Tumor necrosis factor activity of pancreatic islets.
Leeper-Woodford, Sandra K., and Brian W. Tobin.
Departments of Physiology and Biochemistry, Mercer University
School of Medicine, Macon, Georgia, 31207
APStracts 4:0101E, 1997.
Tumor necrosis factor (TNF) is involved in the pathogenesis of acute
sepsis-induced organ injury and has been implicated as a mediator of
metabolic alterations observed during sepsis. Pancreatic islet cell
function may be significantly compromised during sepsis or
endotoxemia and sepsis also increases plasma levels of epinephrine, a
modifier of islet insulin secretion. We proposed that islets exposed
to bacterial lipopolysaccharide (LPS) produce TNF and that
epinephrine attenuates islet secretory activity. We monitored the
effects of LPS and epinephrine on TNF and insulin activity of
isolated Wistar-Furth rat islets (pancreas digested with collagenase,
islets isolated using Ficoll gradients; n=4 islet populations, each
with 632+11 islets/2.5ml culture medium. Islets were incubated
(37_0_, 5 %C02) 3 days, LPS (Escherichia coli, 1 _[mu]_g/ml) and
epinephrine (14_[mu]_g/ml) were added to the islets and incubations
continued for 1-4 h. Glucose (Beckman glucose analyzer), insulin
(Radioimmunoassay), and TNF (L929 cytotoxicity assay) were measured
in the islet medium samples at 1-4 h time points. In the conditioned
medium, glucose decreased (p<0.05), insulin increased (p<0.05)
and e_xposure to LPS did not alter these levels (p=n.s.), but_ did
increase TNF activity by 400% (p<0.05)_. _Epinephrine reduced
insulin by 38-43% (p<0.05)_ and TNF by 20-25% (p<0.05)_, but had
no effect on glucose levels (p=n.s.). _We conclude that insulin is
secreted from isolated islets and that exposure to LPS acutely
increases islet-derived TNF activity, while epinephrine modifies TNF
and insulin secretion of rat pancreatic islets._
Received 13 February 1997; accepted in final form 23 April 1997.
APS Manuscript Number E71-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 13 May 1997