Functional and morphological effects of interleukin-1? on the perfused rat pancreas

Abstract

We recently reported a potentiating effect of recombinant human interleukin-1 beta on glucose-stimulated insulin release from the isolated perfused pancreas. With the aim of determining whether the stimulatory effect of recombinant interleukin-1 beta on the B cell in the intact gland was modulated by varying the concentration, time of exposure to recombinant interleukin-1 beta or B-cell activity, and to elucidate a possible mechanism of action, we measured in the perfused rat pancreas the release of insulin, glucagon and/or prostaglandin E2 according to the following three different protocols: (1) perfusion with 20 ng/ml of recombinant interleukin-1 beta for 92 min at 5 and 20 mmol/l D-glucose (2) perfusion with varying concentrations of recombinant interleukin-1 beta ranging from 0.1 x 10(-3) ng/ml to 100 ng/ml at 5 and 20 mmol/l D-glucose (3) perfusion with 20 ng/ml of recombinant interleukin-1 beta at 5, 11 or 20 mmol/l D-glucose. Furthermore, in a separate set of experiments we examined the influence of the cytokine on the morphology of the endocrine pancreas. Interleukin-1 beta stimulated insulin secretion at 11 and 20 mmol/l D-glucose and potentiated first as well as second phase insulin release in a dose-dependent fashion, with decreasing effect at higher concentrations. Glucagon secretion was also stimulated by recombinant interleukin-1 beta, irrespective of increasing glucose (5, 11, 20 mmol/l) and insulin concentrations. The potentiating effect of recombinant interleukin-1 beta on insulin secretion was evident even after discontinued perfusion with the cytokine, suggesting a priming effect on B-cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

Pancreatic beta‐cell function and interleukin‐1β in plasma during the acute phase response in patients with major burn injuries

“…Since insulin secretion from the isolated pancreas is unaffected by co-perfusion with ET [32] cytokines may act as secondary mediators. In support of this notion is that IL-I fi stimulates insulin secretion from isolated islets [2] and that a bolus injection of IL-I to normal rats mimics the effects of ET on insulin release ex uiuo and in vivo [33,34,35]. However, plasma insulin levels and IL-1p did not correlate in the present study.…”

Cytotoxic action of IL‐1β against pancreatic islets is mediated via nitric oxide formation and is inhibited by NG‐monomethyl‐l‐arginine

“…It is of interest that non-toxic actions of IL-1/~ on beta islet cells, i.e. the modulation of insulin secretion after glucose challenge, also have been reported [7,10]. And it was shown very recently that the 1L-1/~-induced inhibition of insulin secretion is also reversible by adding NMA [14,15].…”

“…IL-I,O alone or in synergy with TNF-ct and IFN-was shown to slowly kill islet cells in isolated islets ur perfused pancreata [8][9][10].…”

Nitric Oxide Is Important for Mouse Beta-Cell Line Killing by Peritoneal Exudate Cells Obtained from Cyclophosphamide Treated Non-Obese Diabetic Mice.

“…But, since macrophages have many functions in immune responses, macrophages are thought to also be final effector cells in pancreatic beta-cell destruction [8,16]. Interleukin 1 and nitric oxide were regarded as important mediators of beta-cell destruction by macrophage [8][9][10][11][12][13][14]. Since these researchers , however, used an effector (cells or cytokine) from non-diabetic subjects, it is uncertain whether nitric oxide plays a role during the progression of diabetes.…”

“…Previously interleukin 1 was regarded as an important mediator of beta-cell destruction of macrophages [5][6][7][8][9][10]. Recently it was clarified that macrophages had an inducible form of nitric oxide synthase and could produce large amounts of nitric oxide [11], which was highly cytotoxic.…”