ANGPTL8 and hyperinsulinism: Thus, even though hyperinsulinemia during euglycemic clamp has been shown to acutely suppress plasma ANGPTL3 concentrations in obese non-diabetic patients, prolonged hyperinsulinemia increases the ANGPTL8 RNA and protein concentrations in cell cultures of hepatocytes and adipocytes [26]; because the secretion of ANGPTL3 and ANGPTL8 is mechanistically interdependent [27], it is possible that the stimulation of ANGPTL8 production by chronic hyperinsulinemia might result in the concurrent increase in circulating ANGPTL3 [3].