Insulin Resistance and Type 2 Diabetes Flashcards

1
Q

What is the most important factor in type 2 diabetes development?

A

Age

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2
Q

Is the influence of genetics on type 2 diabetes usually monogenic or polygenic?

A

Polygenic

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3
Q

What is the response of a normal subject to the homeostatic model assessment of insulin resistance and B-cell resistance?

A

Early increase in blood glucose
Absorbed and metabolised by tissues
Decrease to fasting glucose concentration

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4
Q

What is the response of a diabetic subject to the homeostatic model assessment of insulin resistance and B-cell resistance?

A

Early increase in blood glucose

Remains elevated - decreased tissue efficiency in glucose uptake

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5
Q

What is the response of a prediabetic subject to the homeostatic model assessment of insulin resistance and B-cell resistance?

A

Normal fasting blood glucose levels

‘Diabetic’ curve - good indicator of insulin and B-cell resistance

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6
Q

What are the 3 types of cells in the islets of Langerhans and what are their roles?

A

Alpha - produce glucagon - stimulates glucose release from liver
Beta - produce insulin
Delta - produce somatostatin - suppresses insulin and glucagon secretion

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7
Q

What is the effect of the increased insulin resistance in prediabetes?

A

Causes increased B-cell function - to compensate - make more insulin

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8
Q

How does the blood insulin level change after diabetes onset and why?

A

Decreases

Decreased B-cell function - decreased capacity to compensate - B-cell failure - requires exogenous insulin injection

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9
Q

What is the evidence of B-cell adaptation in diabetes in mice?

A

Leptin receptor mutant mice - eat excessively
Insulin resistant at 12 weeks - B-cells enlarge to compensate
At 24 weeks B-cells decrease in number and size - fail due to glucolipotoxicity
Mice become diabetic

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10
Q

What are the effects of insulin resistance?

A

Hyperglycaemia - due to decreased skeletal muscle glucose uptake, increased liver glucose output
Hyperlipidaemia - due to increased lipolysis

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11
Q

What may be the mechanism behind B-cell failure?

A

Glucotoxicity, lipotoxicity, oxidative stress

Cause B-cell apoptosis

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12
Q

How might senescent cells be linked to diabetes?

A

Drive insulin resistance

Drive diabetes complications

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13
Q

How do senescent cells cause B-cell damage?

A

SASP - pro-inflammatory

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14
Q

What is the glucose-induced insulin secretion from a normally functioning islet?

A

1st phase release
Smaller 2nd phase
Return to fasting insulin level

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15
Q

What is the glucose-induced insulin secretion from an early T2D islet?

A

Loss of 1st phase release
Delayed 2nd phase release
Insulin levels remain elevated

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16
Q

What is the glucose-induced insulin secretion from a late T2D islet?

A

Loss of 1st and 2nd phase releases - no insulin release

Insulin levels remain at fasting level

17
Q

What is an advanced glycosylation end-product (AGE)?

A

Adduct of proteins and carbohydrates

18
Q

Why do AGEs form?

A

High carbohydrate level for long time

19
Q

What is the process of AGE formation?

A

Carbohydrate reacts with amino group of protein - f0rms Schiff base
Schiff base rearranges - forms Amadori product
Amadori product reacts with amino group of another protein - forms cross-linked AGE - 2 protein molecules linked together

20
Q

What are the effects of AGE formation?

A

Can occur multiple times - form protein aggregates
Activates pro-inflammatory signalling
Cause tissue stiffness and loss of elasticity

21
Q

How does AGE accumulation change with age and in diabetes?

A

Increases with age

Accelerated in diabetes

22
Q

Which proteins are prone to AGE formation?

A
Glycated haemoglobin (HbA1c)
Proteins with slow/absent turnover - e.g. eye lens crystallins
23
Q

Which environmental source do some AGEs come from?

A

Dietary intake

24
Q

Which affects of AGEs contribute to old-age frailty?

A
Brain - AD
Eyes - cataract formation
Blood vessels - hypertension
Bone - osteoporosis, fractures
Muscle - sarcopenia
25
Q

What is dietary restriction?

A

Decreasing caloric intake by >=30%

26
Q

How does dietary restriction affect mice, flies, and worms?

A

Increases lifespan

Decreases circulating insulin and IGF-1 levels - shows increased insulin sensitivity

27
Q

How could the benefits of dietary restriction be achieved in diabetics without undergoing the programme?

A

Deduce pathways behind effects

Develop small chemical mimetics of DR

28
Q

How might senolytics be useful in treating diabetes?

A

Specifically eliminate senescent cells - suppress SASP

May improve functioning of cells in islets of Langerhans - positive metabolic effects