Hepatic and extrahepatic splanchnic glucose metabolism in the postabsorptive and glucose fed dog

Eugene J. Barrett, Eleuterio Ferrannini, Richard Gusberg, Stefano Bevilacqua, Ralph A. DeFronzo

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

In awake dogs we measured the glucose balance across the liver and extrahepatic splanchnic tissues in the postabsorptive state and during two hours of IV infusion of glucose or for three hours following ingestion of oral glucose and during four hours of sequential intraportal followed by oral glucose. The IV glucose infusion rate was adjusted to maintain a steady state glucose concentration of either euglycemic levels (insulin clamp, group 1, N = 4), 125 mg 100 mL above the postabsorptive glucose concentration (+125 mg glucose clamp, group 2, N = 3) or 200 mg 100 mL above basal glucose levels (+200 mg glucose clamp, group 3, N = 7). Oral glucose was given at a dose of either 1.5 g/kg (group 4, N = 7) or 2.5 g/kg (group 5, N = 12). In dogs that received IV glucose, basal gut glucose uptake (0.5 ± 0.1 mg/min · kg) was stimulated by hyperglycemia (1.5 ± 0.5 and 1.4 ± 0.1 mg/min · kg for group 2 and 3, respectively, P < 0.05). In these same animals basal hepatic glucose output (-2.7 ± 0.3 mg/min · kg) was promptly suppressed and net hepatic glucose uptake occurred (2.8 ± 0.2 and 2.4 ± 0.5 mg/min · kg in group 2 and 3 respectively). Euglycemic hyperinsulinemia (group 1) suppressed postabsorptive hepatic glucose release but did not enhance glucose removal by either the liver or gut tissues. After oral glucose gut tissues released absorbed glucose into portal blood. Over three hours following the glucose meal 74% and 59% of the ingested glucose was absorbed in group 4 and 5, respectively. As with IV glucose, postabsorptive hepatic glucose production was suppressed and over the first two hours after feeding the liver took up glucose (3.4 ± 1.0 and 3.1 ± 0.7 mg/min · kg groups 4 and 5, respectively) at a rate similar to that seen with IV glucose. To further examine the effect of the route of glucose administration on liver glucose handling, hepatic glucose balance was measured serially over four hours in three dogs that received IV glucose into a mesenteric vein to produce portal hyperglycemia (+125 mg/dL portal glucose clamp N = 3). Oral glucose (2.5 mg/kg) was given at two hours, and the rate of the mesenteric glucose infusion adjusted to maintain portal glycemia constant. The hepatic glucose balance averaged 5.5 mg/min · kg over the 0 to 2 hour period and 4.2 ± 1.0 mg/min · kg over the 2 to 4 hour time. We conclude that in the dog: (1) hyperinsulinemia alone suppresses liver glucose production but doss not significantly stimulate gut or liver glucose removal, (2) combined hyperglycemia and hyperinsulinemia stimulate gut and liver glucose uptake, and (3) the liver removes orally and intraportally and peripheral intravenously administered glucose at similar rates.

Original languageEnglish (US)
Pages (from-to)410-420
Number of pages11
JournalMetabolism
Volume34
Issue number5
DOIs
StatePublished - May 1985
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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