  • glycolysis
  • gluconeogenesis
  • de novo lipogenesis

PANCREAS
- insulin and glucagon secretion

ADIPOSE TISSUE

  • glucose uptake
  • triglyceride storage
  • fatty acid release

MUSCLE

  • glucose uptake
  • glycogen storage
  • triglyceride storage
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4
Q

What is the importance of blood sugar control?

A
  • ensures energy can be given on demand

- carbohydrate is the body’s primary energy source in cell metabolism

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5
Q

What are the consequences of too high blood sugar?

A
Hyperglycaemia 
Symptoms:
- none
- polyuria 
- thirst
- weight loss
- fatigue 

Consequences:

  • neuropathy
  • nepropathy
  • heart disease
  • cataracts and blinders
  • diabetic coma
  • death
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6
Q

What are the consequences of too low blood sugar?

A
Hypoglycaemia 
Symptoms:
- irritability, fatigue 
- food cravings 
- headaches 
- dizziness 
- shaking 
- confusion 

Consequences:

  • loss of consciousness
  • accidents and injury
  • weight gain
  • reduced IQ
  • brain abnormalities
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7
Q

What are the Islets of Langerhans?

A
  • insulin levels regulate the secretion of glucagon
  • alpha cells secrete glucagon
  • beta cells secrete insulin
  • delta cells secrete somatostatin
  • alpha cells see high levels of insulin thus don’t produce glucagon
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8
Q

Describe the structure of insulin and how it is processed

A
  • insulin is a peptide hormone
  • gene synthesis, gene is transcribed and mRNA passed onto RER
  • initially produce preproinsulin
  • preproinuslin has a signal peptide an A, B and C chain
  • within lumen of RER, endopeptidases will cleave off signal peptide, leaving proinsulin
  • proinsulin gets packaged into vesicles (disulphide bridges between A and B chain occur in these vesicles)
  • vesicles are secreted towards Golgi apparatus, once here, contents released onto Golgi where there are more endopeptidases where the C chain gets cleaved off
  • mature insulin and C chain packaged into secretory vesicles (in certain cases there is proinsulin)
  • insulin needs to be held with zinc
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9
Q

How is insulin secreted?

A
  • insulin stored in vesicles
  • high glucose levels = we want insulin secretion
  • glucose cannot cross plasma membrane => requires transporters which are the glucosensors (GLTU2 transporters (bidirectional) on pancreas)
  • if blood supply has high levels of glucose => diffusion of glucose into the cell through transporters
  • a mechanism is required to keep glucose in cell to avoid equilibrium, this is phosphorylation
  • glucokinase in pancreas (hexokinase in liver) adds phosphate to form glucose-6-phosphate - can be metabolised
  • metabolism = ATP production
  • on beta cell, K channels are open when bound to ADP - usually net movement = K out leaving inside relatively -ve ~-70mV
  • glucose entering = channels close due to more ATP = K cannot move out, build up in cell = -70 gets more +ve
  • at -50mV, voltage gated Ca channel open allowing Ca to enter cell => exocytosis
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10
Q

How does insulin signalling occur?

A
  • insulin binds to receptor

- in liver, more GLUT transporters can be brought to surface, these are GLUT4

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11
Q

What are the metabolic effects of insulin?

A
  • more glucose and amino acids imported
  • glucose stored as glycogen
  • amino acids stored as proteins
  • fats stored as fatty acids such as adipose tissue
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12
Q

What is glucagon?

A
  • hormone that has antagonistic action to insulin
  • released by alpha cells of the Islands of Langherhans
  • secreted in response to LOW blood sugar
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13
Q

How is glucagon synthesised?

A
  • synthesised by proteolytic processing in the alpha cells from proglucagon
  • made from a gene that also exists in the intestines
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14
Q

What are the actions of glucagon?

A
  • promotes gluconeogeneis
  • promotes glycogenolysis
  • increases ketogenesis and lipolysis (the formation of ketone bodies from fatty acid oxidation)
  • ketogenesis occurs in the liver, lipolysis occurs in adipose tissue
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15
Q

What other hormones are involved in glucose homeostasis?

A
  • growth hormone
  • epinephrine
  • glucocorticoids
  • somatostatin: inhibitor of other peptide, produced by delta cells
  • GLP-1
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16
Q

What is GLP-1?

A

Glucagon-like peptide (GLP-1)

  • member of incretin family
  • made from glucagon gene
  • has 3 main roles
    1. tells brain you are full
    2. moving things to stomach more slowly
    3. promotes insulin like action by preparing you for insulin release
  • receptors on beta cells
  • has an enzymes that attacks it = dipeptidyl peptidase IV (DPP4)
17
Q

What are some GLP-1 analogues?

A

Exendin-4 (exenatide)

  • has related structure
  • resists DDP IV degradation subcutaneous injection

Liraglutide

  • albumin binding
  • decreased degradation by DDP IV subcutaneous injection
18
Q

What is liraglutide used for?

A
  • used as an anti-obesity therapy
  • not broken down by DPP4, can then promote insulin and tell the brain you are full
    (GLP1 broken down by DPP4)
19
Q

What are SGLT2 inhibitors?

A
  • sodium-glucose co-transporter inhibitors
  • can treat obesity
  • high levels of glucose normally result in glucose reabsorption
  • too much glucose = overloaded transporters = cannot reabsorb all of it = glucose in urine
  • diabetics have high levels of glucose in the blood, quick fix = dumping XS glucose in urine, this happens by stopping reabsorption thus SGLT2 inhibitors used
20
Q

What is insulin resistance and what does it lead to?

A
  • an impaired biological response to insulin
  • insulin sensitivity decreases as abdominal fat increases
  • leads to Type 2 diabetes