Embryonic exposure to Mono(2-ethylhexyl) phthalate (MEHP) disrupts pancreatic organogenesis in zebrafish (Danio rerio).

Mono(2-ethylhexyl) phthalate (MEHP) is the bioactive metabolite of di(2-ethylhexyl) phthalate, a plasticizing agent and persistent environmental contaminant associated with obesity, developmental abnormalities, and oxidative stress. Nrf2 (Nfe2l2) is a transcription factor that regulates cytoprotective genes as part of the adaptive antioxidant response. We previously identified the pancreas as a sensitive target of oxidative stress during embryonic development.

Assessment of Toxicological Perturbations and Variants of Pancreatic Islet Development in the Zebrafish Model.

The pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue of chemical exposures. However, this endpoint, as well as the integrity of the surrounding exocrine pancreas, is often overlooked in studies of developmental toxicology.

Expression and function of ATP-dependent potassium channels in zebrafish islet β-cells.

ATP-sensitive potassium channels (K channels) are critical nutrient sensors in many mammalian tissues. In the pancreas, K channels are essential for coupling glucose metabolism to insulin secretion. While orthologous genes for many components of metabolism-secretion coupling in mammals are present in lower vertebrates, their expression, functionality and ultimate impact on body glucose homeostasis are unclear.

Embryonic exposures to perfluorooctanesulfonic acid (PFOS) disrupt pancreatic organogenesis in the zebrafish, Danio rerio.

Perfluorooctanesulfonic acid (PFOS) is a ubiquitous environmental contaminant, previously utilized as a non-stick application for consumer products and firefighting foam. It can cross the placenta, and has been repeatedly associated with increased risk for diabetes in epidemiological studies. Here, we sought to establish the hazard posed by embryonic PFOS exposures on the developing pancreas in a model vertebrate embryo, and develop criteria for an adverse outcome pathway (AOP) framework to study the developmental origins of metabolic dysfunction.

Detection of autofluorescent Mycobacterium chelonae in living zebrafish.

Mycobacterium chelonae is widespread in aquatic environments and can cause mycobacteriosis with low virulence in zebrafish. The risk of infection in zebrafish is exacerbated in closed-recirculating aquatic systems where rapidly growing mycobacteria can live on biofilms, as well as in zebrafish tissues. We have discovered a method of identifying and visualizing M.

Imaging beta cell regeneration and interactions with islet vasculature in transparent adult zebrafish.

Blood vessel networks provide nutrients and gaseous exchange that are essential for functions. Pancreatic islet capillaries deliver oxygen to endocrine cells while transporting hormones to organs and peripheral locations throughout the body. We have developed a zebrafish diabetes model in which adult islets can be followed in vivo during beta cell regeneration while calibrating changes in beta cell mass and fasting blood glucose levels.

Deletion of GαZ protein protects against diet-induced glucose intolerance via expansion of β-cell mass.

Insufficient plasma insulin levels caused by deficits in both pancreatic β-cell function and mass contribute to the pathogenesis of type 2 diabetes. This loss of insulin-producing capacity is termed β-cell decompensation. Our work is focused on defining the role(s) of guanine nucleotide-binding protein (G protein) signaling pathways in regulating β-cell decompensation.

Regeneration of the pancreas in adult zebrafish.

Objective: Regenerating organs in diverse biological systems have provided clues to processes that can be harnessed to repair damaged tissue. Adult mammalian beta-cells have a limited capacity to regenerate, resulting in diabetes and lifelong reliance on insulin. Zebrafish have been used as a model for the regeneration of many organs.

Sonic hedgehog is required early in pancreatic islet development.

Pancreatic organogenesis relies on a complex interplay of cell-autonomous and extracellular signals. We demonstrate that the morphogen sonic hedgehog (Shh) is required for pancreatic development in zebrafish. Genetic mutants of Shh and its signaling pathway establish this dependence as specific to endocrine, but not exocrine, pancreas.