The Role of Efferent Cholinergic Transmission for the Insulinotropic and Glucagonostatic Effects of XXXX .

@entity1 @entity4053 @entity3897 @entity6757 @entity413
UNASSIGNED: The importance of vagal efferent signaling for the insulinotropic and glucagonostatic effects of @entity6757 was investigated in a randomized single-blinded study. Healthy male @entity1 (n=10) received @entity3897 to block vagal cholinergic transmission or saline infusions on separate occasions. At t=15min, plasma @entity413 was clamped at 6mmol/L. @entity6757 was infused at a low dose (0.3pmol/kg/min) from t = 45-95min and at a higher dose(1 pmol/kg/min) from t = 95-145 min. @entity3897 blocked muscarinic, cholinergic transmission, as evidenced by an increase in heart rate (peak: 70  2(saline) vs. 90  2( @entity3897 ) beats/min, P<0.002) and suppression of pancreatic polypeptide levels (area under the curve during the @entity6757 infusions (AUC45-145): 492  85(saline) vs. 247  59( @entity3897 ) pmol/L*min,P<0.0001). More @entity413 was needed to maintain the clamp during the high-dose @entity6757 infusion steady state period on the @entity3897 day (6.4  0.9(saline) vs. 8.7  0.8( @entity3897 ) mg/kg/min,P<0.0023). @entity6757 dose-dependently increased insulin secretion on both days. The insulinotropic effect of @entity6757 was not impaired by @entity3897 (C-peptide AUCs45-145: 99  8(saline) vs. 113  13( @entity3897 ) nmol/L*min,P=0.19). @entity3897 suppressed glucagon levels additively with @entity6757 (AUC45-145:469  70(saline) vs. 265  50( @entity3897 ) pmol/L*min,P=0.018) - resulting in @entity4053 when infusions were suspended (3.6  0.2(saline) vs. 2.7  0.2( @entity3897 ) mmol/L, P<0.0001). To ascertain whether @entity3897 could independently suppress glucagon levels, control experiments (n=5) were carried out without @entity6757 infusions (AUC45-145: 558  103(saline) vs. 382  76( @entity3897 ) pmol/L*min,P=0.06). Our results suggest that efferent muscarinic activity is not required for the insulinotropic effect of exogenous @entity6757 but that blocking efferent muscarinic activity independently suppresses glucagon secretion. In combination, @entity6757 and muscarinic blockade strongly affects @entity413 turnover.
