Leptin inhibits insulin secretion and preproinsulin gene expression in pancreatic beta-cells, but signal transduction pathways and molecular mechanisms underlying this effect are poorly characterized. In this study, we analyzed leptin-mediated signal transduction and preproinsulin gene regulation at the molecular level in pancreatic beta-cells. Leptin stimulation led to janus kinase (JAK)2-depe...

The insulinotrophic effects of glucagon-like peptide 1 (GLP-1) are mediated by its seven-transmembrane receptor (GLP-1R) in pancreatic beta-cells. We have transiently transfected the GLP-1R and a proopiomelanocortin (POMC) promoter-driven human preproinsulin gene vector (pIRES) into the AtT-20 pituitary corticotrophic cell line, to investigate the possibility of creating a regulated, insulin-ex...

Nascent preproinsulin interacts with endoplasmic reticulum membranes after approximately 70-80 residues of the 116-amino acid precursor are polymerized (Eskridge, E. M., and Shields, D. (1983) J. Biol. Chem. 258, 11487-11491). To understand the relationship between the size of a nascent presecretory polypeptide and the efficiency of its translocation across the endoplasmic reticulum membrane, r...

results this study shows the prepared gene construct is inducible by glucose. gene expression of preproinsulin was observed in muscle tissue of rabbits. conclusions these finding indicated that research in diabetes mellitus gene therapy could be performed on larger animals. objectives the purpose of this study was to construct glucose inducible insulin gene plasmid and use it in the muscle tiss...

Recently, missense mutations upstream of preproinsulin's signal peptide (SP) cleavage site were reported to cause mutant INS gene-induced diabetes of youth (MIDY). Our objective was to understand the molecular pathogenesis using metabolic labeling and assays of proinsulin export and insulin and C-peptide production to examine the earliest events of insulin biosynthesis, highlighting molecular m...

Immunization against insulin, insulin B chain, or B chain peptide B(9-23) (preproinsulin peptide II(33-47)) prevents diabetes in the nonobese diabetic (NOD) mouse. Whether or not peptide II(33-47) is the only proinsulin determinant recognized by CD4 T cells remains unclear. Using two peptide libraries spanning the entire sequence of preproinsulin I and preproinsulin II, respectively, we identif...

Fetal bovine pancreatic poly(A)-containing RNA directs the synthesis of an insulin immunoreactive polypeptide that is larger than proinsulin, preproinsulin, in the wheat germ cell-free translation system. We have characterized this peptide in detail both immunologically and chemically and have shown that it is 2500 daltons larger than bovine proinsulin (8700 daltons), possesses both insulin and...

Brief Summary: This in vitro study explored the reactivity to preproinsulin of CD8 T cells obtained from pancreatic islets individuals with and without type 1 diabetes (T1D). The main finding was that T1D donors were highly reactive peptides throughout entire protein.

Leptin controls feeding behavior and insulin secretion from pancreatic beta-cells. Insulin stimulates the production of leptin, thereby establishing an adipoinsular axis. Earlier we identified leptin receptors on pancreatic beta-cells and showed leptin-mediated inhibition of insulin secretion by activation of ATP-sensitive potassium channels. Here we examine transcriptional effects of leptin on...