SIK2 and Hyperinsulinemia: Nevertheless, Sik2 KO mice showed abnormalities of hyperglycemia and hypertriglyceridemia, which are related to the glucose absorption and insulin tolerance, increased leukocytes lipolysis, and decreased fatty acid intake in peripheral tissues.110 Liver specific Sik2 KO mice (Sik2fl/fl;Cre+/−) displayed normal glycemia.33 However, Sik3 KO mice derived from Sik3 KO embryonic stem (ES) cells exhibited a dystrophic phenotype, including lipodystrophy, hypolipidemia, hypoglycemia, and hyperinsulinemia, with the phenomena of cholestasis and cholelithiasis.