There was an 8- to 10-fold decrease in the Serca2 concentration in islets from db/db mice compared to that in the controls26,45 and an approximately 70% decrease in the expression of Serca2b in islets from insulin receptor substrate-1 knockout (IRS-1 KO) mice, which exhibited defective GSIS, mild insulin resistance, and reduced insulin synthesis46. The gene discussed is IRS1; the disease is Insulin resistance.