Insulin Resistance and Type 2 Diabetes Flashcards
What is the most important factor in type 2 diabetes development?
Age
Is the influence of genetics on type 2 diabetes usually monogenic or polygenic?
Polygenic
What is the response of a normal subject to the homeostatic model assessment of insulin resistance and B-cell resistance?
Early increase in blood glucose
Absorbed and metabolised by tissues
Decrease to fasting glucose concentration
What is the response of a diabetic subject to the homeostatic model assessment of insulin resistance and B-cell resistance?
Early increase in blood glucose
Remains elevated - decreased tissue efficiency in glucose uptake
What is the response of a prediabetic subject to the homeostatic model assessment of insulin resistance and B-cell resistance?
Normal fasting blood glucose levels
‘Diabetic’ curve - good indicator of insulin and B-cell resistance
What are the 3 types of cells in the islets of Langerhans and what are their roles?
Alpha - produce glucagon - stimulates glucose release from liver
Beta - produce insulin
Delta - produce somatostatin - suppresses insulin and glucagon secretion
What is the effect of the increased insulin resistance in prediabetes?
Causes increased B-cell function - to compensate - make more insulin
How does the blood insulin level change after diabetes onset and why?
Decreases
Decreased B-cell function - decreased capacity to compensate - B-cell failure - requires exogenous insulin injection
What is the evidence of B-cell adaptation in diabetes in mice?
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
What are the effects of insulin resistance?
Hyperglycaemia - due to decreased skeletal muscle glucose uptake, increased liver glucose output
Hyperlipidaemia - due to increased lipolysis
What may be the mechanism behind B-cell failure?
Glucotoxicity, lipotoxicity, oxidative stress
Cause B-cell apoptosis
How might senescent cells be linked to diabetes?
Drive insulin resistance
Drive diabetes complications
How do senescent cells cause B-cell damage?
SASP - pro-inflammatory
What is the glucose-induced insulin secretion from a normally functioning islet?
1st phase release
Smaller 2nd phase
Return to fasting insulin level
What is the glucose-induced insulin secretion from an early T2D islet?
Loss of 1st phase release
Delayed 2nd phase release
Insulin levels remain elevated