Impairment of insulin secretion in pancreatic islets isolated from Walker 256 tumor-bearing rats

• Published in: The American journal of physiology Vol. 271; no. 3 Pt 1; p. C804
• Main Authors: el Razi Neto, S, Zorn, T M, Curi, R, Carpinelli, A R
• Format: Journal Article
• Language: English
• Published: United States 01.09.1996
• Subjects: Animals; Calcium Radioisotopes; Carcinoma 256, Walker - metabolism; Carcinoma 256, Walker - pathology; Insulin - metabolism; Insulin Secretion; Ion Transport; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Male; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Rats; Rubidium Radioisotopes
• ISSN: 0002-9513
• DOI: 10.1152/ajpcell.1996.271.3.c804

Previous study has shown that insulin secretion in response to a glucose stimulus (16.7 mM) is reduced in islets isolated from Walker 256 tumor-bearing rats compared with controls. The ultrastructure, 45Ca2+ and 86Rb+ fractional outflow rate, phosphoinositide hydrolysis, and [U-14C]glucose decarboxylation were examined in islets isolated from tumor-bearing and control rats. The general morphological features of the islets from the control and experimental groups were very similar. The 86Rb+ fractional outflow rate was not changed, whereas the 45Ca2+ fractional outflow rate, [U-14C]glucose decarboxylation, and phosphoinositide metabolism were markedly reduced in islets from tumor-bearing rats. The changes in 45Ca2+ fractional outflow rate in islets from tumor-bearing rats were not due to impaired functioning of voltage-dependent calcium channels. By perifusing the islets in the presence of high potassium concentration, evidence was obtained that phospholipase C from islets from tumor-bearing rats reduced response to calcium. To further examine the mechanism involved in the impairment of insulin secretion by islets from tumor-bearing rats, islets isolated from normal rats were perifused after preincubation in the presence of serum from tumor-bearing rats. The results suggest that a thermolabile circulating factor is partially responsible for the changes described in islets isolated from Walker 256 tumor-bearing rats.