Effect of insulin-induced hypoglycaemia on plasma pancreatic polypeptide and glucagon levels in conscious dogs

ABSTRACT

The aim of the present study has been to identify the role of nitric oxide [NO] in mediating pancreatic endocrine responses to severe hypoglycaemia [2.0 nmol/kg insulin I.V.] in conscious dogs. The experiments were carried out on 18 apparently healthy adult male conscious dogs divided into three groups Group I Six dogs sacrificed as control group. Group II Six dogs subjected to severe hypoglycaemia in the absence of L-NAME [NOS blocker] and sodium nitroprusside [NO donor]. Group III Six dogs subjected to severe hypoglycaemia in the presence of L-NAME [100 mg/kg I.A.] and sodium nitroprusside [2-4 micro g/min/kg I.V.].Glucose was measured by means of a Mark 2 Beckman Glucose Analyser, Glucagon and PP were easured by radioimmunoassay. Determination of cGMP levels was studied using pancreatic tissues from the three studied groups. Administration of L-NAME effectively produced a significantly reduced plasma pancreatic polypeptide [PP] response. In contrast, the glucagon response was not significantly affected. Moreover, plasma glucagon values were consistently higher in group III [with L- NAME] when compared to group II [without L-NAME] at 30 and 120 min. intervals, [t = 5.36, P < 0.001, and t = 6.32, P< 0.001 respectively]. One can conclude that, in the absence of L-NAME, production of NO may contribute to the PP response, but not to the glucagon response to hypoglycaemia in this species under physiological conditions, in this study, there was a significant increase in pancreatic tissue cGMP in the studied dogs without L-NAME and sodium nitroprusside as compared to both control dogs [t= 11.6, P < 0.001], and those receiving L-NAME and sodium nitroprusside [t = 8.25, P < 0.05]. This explains a possible rote of cGMP in the process of PP release through NO gas. Conclusions. Administration of NOS blocker has produced a significantly reduced plasma pancreatic polypeptide [PP] response with no significant effect on glucagon secretion during insulin-induced severe hypoglycaemia in conscious dogs. cGMP has been found to play a possible role in the process of PP release through NO gas