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Dual role of proapoptotic BAD in insulin secretion and beta cell survival

Genetic evidence of a physiologic role for the proapoptotic family member in glucose-stimulated secretion by beta cells was found by Nika N. Danial and colleagues from the Harvard Medical School's Dana-Farber Cancer Institute (USA).

usually resides in a -containing complex that regulates glucose-driven mitochondrial respiration. The novel function turns out to be specifically dependent upon the phosphorylation of its BH3 sequence, an essential death domain. The scientists analysed the pharmacologic relevance of phosphorylated BH3 with cell-permeable, hydrocarbon-stapled BH3 helices that target , restore glucose-driven mitochondrial respiration and correct the secretory response in -deficient islets. Using this approach they discovered an alternative target and function for the BH3 domain. The phosphorylated BH3 selectively restores beta cell functions and thus bears great therapeutic potential. also regulates the physiologic adaptation of beta cell mass during a high-fat diet.

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