alpha- and beta-cell responses to small changes in plasma glucose in the conscious dog

The responses of the pancreatic alpha- and beta -cells to small changes in glucose were examined in overnight-fasted conscious dogs. Each study consis ted 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 p hosphorylase inhibitor, was administered orally, either alone to create mil d hypoglycemia or with peripheral glucose infusion to maintain euglycemia o r 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 mu mol . k(-1) . min(-1) by 30 and 90 min. As a re sult, 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 differ ence 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 g lucagon levels and the hepatic portal-arterial difference in plasma glucago n increased from 43 +/- 5 and 4 +/- 2 to 51 +/- 5 and 10 +/- 5 ng/l by 30 m in (P < 0.05) and to 79 +/- 16 and 31 +/- 15 ng/l by 90 min (P < 0.05), res pectively. In euglycemic dogs, the arterial plasma glucose level remained a t 5.9 +/- 0.1 mmol/l, and the NHGO decreased from 10 +/- 0.6 to -3.3 +/- 0. 6 mu mol . 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 mu mo l . 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 plasm a 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 alpha- and beta -cells of the pancreas respond as a coupled unit to very small decreases in the plasma glucose level.