The second meal phenomenon refers to the improvement in glucose tolerance seen following a second identical meal. We previously showed that 4 hours of morning (AM) hyperinsulinemia, but not hyperglycemia, enhanced hepatic glucose uptake (HGU) and glycogen storage during an afternoon (PM) hyperinsulinemic hyperglycemic clamp (HIHG). Our current aim was to determine if the duration or pattern of morning hyperinsulinemia is important for the PM response to a HIHG clamp. To determine this, we administered the same total amount of insulin either over 2h in the first half of the morning (Ins2h-A), over 2h in the 2nd half of the morning (Ins2h-B), or over the entire 4h (Ins4h) of the morning. In the 4h PM period, all three groups had 4x basal insulin, 2x basal glycemia, and portal glucose infusion to simulate a meal. During the PM clamp, there was a marked increase in the mean hepatic glucose uptake and hepatic glycogen synthesis in the Ins4h group compared to the Ins2h-A and Ins2h-B groups, despite matched hepatic glucose and insulin loads. Thus, the longer duration (Ins4h) of mild hyperinsulinemia in the morning seems to be the key to much greater liver glucose uptake during the PM clamp.