CYP3A4 and Hyperglycemia: We observed for the first time that PHHs in MPCCs: a) maintain albumin and urea secretions at similar levels across all glycemic states; b) significantly upregulate CYP3A4 activity under hypoglycemia; and, c) accumulate neutral lipids while becoming less sensitive to insulin-mediated reduction in glucose output under hyperglycemia as compared to a normoglycemic control.