Why does chronic hyperglycemia in type 2 diabetes reduce the effectiveness of insulin therapy over time, despite initially adequate doses?

💡 Explanation

Hyperglycemia causes prolonged insulin release, downregulating GLUT4 transporters in pancreatic beta cells, reducing their sensitivity to glucose and insulin. Because of this downregulation, insulin therapy becomes less effective over time, therefore requiring increased doses to maintain glycemic control, rather than improved glucose metabolism in other tissues.

• Why does maladaptive vasodilation occur during septic shock, compromising thermoregulation?
• Which consequence results when functional red blood cells decline?
• What causes long-term potentiation (LTP) at a glutamatergic synapse during associative learning?
• Why does administering a selective COX-2 inhibitor after cardiac surgery increase the risk of delayed sternal closure?
• Why does the risk of multiple gestations increase when ovulation is induced using fertility treatments that stimulate follicle development during the follicular phase?
• If neurons accumulate abnormal protein aggregates like amyloid plaques, which consequence relating to proteasomal degradation becomes significant?