The Ang/Tie angiogenic cascade also participated in the adaptive increase in islet vascularization with Ang-2 upregulation early during high fat/ high sucrose feeding in mice (compensatory phase- cartoon Fig 5) and a persistent Tie receptor upregulation through 24 weeks of the diabetogenic diet, together with upregulated vessel markers eNOS and CD31 at 24 weeks on a high fat diet and ICAM-1 also in human T2D islets. This evidence concerns the gene NOS3 and type 2 diabetes mellitus.