Intraperitoneal PACAP administration decreases blood glucose in GK rats, and in normal and high fat diet mice.

PACAP is an islet peptide that serves as an endogenous amplifier of glucose induced insulin secretion. Furthermore, we has recently found that PACAP also potentiates insulin stimulated glucose uptake in adipocytes. Therefore, an antidiabetic action of PACAP is possible. In the present study, we examined the effect of PACAP treatment of the hyperglycemia in GK rats, an animal model of type 2 diabetes, and in high fat fed C47BL/6J mice, an animal model for glucose intolerance. GK rats housed with normal diet exhibited a normal level of blood glucose until three weeks old but significant hyperglycemia at eight weeks. When GK rats were treated with daily PACAP38 (i.p. injection, 6 pmol/kg) from age three weeks, development of hyperglycemia was prevented. In high fat fed mice, i.p. administration of PACAP27 for five (25 nmol/kg twice daily) reduced plasma glucose levels to 6.9 +/- 0.2 mmol/l compared to 8.1 +/- 0.2 mmol/l in saline injected animals (p < 0.001) without altering baseline insulin levels. We conclude that PACAP reduces circulating glucose in animal models of type 2 diabetes and glucose intolerance. The mechanism of this action needs to be established.