Summary
To study the functional role of the lysosomes in islet physiology, we have in the present study investigated influences on insulin secretion induced by a primary inhibition of islet lysosomal enzyme activities by the use of the lysosomotropic drug suramin.
First, we demonstrated that the activities of the three lysosomal enzymes, acid amyloglucosidase, acid α-glucosidase, andN-acetyl-β-D-glucosaminidase, were inhibited in mouse islet homogenates upon direct addition of suraminp<0.001). Thereafter, we studied the influences of suramin on islet lysosomal enzyme activities at 24 h after an administration of suramin to mice. We thereby found that the islet lysosomal enzyme activities were not significantly altered compared to controls. However, after incubation of the islets at 3.3 mM glucose, the activities of acid amyloglucosidase and acid α-glucosidase were increasedp<0.05). The activity ofN-acetyl-β-D-glucosaminidase was, however, not affected. Hence, the direct inhibitory action on islet lysosomal enzyme activities by suramin seems to be counteracted in vivo. Concurrently with the increased enzyme activities in incubated islets, glucose-induced insulin secretion was significantly potentiated by suramin pretreatment (p<0.01). In contrast, suramin pretreatment did impair the glucose-induced insulin secretion in vivo (p<0.01).
The direct effects on plasma insulin and glucose levels of acutely administered suramin were also studied. It was found that at a high dose level, suramin slightly reduced the basal plasma insulin levels (p<0.05). Suramin did not, however, affect the glucose-induced increase in plasma insulin levels. Conversely, at a low dose level, suramin potentiated glucose-induced increase in plasma insulin levels (p<0.01). A similar potentiated glucose-induced insulin secretion by suramin was also observed by a direct addition of the drug to islets in vitro.
In conclusion, this study demonstrates that suramin inhibits lysosomal enzyme activities in islet homogenates, increases the activity of acid amylo-glucosidase and acid α-glucosidase in incubated mouse islets after administration of the drug in vivo and potentiates glucose-stimulated insulin secretion from islets in vitro after administration of the drug in vivo. Thus, we suggest first, that in vivo, compensatory mechanisms may counteract the direct inhibitory influence of suramin on islet lysosomal enzyme activities, and second, that in vitro, islet lysosomal acid amyloglucosidase and acid α-glucosidase activities and glucose-induced insulin secretion are regulated in parallel.
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Skoglund, G., Ahrén, B. & Lundquist, I. Insulin secretion and islet lysosomal enzyme activities in the mouse. Int J Pancreatol 4, 29–40 (1989). https://doi.org/10.1007/BF02924145
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DOI: https://doi.org/10.1007/BF02924145