F1 cross between 129 and B6 with the Akita mutation and Nos3 KO. Mice homozygous for the Nos3 targeted mutation are viable and fertile. They have elevated blood pressure that is about 20 mmHg higher than that seen in normal wildtype siblings. They also show a decreased heart rate. Female homozygotes are smaller in body weight than normal wildtype siblings. Hyperglycemic-euglycemic clamp studies demonstrate that homozygotes exhibit insulin resistance at the level of the liver and peripheral tissues.