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LR Endocrine > Insulin Resistance > Flashcards

Insulin Resistance Flashcards

1
Q

How does insulin reduce blood glucose? (3)

A
  • Acts in the liver to inhibit glucose production and stimulate storage as glycogen
  • Acts in skeletal muscle to stimulate glucose storage and use for energy
  • Acts in adipose tissue to stimulate glucose storage as triglycerides
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2
Q

Why are more free fatty acids found in the blood of diabetics?

A

Insulin inhibits the breakdown of triglycerides to free fatty acids

So this is defective in diabetes

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3
Q

When insulin resistance develops, organs become less responsive to insulin. What conditions may arise in this case?

A
  • Diabetes
  • Neurodegenerative disease e.g., alzheimers
  • CV disease
  • Liver disease
  • Cancers
  • Chronic kidney disease
  • Polycystic ovarian disease
  • Gout
  • Sleep apnoea
  • Acne
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4
Q

Describe the development of T2DM from insulin resistance

A
  • In response to initial insulin resistance, beta cells will compensate by producing more insulin
  • Eventually the beta cells cannot counteract insulin resistance any longer, meaning they fail and T2DM develops
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5
Q

Describe the development of alzheimer’s disease from insulin resistance

A

Defective insulin signalling leads to altered gene expression

Synaptic dysfunction occurs and memory is impaired

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6
Q

Insulin resistance is associated with heart failure. T/F

A

True

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7
Q

How is insulin resistance diagnosed?

A

Healthcare professionals should identify individuals with risk factors and check their blood glucose levels for pre-diabetes or diabetes

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8
Q

List some risk factors for insulin resistance

A
  • Overweight
  • Inactivity
  • Family history of diabetes
  • Genetics e.g., African American, Latino/Hispanic
  • PCOS
  • Gestational diabetes
  • Hypertension
  • Hyperlipidaemia
  • Heart disease
  • Smoking
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9
Q

Describe insulin binding and interaction with skeletal muscle

A
  • Insulin binds to the insulin receptor
  • Autophosphorylation occurs (as it is a tyrosine kinase receptor), causing downstream signalling
  • Glycogen breakdown is stopped
  • GLUT4 translocates to the cell membrane to allow glucose to enter the skeletal muscle cell
  • Glucose is converted to G-6-P to be stored as glycogen or used to produce ATP
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10
Q

Describe insulin resistance in terms of impaired insulin signalling e.g., skeletal muscle insulin resistance

A
  • Insulin binds to the insulin receptor but internal tyrosine kinase activity is decreased
  • Downstream pathways are dampened so…
  • Glycogen is still broken down to produce glucose and…
  • Glucose does not enter the cell to be stored as glycogen or used for ATP
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11
Q

Describe insulin resistance in terms of inflammation e.g., adipose tissue insulin resistance

A
  • Obesity-induced inflammation causes adipocytes to produce pro-inflammatory cytokines
  • This causes local insulin resistance i.e., adipocytes take up less glucose
  • The pro-inflammatory cytokines can also travel to peripheral tissues (e.g., liver, skeletal muscle) to cause systemic insulin resistance
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12
Q

Describe how glucose is usually used by the liver

A

Glucose is converted to G-6-P by glucokinase, then it is used to…

  • Form glycogen
  • Produce triglycerides
  • Generate energy and CO2
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13
Q

What is insulin’s main job in the liver?

A

Inhibiting gluconeogenesis (glucose synthesis)

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14
Q

Describe pathway-selective hepatic insulin resistance

A
  • In insulin resistance, gluconeogenesis can continue to occur
  • Excess glucose is found in the liver
  • This leads to increased lipid and triglyceride production
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15
Q

What is the gold standard method for measuring insulin sensitivity?

A

The hyperinsulinemic-euglycemic clamp

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16
Q

Describe how the hyperinsulinemic-euglycemic clamp is carried out

A
  • Catheter is inserted into the internal jugular vein and the carotid artery
  • A constant rate of insulin is infused to increase insulin level
  • Arterial glucose is measured and maintained at a euglycaemic level by infusing exogenous glucose accordingly
17
Q

How does the hyperinsulinemic-euglycemic clamp tell you anything about insulin sensitivity?

A

The more glucose that needs to be infused to keep arterial glucose constant, the higher insulin sensitivity is (that’s a good thing)

18
Q

Describe the role of extracellular matrix remodelling in muscle cell insulin resistance

A
  • Obesity/ high fat diet leads to inflammation
  • Structural proteins e.g., collagen in the ECM become significantly increased
  • ECM proteins interact with receptors on the cell membrane
  • Insulin resistance occurs
19
Q

As well as obesity/ high fat diet, what else can increase ECM collagen in muscle cells and result in insulin resistance?

A

Genetic deletion of matrix metalloproteinase 9 (MMP9)

LR Endocrine (12 decks)

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