Publication Date:
2019
Description:
〈p〉Deoxyhypusine synthase (DHPS) uses the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly defined mechanisms. Because germline deletion of 〈i〉Dhps〈/i〉 is embryonically lethal, its role in normal postnatal cellular function in vivo remains unknown. We generated a mouse model that enabled the inducible, postnatal deletion of 〈i〉Dhps〈/i〉 specifically in postnatal islet β cells, which function to maintain glucose homeostasis. Removal of 〈i〉Dhps〈/i〉 did not have an effect under normal physiologic conditions. However, upon development of insulin resistance, which induces β cell proliferation, 〈i〉Dhps〈/i〉 deletion caused alterations in proteins required for mRNA translation and protein secretion, reduced production of the cell cycle molecule cyclin D2, impaired β cell proliferation, and induced overt diabetes. We found that hypusine biosynthesis was downstream of protein kinase C- and was required for c-Myc–induced proliferation. Our studies reveal a requirement for DHPS in β cells to link polyamines to mRNA translation to effect facultative cellular proliferation and glucose homeostasis.〈/p〉
Print ISSN:
1945-0877
Electronic ISSN:
1937-9145
Topics:
Biology
,
Medicine
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