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For instance, NKCC1 βKO mice gradually became overweight, hyperinsulinemic, hyperglycemic, hypertriglyceridemic, glucose intolerant and insulin resistant while developing mild non-alcoholic steatohepatitis and reduced β-cell mass and function, i.e., typical conditions found in MetS ( βKO mice remain unresolved, it is evident that fundamental deficiencies in β-cell function and/or mass are pivotal in the development/progression of age-dependent metabolic dysregulation (Hudish et al., 2019)