Improved Afternoon Hepatic Glucose Disposal and Storage Requires Morning Engagement of Hepatic Insulin Receptors

Morning insulin delivery primes the liver for increased hepatic glucose uptake (HGU) later in the day, but until now, the mechanism (direct hepatic and/or indirect insulin action) remained unclear. This study compared insulin infusion via endogenous (hepatic portal vein) and clinical (peripheral) routes to assess their impact on afternoon hepatic glucose disposal. Arterial hyperinsulinemia in the morning, without a concomitant increase in insulin at the liver, failed to induce a significant enhancing effect on afternoon HGU and glycogen storage, unlike morning hepatic portal vein insulin delivery, which did. These findings highlight the importance of achieving appropriate hepatic insulin exposure in the morning to effectively prime the liver for enhanced glucose disposal later in the day.