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Nutrient Metabolism

Portal Vein Caffeine Infusion Enhances Net Hepatic Glucose Uptake during a Glucose Load in Conscious Dogs^1,2

R. Richard Pencek^*,3, Danielle Battram, Jane Shearer^*, Freyja D. James^*, D. Brooks Lacy, Kareem Jabbour^**, Phillip E. Williams^**, Terry E. Graham and David H. Wasserman^*,

^* Department of Molecular Physiology and Biophysics, Diabetes Research and Training Center, and ^** Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, and Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1

³To whom correspondence should be addressed. E-mail: r.r.pencek{at}vanderbilt.edu.

We determined whether intraportal caffeine infusion, at rates designed to create concentrations similar to that seen with normal dietary intake, would enhance net hepatic glucose uptake (NHGU) during a glucose load. Dogs (n = 15) were implanted with sampling and infusion catheters as well as flow probes >16 d before the studies. After a basal sampling period, dogs were administered a somatostatin infusion (0–150 min) as well as intraportal infusions of glucose [18 µmol/(kg · min)], basal glucagon [0.5 ng/(kg · min)], and insulin [8.3 pmol/(kg · min)] to establish mild hyperinsulinemia. Arterial glucose was clamped at 10 mmol/L with a peripheral glucose infusion. At 80 min, either saline (Control; n = 7) or caffeine [1.5 µmol/(kg · min); n = 8] was infused into the portal vein. Arterial insulin, glucagon, norepinephrine, and glucose did not differ between groups. In dogs infused with caffeine, NHGU was significantly higher than in controls [21.2 ± 4.3 vs. 11.2 ± 1.6 µmol/(kg · min)]. Caffeine increased net hepatic lactate output compared with controls [12.5 ± 3.8 vs. 5.5 ± 1.5 µmol/(kg · min)]. These findings indicate that physiologic circulating levels of caffeine can enhance NHGU during a glucose load, and the added glucose consumed by the liver is in part converted to lactate.

KEY WORDS: • glycogen • coffee • carbohydrate • methylxanthines

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