We observed that a 4-h morning (AM) duodenal infusion of
glucose versus saline doubled hepatic
glucose uptake (HGU) and storage during a hyperinsulinemic-hyperglycemic (HIHG) clamp that afternoon (PM). To separate the effects of AM
hyperglycemia versus AM
hyperinsulinemia on the PM response, we used hepatic balance and tracer ([3-3H]
glucose) techniques in conscious dogs. From 0 to 240 min, dogs underwent a euinsulinemic-hyperglycemic (GLC; n = 7) or hyperinsulinemic-euglycemic (INS; n = 8) clamp. Tracer equilibration and basal sampling occurred from 240 to 360 min, followed by an HIHG clamp (360-600 min; four times basal
insulin, two times basal glycemia) with portal
glucose infusion (4 mg ⋅ kg-1 ⋅ min-1). In the HIHG clamp, HGU (5.8 ± 0.9 vs. 3.3 ± 0.3 mg ⋅ kg-1 ⋅ min-1) and net
glycogen storage (6.0 ± 0.8 vs. 2.9 ± 0.5 mg ⋅ kg-1 ⋅ min-1) were approximately twofold greater in INS than in GLC. PM
hepatic glycogen content (1.9 ± 0.2 vs. 1.3 ± 0.2 g/kg
body weight) and
glycogen synthase (GS) activity were also greater in INS versus GLC, whereas
glycogen phosphorylase (GP) activity was reduced. Thus AM
hyperinsulinemia, but not AM
hyperglycemia, enhanced the HGU response to a PM HIHG clamp by augmenting GS and reducing GP activity. AM
hyperinsulinemia can prime the liver to extract and store
glucose more effectively during subsequent same-day meals, potentially providing a tool to improve
glucose control.