Priming Effect of a Morning Meal on Hepatic Glucose Disposition Later in the Day

Abstract

We used hepatic balance and tracer ([3H]glucose) techniques to examine the impact of “breakfast” on hepatic glucose metabolism later in the same day. From 0–240 min, 2 groups of conscious dogs (n = 9 dogs/group) received a duodenal infusion of glucose (GLC) or saline (SAL), then were fasted from 240–360 min. Three dogs from each group were euthanized and tissue collected at 360 min. From 360–600 min, the remaining dogs underwent a hyperinsulinemic (4× basal) hyperglycemic clamp (arterial blood glucose 146 ± 2 mg/dL) with portal GLC infusion. The total GLC infusion rate was 14% greater in dogs infused with GLC than in those receiving SAL (AUC360–600min 2,979 ± 296 vs. 2,597 ± 277 mg/kg, respectively). The rates of hepatic glucose uptake (5.8 ± 0.8 vs. 3.2 ± 0.3 mg ⋅ kg−1 ⋅ min−1) and glycogen storage (4.7 ± 0.6 vs. 2.9 ± 0.3 mg ⋅ kg−1 ⋅ min−1) during the clamp were markedly greater in dogs receiving GLC compared with those receiving SAL. Hepatic glycogen content was ∼50% greater, glycogen synthase activity was ∼50% greater, glycogen phosphorylase activity was ∼50% lower, and the amount of phosphorylated glycogen synthase was 34% lower, indicating activation of the enzyme, in dogs receiving GLC compared with those receiving SAL. Thus, morning GLC primed the liver to extract and store more glucose in the presence of hyperinsulinemic hyperglycemia later in the same day, indicating that breakfast enhances the liver’s role in glucose disposal in subsequent same-day meals.

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

“…At that point, glucose infusions ceased, and the portal and hepatic sampling catheters and blood flow probes were exteriorized under local anesthesia. In all respects, the last 6 h of the study (the nonclamp period and clamp 2) were identical in the GLC and INS groups as well as with the groups contained in our previous report (6).…”

“…In the GLC group, regular insulin (Novolin R; Novo Nordisk, Bagsvaerd, Denmark) was infused into the splenic and jejunal vein catheters at a basal rate (0.3 mU $ kg 21 $ min 21 ) throughout the 4 h AM clamp, and 20% dextrose (Baxter, Deerfield, IL) was infused intraportally via the splenic and jejunal catheters. The infusion rate was adjusted as necessary to raise the arterial blood glucose level from 77 to 120 mg/dL (to reproduce the glucose excursion observed in our previous study [6]). In the INS group, regular insulin was infused intraportally at 2.1 mU $ kg 21 $ min 21 from 0 to 30 min, 2.4 mU $ kg 21 $ min 21 from 30 to 60 min, and 1.5 mU $ kg 21 $ min 21 from 60 to 240 min.…”

“…After a 90-min equilibration period, nonclamp period blood samples were collected from the sampling catheters between 330 and 360 min. At the end of the nonclamp period, two INS and two GLC dogs were anesthetized, and hepatic tissue was rapidly collected from each of three liver lobes, freeze clamped, and stored at 280°C, as previously described (6). These four dogs were euthanized at the end of the tissue collection and are referred to as the amINS and amGLC dogs.…”

“…Increased muscle glucose uptake (4) and, conversely, increased hepatic glucose disposal (1) have been reported in response to the second meal. We recently demonstrated in conscious dogs that a 4-h duodenal glucose infusion in the morning (AM), compared with an AM duodenal saline infusion, stimulated hepatic glucose uptake (HGU) and glycogen storage during a hyperinsulinemichyperglycemic (HIHG) clamp, mimicking a meal response, later in the same day (6). In contrast to our findings in regard to the liver, there was no difference between groups in nonhepatic (primarily muscle) glucose disposal during the afternoon (PM) clamp (6).…”

“…We recently demonstrated in conscious dogs that a 4-h duodenal glucose infusion in the morning (AM), compared with an AM duodenal saline infusion, stimulated hepatic glucose uptake (HGU) and glycogen storage during a hyperinsulinemichyperglycemic (HIHG) clamp, mimicking a meal response, later in the same day (6). In contrast to our findings in regard to the liver, there was no difference between groups in nonhepatic (primarily muscle) glucose disposal during the afternoon (PM) clamp (6). Use of clamp conditions allowed us to control the PM pancreatic hormone and glucose levels so that we could quantify organ glucose disposal in response to the "second meal" without the complicating factors of varying concentrations of insulin, glucagon, and glucose.…”