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REB > 7. Insulin > Flashcards

7. Insulin Flashcards

1
Q

What type of hormone is insulin?

A

Polypeptide

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2
Q

Which cells produce insulin?

A

Beta cells of islet of Langerhans in pancreas

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3
Q

What is the primary function of insulin?

A

Facilitate the uptake of glucose into cells

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4
Q

Which organs do not require insulin for glucose uptake?

A

Brain
Liver
Kidneys

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5
Q

What are the functions of somatostatin?

A

Suppress release of insulin and glucagon
Suppress release of gastrin, CCK
Inhibit the release of GH and TSH

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6
Q

What is the function of glucagon?

A

Raises glucose levels by enhancing gluconeogenesis and glycogenolysis

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7
Q

Describe the synthesis of insulin up to proinsulin

A

mRNA is translated as a single chain precursor, preproinsulin
Signal peptide is removed by endopeptidases in the RER to make proinsulin

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8
Q

What are the 3 domains of proinsulin?

A

Amino-terminal B chain
Carboxy-terminal A chain
Connecting C peptide

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9
Q

What is the structure of mature insulin?

A

51 amino acids

2 unbranched peptide chains linked by 2 disulphides

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10
Q

What converts proinsulin into mature insulin?

A

PC2 and 3

Carboxypeptidase E

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11
Q

Describe the events leading up to insulin release

A
  1. Glucose enters through GLUT2
  2. Glucose is metabolised via glucokinase
  3. ATP is generated
  4. ATP-sensitive K+ channels close
  5. Depolarisation of cell membrane due to increased intracellular K+
  6. Opens voltage-sensitive Ca++ channels, Ca enteres
  7. Increased Ca++ triggers release of insulin containing secretory granules
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12
Q

What are the causes of hyperinsulinism?

A

Insulinomas
Congenital
Drug induced
Too much exogenous insulin

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13
Q

What are 3 genetic defects that can result in hyperinsulinism?

A

Katp channel disorders
Glucokinase gain-of-function mutation (beta cell releases insulin at lower glucose levels)
Hyperammonaemic hyperinsulinism

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14
Q

What is hyperammonaemic hyperinsulinism?

A

Gain-of-function mutation of glutamate dehydrogenase
Beta cells secrete insulin in response to an increase in the ATP/ADP ratio caused by AA breakdown and formation of alpha-ketoglutarate
More insulin is secreted

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15
Q

What regulates insulin release?

A

Glucose and amino acids
Glucagon and somatostatin
GIP and GLP

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16
Q

Where is glucagon produced?

A

Pancreatic alpha-cells
Intestinal neuroendocrine L-cells
Brain

17
Q

What stimulates glucagon secretion?

A

Low blood glucose and low insulin
Rise in amino acids following a protein meal
Adrenaline and noradrenaline

18
Q

What is proglucagon converted to in pancreatic alpha cells?

A

Glucagon
Glicentin-related pancreatic peptide
MPF

19
Q

What is proglucagon converted to in intestinal neuroendocrine L-cells?

A

Glucagon-like peptide-1
GLP-2
Glicentin

20
Q

What are the functions of GLP-1?

A

Stimulates insulin secretion
Stimulates somatostatin release
Inhibits glucagon secretion

21
Q

What are the functions of glicentin?

A

Stimulates insulin secretion
Inhibits gastric acid secretion
Regulates gut motility

22
Q

What is the short-term function of insulin?

A

Increased transport of glucose, amino acids and K+ into insulin sensitive cells

23
Q

What are the intermediate functions of insulin?

A

Stimulate the entry of AAs into cells and protein synthesis
Inhibit protein degradation
Activate glycolysis and glycogen synthesis
Inhibit glycogenolysis and gluconoegenic enzymes

24
Q

What is the delayed function of insulin?

A

Increase in mRNAs for lipogenic and other enzymes

25
Q

What type of receptor is an insulin receptor?

A

Tyrosine kinase

26
Q

What domains are in the alpha subunit of an insulin receptor?

A

Insulin binding domain

27
Q

What domains are in the beta subunit of an insulin receptor?

A

ATP-binding

Tyrosine kinase

28
Q

What are the events following insulin binding to its receptor?

A
  1. Binding causes autophosphorylation of tyrosines in beta subunits
  2. Activated receptor phosphorylates intracellular proteins
  3. Activation of signalling pathways
29
Q

How is the insulin receptor regulated?

A

After binding the receptor is internalised

Insulin is degraded in lysosomes

30
Q

Which glucose transporter is insulin responsive?

A

GLUT 4

31
Q

Which glucose transporter is used by the liver?

A

GLUT 2

32
Q

Which glucose transporter is used by the brain?

A

GLUT 3

33
Q

What is the half life of circulating insulin?

A

4-6 minutes

34
Q

Besides diabetes mellitus, what are other reasons for hyperglycaemia?

A 
Genetic defects of beta function of insulin action
Diseases of exocrine pancreas
Endocrinopathies
Drug/chemical induced
Infections
35
Q

What are the symptoms of type 1 diabetes mellitus?

A 
Polydipsia
Polyuria
Glycosuria
Weight loss with increased appetite
Fatigue
Nausea
Vomiting
Diabetic ketoacidosis
36
Q

What are the symptoms of type 2 diabetes mellitus?

A 
Polydipsia
Polyuria
Glycosuria
Increased appetite
Fatigue
Blurred vision
Slow-healing infections
Impotence in men
37
Q

What is diabetic ketoacidosis?

A

Without insulin the body can’t use glucose and breaks down fat to use for energy
When fats are broken down, ketones are produced in the liver
If levels of ketones can’t be excreted in urine they build up in the blood, leading to ketoacidosis

38
Q

What are the symptoms of ketoacidosis?

A

Shortness of breath
Breath that smells sweet
Nausea, vomiting
Dry mouth

REB (29 decks)

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