Pancreatic response to mild non-insulin-induced hypoglycemia does not involve extrinsic neural input

Mild non-insulin-induced hypoglycemia achieved by administration of a glyco gen phosphorylase inhibitor results in increased glucagon and decreased ins ulin secretion in conscious dogs. Our aim was to determine whether the resp onse of the endocrine pancreas to this mild hypoglycemia can occur in the a bsence of neural input to the pancreas. Seven dogs underwent surgical pancr eatic denervation (PDN [study group]), and seven dogs underwent sham denerv ation (control [CON] group). Each study consisted of a 100-min equilibratio n period, a 40-min control period, and a 180-min test period. At the start of the test period, Bay R3401 (10 mg/kg), a glycogen phosphorylase inhibito r, was administered orally. Arterial plasma glucose (mmol/l) fell to a simi lar minimum in CON (5.0 +/- 0.1) and PDN (4.9 +/- 0.3). Arterial plasma ins ulin also fell to similar minima in both groups (CON, 20 +/- 6 pmol/l; PDN, 14 +/- 5 pmol/l). Arterial plasma glucagon rose to a similar maximum in CO N (73 +/- 8 ng/l) and PDN (72 +/- 9 ng/l). Insulin and glucagon secretion d ata support these plasma hormone results, and there were no significant dif ferences in the responses in CON and PDN for any parameter. Pancreatic nore pinephrine content in PDN was only 4% of that in CON, confirming successful sympathetic denervation. Pancreatic polypeptide levels tended to increase in CON and decrease in PDN in response to mild hypoglycemia, indicative of parasympathetic denervation. It thus can be concluded that the responses of alpha- and beta -cells to mild non-insulin-induced hypoglycemia can occur in the absence of extrinsic neural input.