Effects of Cytokines on 3-Cell Function

Initial Demonstration of the Effects Interleukin 1 on Islet Function 

In 1985 Nerup and co-workers demonstrated that treatment of isolated rat and human islets with conditioned media derived from activated mononuclear cells resulted in the inhibition of glucose-stimulated insulin secretion (Mandrup-Poulsen et cd., 1985). The cytokine IL-1/3 was found to be the active component of the conditioned media (Bendtzen etal., 1986). Mandrup-Poulsen et al. (1986) further showed that continuous exposure of islets to IL-1 is toxic. 

The pioneering work of Nerup and co-workers provided the initial evidence suggesting that local fluctuations of cytokine concentrations may influence insulin secretion by islets. The effects of IL-1)8 on insulin secretion have been confirmed and extended to show that lL-l/3-induced inhibition of glucose stimulated insulin secretion by isolated islets is both time- and concentration-depen-dent as shown in Fig. 1 (Spinas et al., 1986 Comens et al., 1987 McDaniel et al., 1988a Palmer etal., 1989). Treatment of islets for short periods of time with high concentrations of IL-lj8 (1-10 U/ml) or for longer periods of time with 

Effects of IL-1 on glucose-stimulated insulin secretion Concentration and time dependence. The ability of IL-1 to modulate insulin secretion by isolated rat islets is illustrated. Short exposures of islets to high concentrations of lL-1 [2 nM as shown here, or 5 U/ml (5 pM) as used in other studies], or prolonged exposure to low concentrations of lL-1 (0.5 pM or 0.5 U/ml) result in a stimulation of glucose-induced insulin secretion. Incubation of islets for 18 hr with 2 nM (or 5 U/ml) IL-1 results in a potent and reversible inhibition of glucose stimulated insulin secretion. Islet destruction is observed when islets are treated for 4 to 6 days with 2 nM (or 5 U/ml) lL-1. Reproduced with permission from Diabetes (McDaniel et al, 1988), by the American Diabetes Association, Inc. 

Effects of Interleukin I on mRNA Transcription and Protein Translation 

---