Type II Diabetes

High fat diet > Altered glucose transport (GLUT-2) into beta cells > v insulin secretion
Altered cholesterol transport (Abca1) into beta cells > v insulin secretion
v pro-insulin -> insulin in beta cells
?v amylin secretion > accumulation of islet amyloid polypeptide (amylin) > v glucose uptake in beta cells > v insulin secretion
Various genes related to pancreatic growth, development and insulin secretion
Glucokinase mutation > v phosphorylation of glucose > v glucose-6-P > v insulin secretion (MODY2)
Insulin promotor factor-1 mutation > v insulin binding > v insulin secretion (MODY4)

Genetic predisposition to v glucose metabolism & v glycogen storage (glycogen synthase) & v fatty acid metabolism (post-receptor defects)
Hypersecretion insulin (initially) > weight gain > chronic hyperglyceamia > v insulin secretion (vicious cycle)
'Adipokines' from adipocytes > insulin resistance
FFA > v glucose uptake
Insulin-receptor mutations (rare)
?Beta-3 adrenergic receptor mutation
?Peroxisome-proliferator-activated receptor (PPAR) mutation > ^ adipose tissue, v insulin sensitivity

v Leptin (or resistance) - ^ fat deposition (loss of hypothalamic endocrine control), v islet cell growth & pancreatic response to ^glucose > v insulin secretion
^ obesity, hyperglycaemia -> v Adiponectin - > ^adipocyte TNFa -> ^ insulin resistance,
^ chemokines -> v muscle glucose uptake

^ resistin -> ^ glucose production
^ plasminogen activator inhibitor -> ?
^ retinol-binding protein 4 ->
^ serum glucose > ^ Interleukin-1 beta islet cell secretion > ?beta cell dysfunction
^ uncoupling protein 2 -> v insulin secretion
v Obestatin