Requirement for translocon-associated protein (TRAP) α in insulin biogenesis
Engineered C. elegans as a model organism for a better understanding of type 2 diabetes in humans.
To better understand the mechanisms of peptide hormones, Xin Li et al. performed a research on translocon associated protein α (TRAPα). They reveal a primordial role of TRAPα in the biosynthesis of insulin. They have used C. elegans as a model organism for mammals to better understand the pathogenesis of type 2 diabetes. The insulin secretion pathway analysis demonstrates the importance of the endoplasmic reticulum translocation machinery in insulin biogenesis. To further extend these findings in rats and humans, they experimented in pancreatic β cells of rats where TRAPα would directly promote preproinsulin translocation, influences proinsulin maturation & insulin secretion. All these advances conduct to suggestions that preproinsulin translocation and proinsulin trafficking could lead to the development of type 2 diabetes.
Abstract: “The mechanistic basis for the biogenesis of peptide hormones and growth factors is poorly understood. Here, we show that the conserved endoplasmic reticulum membrane translocon-associated protein α (TRAPα), also known as signal sequence receptor 1, plays a critical role in the biosynthesis of insulin. Genetic analysis in the nematode Caenorhabditis elegans and biochemical studies in pancreatic β cells reveal that TRAPα deletion impairs preproinsulin translocation while unexpectedly disrupting distal steps in insulin biogenesis including proinsulin processing and secretion. The association of common intronic single-nucleotide variants in the human TRAPα gene with susceptibility to type 2 diabetes and pancreatic β cell dysfunction suggests that impairment of preproinsulin translocation and proinsulin trafficking may contribute to the pathogenesis of type 2 diabetes.”
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