PLN and Hyperinsulinemia: For example, in rats fed a high sucrose diet that induced a pre-T2D phenotype (hyperinsulinemia, mild hyperglycemia, and hyperlipidemia) with diastolic dysfunction, a reduction in SR calcium reuptake by ~30% was observed along with significant reductions in both PKA and CaMKII mediated phosphorylation of PLN, yet no changes were observed in total PLN or SERCA2a protein levels, suggesting the decreased SERCA2a activity was driven by upstream alterations in PLN phosphorylation [57].