Defective insulin secretion during total parenteral nutrition in rat and its normalization by pituitary adenylate cyclase-activating polypeptide 27.
The role of PACAP27, PACAP38 and VIP in the regulation of insulin release from pancreatic islets isolated from rats previously subjected to total parenteral nutrition (TPN) for 10 days was studied. Glucose-stimulated insulin secretion from islets of TPN rats was attenuated in parallel with cyclic AMP production. Immunocytochemistry showed an increased number of VIP-immunoreactive nerve fibers in the pancreatic islets of TPN rats. PACAP27, PACAP38 and VIP dose dependently and to the same magnitude potentiated insulin secretion from the islets of freely fed controls in the presence of a substimulatory glucose concentration (8.3 mmol/l). The secretory response of islets from TPN-treated rats to these neuropeptides was, however, markedly exaggerated compared to the controls. The insulin response of islets from TPN-treated rats to PACAP27 and PACAP38 was much greater than to VIP. With respect to insulin secretion, TPN treatment shifted the PACAP27 and PACAP38 dose-response curve to the left by two orders of magnitude. In the presence of 8.3 mmol/l glucose, cAMP accumulation was slightly higher in islets from TPN rats and the PACAP27, PACAP38 and VIP-stimulated increase in the cAMP production was markedly greater compared to the controls. Additional complementary in vivo experiments showed that PACAP27 normalized the defective glucose-stimulated insulin secretory response of TPN-treated rats. The data suggest that the defective nutrient-stimulated insulin secretion seen after long-term TPN treatment could be normalized by agents stimulating cAMP production possibly through cAMP/PK A-pathway.
Salehi
Albert
A
Department of Physiological Sciences, Division of Pharmacology, University of Lund, BMC F13, S-221 84 Lund, Sweden. Salehi@farm.lu.se
Qader
Saleem S
SS
Ekblad
Eva
E
Ekelund
Mats
M
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism / Q000502:physiology*; D010288:Parenteral Nutrition; D010455:Peptides / Q000737:chemistry; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
C495403:Adcyap1 protein, rat; D007328:Insulin; D009479:Neuropeptides; D010455:Peptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose