Inhibition of glucose‐induced insulin secretion by interleukin‐1β (IL‐1β), or IL‐1β plus tumour necrosis factor‐α (TNF‐α), was less marked when rat islets of Langerhans were cultured for 12 h with these cytokines in L‐arginine‐free medium as opposed to medium containing L‐arginine (1 mM). Inhibition of secretion by IL‐1β was further alleviated when islets were maintained in L‐arginine‐free medium supplemented with N‐ω‐nitro‐L‐arginine methyl ester (NAME), while synergism between IL‐1β plus TNF‐α was completely abolished. Tissue culture medium nitrite levels were raised in islets treated with IL‐1β or TNF‐α (48 h). Cytokine‐stimulated nitrite production was not observed in islets cultured with NAME (1 mM). In conclusion, an L‐arginine‐dependent nitric oxide generating mechanism is involved in the inhibition of insulin secretion by IL‐1β, and accounts for the phenomenon of synergism between IL‐1β and TNF‐α.

Glucose-induced insulin secretion from islets cultured in the presence of interleukin-6 (IL-6) for 12-24 h was inhibited to a similar extent as when islets were treated with interleukin-1 beta (IL-1 beta). However, unlike IL-1 beta, IL-6 did not potentiate insulin secretion during an acute (30 min) exposure of islets to the cytokine, nor did it inhibit DNA synthesis during a 24 h culture period. A 12 h pretreatment of islets with tumour necrosis factor-alpha (TNF-alpha) combined with IL-1 beta potentiated the inhibitory effect of IL-1 beta on secretion, such that 20 mM-glucose-induced insulin secretion was abolished. No synergistic inhibition of secretion was observed with TNF-alpha and IL-6. However, IL-1 beta and IL-6 were found to inhibit insulin secretion in an additive manner. These results suggest that IL-6 inhibits insulin secretion in a manner distinct from that of IL-1 beta, and that IL-6 is unlikely to mediate the inhibitory effects of IL-1 beta or TNF-alpha on rat islets of Langerhans.

The studies describe alterations after hypophysectomy in the proportion of the type-1 and type-2 fibres in rat skeletal muscles, and the effects of replacement treatment with pituitary human (h) GH. Cytochemical analysis of myosin ATPase, succinate dehydrogenase and lactate dehydrogenase activities in sections of rat hind limb muscles were used as markers of fibre type and revealed that hypophysectomy reduced the proportion of type-1 fibres by 50% in soleus and in extensor digitorum longus muscles. This reduction in the proportion of type-1 fibres was accompanied by the appearance of transitional fibres (type 2C/1B). Following seven daily injections of hGH (60 mIU/day) to hypophysectomized rats, the proportion of type-1 fibres in both soleus and in extensor digitorum longus was increased with a concomitant reduction in the number of transitional fibres. After 11 days of treatment, all these transitional fibres had reverted back to type-1 fibres. Only hGH was observed to elicit this effect; injections of other pituitary hormones had no effect on the proportions of these transitional fibres. These alterations in fibre type occurred more rapidly than the changes reported after prolonged electrical stimulation of muscle or following extended exercise. These findings suggest that hypophysectomy and GH injection can result in a rapid alteration in the fibre composition of skeletal muscle, which may have important implications in terms of the resistance to fatigue and speed of contraction of the muscle.

Zona glomerulosa cell suspensions with less than 5 % fasciculata-reticularis cell contamination were prepared by collagenase digestion of normal rat adrenal capsular tissue. The corticosterone and aldosterone content of such cell suspensions under various conditions were measured simultaneously. Increases in steroid production were observed with physiological concentrations of angiotensin 11 (2 \ m=x\10\m=-\11 mol/l), with sigmoid log dose-response curves for both corticosterone and aldosterone production (ED50:4 \m=x\10\m=-\10and 8 \m=x\10\m=-\10mol angiotensin II/l respectively). The response to angiotensin II could be abolished by [Sar1, Ala8]-angiotensin II ; 50 % inhibition was produced by an equimolar concentration of this antagonist. Extracellular potassium ion concentration was shown to affect steroid output dramatically, confirming previous observations and underlining its importance as a physiological regulator of aldosterone secretion. The characteristics of the effect of serotonin, a potent stimulator of steroidogenesis in this system, were also observed. Differences in the maximal responses to angiotensin II and serotonin could not be explained by degradation and probably reflect their different modes of action.Zona fasciculata-reticularis cell suspensions were prepared in a similar fashion from decapsulated adrenal glands, and showed no increase in steroid production with those concentrations of angiotensin II (2 \m=x\10\m=-\11to 2 \m=x\10\m=-\7 mol/l) that stimulated glomerulosa cells. However, angiotensin II amide did increase corticosterone production in isolated fasciculata-reticularis cells at concentrations greater than 2 \m=x\ 10\ m=-\ 5mol / l , as reported by others, whereas angiotensin free acid did not.It is concluded that this sensitive rat glomerulosa cell suspension will be useful for studying the modes of action of angiotensin II and other stimulators of aldosterone biosynthesis.