Normal glucose homeostasis depends on the coordinated regulation of insulin production and secretion. Insulin is stored in the pancreatic β-cell until an appropriate stimulus triggers its release. Consequently, a parallel stimulation of proinsulin biosynthesis is necessary to replenish the intracellular insulin stores. Among the diverse insulin secretagogues, glucose is the most physiologically...

Due to their high glucose permeability, insulin-secreting pancreatic beta-cells likely undergo strong intracellular protein glycation at high glucose concentrations. They may, however, be partly protected from the glucotoxic alterations of their survival and function by fructosamine-3-kinase (FN3K), a ubiquitous enzyme that initiates deglycation of intracellular proteins. To test that hypothesi...

Patients with type 1 diabetes (T1D) suffer from beta-cell destruction by CD8+ T-cells that have preproinsulin as an important target autoantigen. It is of great importance to understand the molecular mechanism underlying the processing of preproinsulin into these CD8+ T-cell epitopes. We therefore studied a pathway that may contribute to the production of these antigenic peptides: degradation o...

4 0 The identification and validation of gene-gene interactions is a major challenge in 4 1 human studies. Here, we explore an approach for studying epistasis in humans using a 4 2 Drosophila melanogaster model of neonatal diabetes mellitus. Expression of the mutant 4 3 preproinsulin (hINS C96Y) in the eye imaginal disc mimics the human disease: it activates 4 4 conserved stress response pathwa...

In a variety of mammalian species, small islets secrete more insulin per volume than large islets. This difference may be due to diffusional limitations of large islets, or inherent differences in the insulin production pathways. The purpose of this study was to identify possible differences in the early phase of glucose-stimulated insulin biosynthesis between large and small islets. Isolated s...

Type 2 diabetes mellitus is characterized by insulin resistance. However, the complete molecular mechanism remains unclear. In this study, zebrafish were fed a long-term high-fat diet to induce type 2 diabetes, which resulted in a higher body weight, body mass index, more lipid vacuoles in liver, increased insulin transcription level in liver, brain and muscle, and high fasting blood glucose in...