AM Insulinization of the Liver Is an Important Driver of PM Hepatic Glucose Uptake

• Published in: Physiology (Bethesda, Md.) Md.), 2024-05, Vol.39 (S1)
• Main Authors: Waterman, Hannah, Moore, Mary, Smith, Marta, Farmer, Ben, Yankey, Kalisha, Kraft, Guillaume, Scott, Melanie
• Format: Article
• Language: English
• ISSN: 1548-9213; 1548-9221
• DOI: 10.1152/physiol.2024.39.S1.470

Abstract only Glucose tolerance is significantly improved in response to consuming a second, identical meal later in the day. It is known that physiologic (portal vein) exposure to insulin in the morning primes the liver for increased hepatic glucose uptake and glycogen storage in the afternoon. Although this phenomenon has been observed in both healthy and diabetic individuals, it has not yet been established whether or not morning peripheral insulin delivery could bring about the same response. Thus, the aim of this study was to determine how the route of morning insulin delivery impacts the liver’s ability to extract and store glucose later in the day. To explore this aim, we delivered insulin into the portal vein (Po Ins) or a leg vein (Pe Ins) in the morning (AM) and subsequently challenged conscious dogs to a hyperinsulinemic-hyperglycemic (HIHG) clamp in the afternoon (PM). We then assessed the impact that each route of AM insulin delivery had on hepatic glucose uptake (HGU), non-HGU, and glycogen storage in the PM. The insulin infusion rates used in the Po Ins group were selected to mimic the rise in endogenous insulin secretion previously observed during a 4hr AM duodenal glucose infusion (2.1 mU/kg/min [0-30 min], 2.4 mU/kg/min [30-60 min], and 1.5 mU/kg/min [60-240 min]). In efforts to expose both groups to the same amount of insulin in the periphery while creating a difference at the liver, these rates were halved in the Pe Ins group. In the PM clamp, all groups received 4x basal insulin, 2x basal glycemia, and portal glucose infusion to simulate a second meal. During the 2.5hr PM clamp, the mean HGU was 1.8-fold higher in the Po Ins group vs. the Pe Ins group (HGU of 6.28±0.62 vs. 3.49±0.31 mg/kg/min; net AUC of 827±82 vs. 474±40 mg/kg/2.5hr, p