ISSN:
1432-0428
Schlagwort(e):
Interleukin-1
;
perfused rat pancreas
;
insulin
;
glucagon
;
Type 1 (insulin-dependent) diabetes mellitus
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary We recently reported a potentiating effect of recombinant human interleukin-1β on glucose-stimulated insulin release from the isolated perfused pancreas. With the aim of determining whether the stimulatory effect of recombinant interleukin-1β on the B cell in the intact gland was modulated by varying the concentration, time of exposure to recombinant interleukin-1β 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-1β for 92 min at 5 and 20 mmol/1 D-glucose (2) perfusion with varying concentrations of recombinant interleukin-1β ranging from 0.1×10−3 ng/ml to 100 ng/ml at 5 and 20 mmol/l D-glucose (3) perfusion with 20 ng/ml of recombinant interleukin-1β 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-1β 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-1β, irrespective of increasing glucose (5, 11, 20 mmol/l) and insulin concentrations. The potentiating effect of recombinant interleukin-1β on insulin secretion was evident even after discontinued perfusion with the cytokine, suggesting a priming effect on B-cell function. Furthermore, we did not observe any relation between the recombinant interleukin-1β mediated insulin and glucagon release and prostaglandin E2. Electron microscopy of the pancreata perfused with recombinant interleukin-1β revealed significant B cell and to a lesser extent A-cell lysis as well as induction of cell protrusions (“blebs”) in B cells only, accompanied by peripheral degranulation and rearrangement of rough endoplasmatic reticulum. We suggest that in addition to a paracrine effect of locally produced interleukin-1β systemic interleukin-1β may have an endocrine effect on A- and B-cell function and viability. Interleukin-1β should be considered to be a physiological modulator of insulin and glucagon secretion e.g. during the acute phase response, but also as a pathogenetic factor in Type 1 (insulin-dependent) diabetes mellitus.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00586456
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