Type 2 diabetes (T2D) is associated with compromised identity of insulin-producing pancreatic islet β cells, characterized by inappropriate production of other islet cell-enriched hormones. Here, we examined how hormone misexpression was influenced by the MAFA and MAFB transcription factors, closely related proteins that maintain islet cell function. Mice specifically lacking MafA in β cells demonstrated broad, population-wide changes in hormone gene expression with an overall gene signature closely resembling islet gastrin+ (Gast+) cells generated under conditions of chronic hyperglycemia and obesity.
View Article and Find Full Text PDFThe adipocyte-derived hormone leptin increases trafficking of K and Kv2.1 channels to the pancreatic β-cell surface, resulting in membrane hyperpolarization and suppression of insulin secretion. We have previously shown that this effect of leptin is mediated by the NMDA subtype of glutamate receptors (NMDARs).
View Article and Find Full Text PDFThe adipocyte hormone leptin was first recognized for its actions in the central nervous system to regulate energy homeostasis but has since been shown to have direct actions on peripheral tissues. In pancreatic β-cells leptin suppresses insulin secretion by increasing K channel conductance, which causes membrane hyperpolarization and renders β-cells electrically silent. However, the mechanism by which leptin increases K channel conductance had remained unresolved for many years following the initial observation.
View Article and Find Full Text PDFNMDA receptors (NMDARs) are Ca-permeant, ligand-gated ion channels activated by the excitatory neurotransmitter glutamate and have well-characterized roles in the nervous system. The expression and function of NMDARs in pancreatic β-cells, by contrast, are poorly understood. Here, we report a novel function of NMDARs in β-cells.
View Article and Find Full Text PDFMany animal species communicate using chemical signals. In Drosophila, cuticular hydrocarbons (CHCs) are involved in species and sexual identification, and have long been thought to act as stimulatory pheromones as well. However, a previous study reported that D.
View Article and Find Full Text PDFLittle is currently known about the genetic complexity of quantitative behavioral variation, the types of genes involved, or their effects on intermediate phenotypes. Here, we conduct a genome-wide association study of Drosophila melanogaster courtship song variation using 168 sequenced inbred lines, and fail to find highly significant associations. However, by combining these data with results from a well-powered Evolve and Resequence (E&R) study on the same trait, we provide statistical evidence that some power to associate genotype and phenotype is available.
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