Role of polyamines in the regulation of proliferation and hormone production by insulin-secreting cells

Abstract

This paper focuses on the mechanisms regulating proliferation and insulin production by normal and tumoral pancreatic beta-cells. In particular, the evidence for involvement of polyamines is reviewed. Pancreatic islet cells contain high levels of polyamines, and based on findings obtained using enzyme-directed inhibitors, it appears that putrescine and spermidine are necessary for proinsulin biosynthesis, whereas spermine may exert a stimulatory or permissive role in RNA transcription-stabilization and long-term insulin release. Islet polyamine content is not altered by short-term secretory stimulation, nor is the acute secretory response impeded by polyamine synthesis inhibitors, making it unlikely that these amines play any major role in short-term insulin release. Various mitogens increase islet polyamine contents and DNA synthesis, but increases in cytosolic polyamines do not seem to mediate their mitogenicity. Nuclear polyamine content is not altered by the inhibitors, suggesting that maintenance of polyamines within this organelle may be sufficient to sustain elevated DNA synthesis. In tumoral RINm5F cells, polyamine depletion results in decreased proliferation and increased cellular content of insulin and insulin secretory granules without affecting insulin mRNA levels or translation. Moreover, polyamine-depleted RINm5F cells display improved substrate metabolism and sensitivity of the stimulus-secretion coupling. Possible levels of polyamine interaction with Ca2+ metabolism are discussed.