A selective immune attack
Beta cells carry antigens that the immune system mistakenly treats as foreign. Antigen-presenting cells activate autoreactive CD4+ T cells, which help CD8+ cytotoxic T cells recognize beta-cell peptides on MHC class I and kill the cells. Cytokines such as interferon-gamma, tumor necrosis factor, and interleukin-1 amplify the damage and impair surviving beta cells. Alpha cells and other islet cells are largely spared, so the loss is specific to insulin secretion.
Absolute, not relative, deficiency
The defect is loss of insulin production, not loss of insulin responsiveness. The receptor, IRS, PI3K/Akt cascade, AS160, and GLUT4 machinery you studied earlier remain structurally intact, but they are never activated because the ligand is absent. No amount of target-cell sensitivity can compensate for a hormone that is not secreted.
Glucagon without a counterweight
Alpha cells keep secreting glucagon. Normally insulin restrains glucagon release and opposes its hepatic effects; with insulin gone, glucagon signaling is unopposed. The fed-state switch that insulin normally throws is stuck in the fasted position, so the liver behaves as though the body is starving even when glucose is abundant in the blood.
Why symptoms appear late
Beta-cell loss is gradual. Clinical hyperglycemia usually appears only after a large fraction of beta-cell mass has been destroyed, which is why the disease can be immunologically active for years before it is diagnosed.