Revisiting an old acquaintance: role for eIF5A in diabetes

Abstract

following combined kidney and nonmyeloablative marrow transplantation: in vivo and in vitro analyses. Am J Transplant. 2006;6(9) Dysfunction of pancreatic islet β cells underlies both type 1 and type 2 diabetes and appears to result in part from the local release of proinflammatory cytokines. An improved understanding of the mechanisms that mediate islet responsiveness to proinflammatory cytokines may therefore expand our knowledge of the role of cytokine signaling in the development of diabetes, providing potential new targets for the development of therapeutics to protect pancreatic islets from inflammation. In this issue of the JCI, Maier and colleagues identify eukaryotic translation initiation factor 5A (eIF5A) as a critical regulator of the inflammatory response in mouse pancreatic islets. I believe these data provide new and important insights into the regulatory pathways that contribute to the development of diabetes and deepen our understanding of the function of the, so far, rather enigmatic cellular protein eIF5A.

A novel mouse model for inhibition of DOHH mediated hypusine modification reveals crucial function for embryonic development, proliferation and oncogenic transformation

“…Interestingly, although both transcripts are targets of eIF5A regulation, they do not encode typical polyproline stretches (three or more consecutive proline residues). It is therefore conceivable that, during evolution, eIF5A gained activities in addition to its primary role in translation elongation, such as the promotion of cytoplasmic accumulation of specific transcripts ( Hauber, 2010 ). It is evident that such an activity would result in indirect effects on translation initiation, particularly in higher multicellular eukaryotes.…”

Repositioning the Old Fungicide Ciclopirox for New Medical Uses

“…Diabetes mellitus, or simply diabetes, is a kind of metabolic disease in which one has abnormally high levels of blood sugar over a prolonged period. Diabetes can be classified into two major types: Type I (insufficient insulin produced in the body), and Type II (insensitivity of cells to insulin) [74]. The hypo-insulin status stems from the malfunction or even loss of islet β cells [74], which are responsible for secreting insulin [75].…”

“…Diabetes can be classified into two major types: Type I (insufficient insulin produced in the body), and Type II (insensitivity of cells to insulin) [74]. The hypo-insulin status stems from the malfunction or even loss of islet β cells [74], which are responsible for secreting insulin [75]. The pro-inflammatory cytokine induces expression of inducible nitric oxide synthase, which, in turn, produces nitric oxide leading to blockage of ATP production, inhibition of insulin secretion, and induction of β cell death [75].…”

Biological Relevance and Therapeutic Potential of the Hypusine Modification System

“…1A). Hypusine is mandatory for eIF-5A activity and function (7,8), and only hypusinated eIF-5A was shown to control translation elongation as well as the nuclear export of spe-cific mRNAs (9,10). Moreover, recent studies linked eIF-5A to the translational control of proteins containing consecutive proline residues (11).…”