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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 9 3093-3098
Copyright © 1997 by The Endocrine Society

Original Studies

Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Insulin and Glucagon Secretion in Humans1

K. Filipsson, K. Tornøe, J. Holst and B. Ahrén

Department of Medicine, Lund University (K.F., B.A.), Malmö, Sweden; and the Department of Endocrinology and Metabolism, Panum Institute (K.T., J.H.), Copenhagen, Denmark

Address all correspondence and requests for reprints to: Dr. Karin Filipsson, Wallenberg Lab, Floor 2, Department of Medicine, Malmö University Hospital, S-205 02 Malmö, Sweden. E-mail: Karin.Filipsson{at}medforsk.mas.lu.se

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been localized to pancreatic nerves and demonstrated to stimulate insulin and glucagon secretion in experimental animals. This study examined the occurrence and possible function of PACAP in the human pancreas. The content of PACAP27 was 0.44 ± 0.04 pmol/g tissue, and that of PACAP38 was 29.6 ± 6.4 pmol/g tissue in extracted human pancreas (n = 4). Furthermore, in a homogeneous group of seven healthy postmenopausal women, all aged 57 yr, iv infusion of synthetic human PACAP27 (3 pmol/kg·min for 75 min) increased basal levels of insulin, C peptide, and glucagon without significantly influencing basal glucose after 14 min. At 15 min, glucose was administered rapidly (0.3 g/kg, iv). The peak insulin after bolus glucose was 797 ± 232 pmol/L during PACAP27 infusion vs. 559 ± 164 pmol/L during saline infusion (P = 0.018). Also, the peak in C peptide after glucose was potentiated by PACAP27 (P = 0.018). In contrast, hepatic extraction, calculated as the C peptide/insulin molar ratio, was not significantly affected by PACAP27, and neither the glucose elimination rate nor reduction of serum insulin after the glucose-induced peak was changed by PACAP27. We conclude that PACAP occurs in human pancreas and stimulates insulin and glucagon secretion in humans. This suggests that PACAP is involved in the regulation of islet function in humans.




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