Our data suggest that large vessels may adapt to sustained hyperglycemia/hyperosmolarity and developed a compensative way through upregulating eNOS/HO for vasodilation, while the clustering risk factors including marked obesity, hyperinsulinemia, and hypertriglyceridemia other than hyperglycemia are involved in vessel dysfunction of the obese OLETF. The gene discussed is HMOX1; the disease is hyperinsulinism.