INS and hyperinsulinism: Homozygous db/db mice developed an impairment in insulin sensitivity as indicated by Insulin tolerance test (ITT), glucose tolerance test (GTT) (p<0.05 vs non-irisin treatment), hyperglycemia (p<0.05 vs heterozygous control), and hyperinsulinemia (serum insulin: 0.81 ± 0.065 ng/ml in heterozygous control vs. 8.33 ± 0.69 ng/ml in homozygous db/db control, p<0.0001), which were attenuated by the administration of irisin (serum insulin 8.32 ± 0.68 ng/ml in homozygous db/db control vs 6.56 ± 0.38 ng/ml in homozygous db/db irisin treatment, p<0.0001).