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© 2001 by the American Diabetes Association, Inc.
- and ß-Cell Responses to Small Changes in Plasma Glucose in the Conscious Dog
From the Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Address correspondence and reprint requests to Masakazu Shiota, DVM, PhD, Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 710 Medical Research Bldg. 1, Nashville, TN 37232. E-mail: masakazu.shiota{at}mcmail.vanderbilt.edu .
The responses of the pancreatic 
- and ß-cells to small changes
in glucose were examined in overnight-fasted conscious dogs. Each study
consisted of an equilibration (-140 to -40 min), a control (-40 to 0 min), and
a test period (0 to 180 min), during which BAY R3401 (10 mg/kg), a glycogen
phosphorylase inhibitor, was administered orally, either alone to create mild
hypoglycemia or with peripheral glucose infusion to maintain euglycemia or
create mild hyperglycemia. Drug administration in the hypoglycemic group
decreased net hepatic glucose output (NHGO) from 8.9 ± 1.7 (basal) to
6.0 ± 1.7 and 5.8 ± 1.0 µmol · kg-1
· min-1 by 30 and 90 min. As a result, the arterial plasma
glucose level decreased from 5.8 ± 0.2 (basal) to 5.2 ± 0.3 and
4.4 ± 0.3 mmol/l by 30 and 90 min, respectively (P < 0.01).
Arterial plasma insulin levels and the hepatic portal-arterial difference in
plasma insulin decreased (P < 0.01) from 78 ± 18 and 90
± 24 to 24 ± 6 and 12 ± 12 pmol/l over the first 30 min
of the test period and decreased to 18 ± 6 and 0 pmol/l by 90 min,
respectively. The arterial glucagon levels and the hepatic portal-arterial
difference in plasma glucagon increased from 43 ± 5 and 4 ± 2 to
51 ± 5 and 10 ± 5 ng/l by 30 min (P < 0.05) and to
79 ± 16 and 31 ± 15 ng/l by 90 min (P < 0.05),
respectively. In euglycemic dogs, the arterial plasma glucose level remained
at 5.9 ± 0.1 mmol/l, and the NHGO decreased from 10 ± 0.6 to
-3.3 ± 0.6 µmol · kg-1 · min-1
(180 min). The insulin and glucagon levels and the hepatic portal-arterial
differences remained constant. In hyperglycemic dogs, the arterial plasma
glucose level increased from 5.9 ± 0.2 to 6.2 ± 0.2 mmol/l by 30
min, and the NHGO decreased from 10 ± 1.7 to 0 µmol ·
kg-1 · min-1 by 30 min. The arterial plasma
insulin levels and the hepatic portal-arterial difference in plasma insulin
increased from 60 ± 18 and 78 ± 24 to 126 ± 30 and 192
± 42 pmol/l by 30 min, after which they averaged 138 ± 24 and
282 ± 30 pmol/l, respectively. The arterial plasma glucagon levels and
the hepatic portal-arterial difference in plasma glucagon decreased slightly
from 41 ± 7 and 4 ± 3 to 34 ± 7 and 3 ± 2 ng/l
during the test period. These data show that the - and ß-cells of
the pancreas respond as a coupled unit to very small decreases in the plasma
glucose level.
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