Impairment of insulin secretion in pancreatic islets isolated from Walker 256 tumor-bearing rats.
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.
el Razi Neto
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Department of Physiology and Biophysics, University of Sao Paulo, Brazil.
Zorn
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TM
Curi
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Carpinelli
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AR
D000818:Animals; D002132:Calcium Radioisotopes; D002279:Carcinoma 256, Walker / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D017136:Ion Transport; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D012414:Rubidium Radioisotopes
D002132:Calcium Radioisotopes; D007328:Insulin; D012414:Rubidium Radioisotopes