A total of 40 individuals with diabetes (1.8% of early onset sub-group and 0.6% of adult onset sub-group) were carriers of known pathogenic missense variants in the GCK, HNF1A, HNF4A, ABCC8, and INS genes.
One hundred rats were divided into 5 groups: induced DM + RESV administration (DM + RESV; n = 20); induced DM plus placebo solution administration (DM + PLAC; n = 20); induced DM plus insulin therapy (DM + INS; n = 20); induced DM plus administration of RES and INS (DM + RESV + INS; n = 20); and nondiabetic controls (NDM; n = 20).
We identified differentially expressed miRNAs in limbus vs. central cornea in normal and diabetic (DM) corneas including both type 1 (T1DM/IDDM) and type 2 (T2DM/NIDDM) diabetes.
Non-alcoholic fatty liver disease and impaired proinsulin conversion as newly identified predictors of the long-term non-response to a lifestyle intervention for diabetes prevention: results from the TULIP study.
Diabetes develops when the beta cell is stressed because of increased demand for insulin, as observed in individuals with other insulin mutations that affect the processing of proinsulin to insulin or mutations that reduce the affinity for the insulin receptor.
Tolerizing vaccination of NOD mice with a cDNA plasmid expressing full-length proinsulin prevented diabetes, whereas plasmids encoding ZnT8 and DβH did not.
This was associated with diminished glucose-stimulated insulin secretion, increased ROS formation, and accumulation of proinsulin, all characteristics of human diabetes.
We identified one missense mutation (G32S) in the INS gene and two mutations (R131Q and R203S) in the HNF1α gene that could be associated with diabetes.
The mean (SD) insulitis score was significantly reduced (1.156 [0.575] vs 2.156 [0.892] or 3.043 [0.728], P = 0.009 or <0.001), and diabetes was nearly completely prevented (1/13 vs 5/12 or 4/9, P = 0.031 or 0.013) in recipients of transduced HSCs expressing proinsulin II as compared with recipients of nontransduced HSCs or unmanipulated control.
Proinsulin folding within the endoplasmic reticulum (ER) remains incompletely understood, but it is clear that in mutant INS gene-induced diabetes of youth (MIDY), progression of the (three) native disulfide bonds of proinsulin becomes derailed, causing insulin deficiency, β-cell ER stress, and onset of diabetes.
Collectively, the (pre)proinsulin mutants provide insightful molecular models to better understand the pathogenesis of all forms of diabetes in which preproinsulin processing defects, proinsulin misfolding, and ER stress are involved.
Here, we study Type 1 Diabetes Mellitus (T1D), focusing on growth of glutamate, β-alanine, taurine and hypotaurine, and butanoate metabolisms involved in onset of GAD and INS genes in Homo sapiens with comparative analysis in non-obese diabetic Mus musculus, biobreeding Diabetes-prone Rattus norvegicus, Pan troglodytes, Oryctolagus cuniculus, Danio rerio and Drosophila melanogaster respectively.
Given the frequent tendency of heterozygous INS mutations to exhibit dominant negative disease pathogenesis, it is likely that the mutant preproinsulin perturbed the non-mutant counterpart progression and processing within the β-cells, and this resulted to a permanent form of congenital diabetes.