Morning Hyperinsulinemia Primes the Liver for Glucose Uptake and Glycogen Storage Later in the Day

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- 3 H]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.