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1 Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA; Unite de Nutrition et Metabolisme Proteique, INRA, Centre de Recherches en Nutrition Humaine de Clermont-Ferrand, Ceyrat, France
2 Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA; Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, TN, USA
3 Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
4 Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, TN, USA
* To whom correspondence should be addressed. E-mail: genie.moore{at}vanderbilt.edu.
Whether GLP-1 requires the hepatic portal vein to elicit its insulin secretion-independent effects
on glucose disposal in vivo was assessed in conscious dogs using tracer and arteriovenous
difference techniques. In study 1, 6 conscious overnight-fasted dogs underwent oral glucose
tolerance testing (OGTT) to determine target GLP-1 concentrations during clamp studies. Peak
arterial and portal values during OGTT ranged from 23 to 65 pM and from 46 to 113 pM,
respectively. In study 2, we conducted hyperinsulinemic-hyperglycemic clamp experiments
consisting of 3 periods (P1, P2, P3) during which somatostatin, glucagon, insulin and glucose
were infused. The control group (C) received saline, the PePe group received GLP-1 (1 pmol.kg-1..min-1) peripherally, the PePo group received GLP-1 (1 pmol.kg-1.min-1) peripherally (P2) then
intraportally (P3), and the PeHa group received GLP-1 (1 pmol.kg-1.min-1) peripherally (P2) and
then through the hepatic artery (P3) in order to increase the hepatic GLP-1 load to the same
extent as in P3 in PePo (n=8/group). Arterial GLP-1 levels increased similarly in all groups
during P2 (~50 pM) whereas portal GLP-1 levels were significantly increased (2-fold) in PePo vs
PePe and PeHa during P3. During P2, NHGU increased slightly but not significantly (vs P1) in
all groups. During P3, GLP-1 increased NHGU in the PePo and PeHa groups more than in C and
PePe (
10.8±1.3 and 10.6±1.0 vs 5.7±1.0 and 5.4±0.8 µmol.kg-1.min-1, respectively; P<0.05). In
conclusion, physiologic GLP-1 levels increase glucose disposal in the liver and this effect does
not involve GLP-1 receptors located in the portal vein.
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