A5025694971- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diabetes Management and Research
- Aquaculture disease management and microbiota
- Metabolism, Diabetes, and Cancer
- Stress Responses and Cortisol
- Adipose Tissue and Metabolism
- Regulation of Appetite and Obesity
- Diabetes Treatment and Management
- Diet, Metabolism, and Disease
- Aquaculture Nutrition and Growth
- Genomics and Chromatin Dynamics
- interferon and immune responses
- Hormonal Regulation and Hypertension
- Epigenetics and DNA Methylation
- Invertebrate Immune Response Mechanisms
- Physiological and biochemical adaptations
- Receptor Mechanisms and Signaling
- Endoplasmic Reticulum Stress and Disease
- Chemokine receptors and signaling
- Adipokines, Inflammation, and Metabolic Diseases
- Biochemical Analysis and Sensing Techniques
- Genetics and Neurodevelopmental Disorders
- Estrogen and related hormone effects
- Birth, Development, and Health
University of California, Davis
2015-2024
University of California, Los Angeles
2020
Cleveland Clinic
2016
Salk Institute for Biological Studies
2008-2015
University of Copenhagen
2014
Clayton Foundation
2013
Radboud University Nijmegen
2002-2011
Wageningen University & Research
2002-2007
Netherlands Institute for Neuroscience
2006
Complex local crosstalk amongst endocrine cells within the islet ensures tight coordination of their output. This is illustrated by recent demonstration that negative feedback control delta pancreatic islets determines homeostatic set-point for plasma glucose during mouse postnatal development. However, close association facilitates paracrine also complicates distinction between effects mediated directly on beta from indirect via intermediates, such as somatostatin cells.To resolve this...
Insulin producing beta cell and glucagon alpha cells are colocalized in pancreatic islets an arrangement that facilitates the coordinated release of two principal hormones regulate glucose homeostasis prevent both hypoglycemia diabetes. However, this intricate organization has also complicated determination cellular source(s) expression genes detected islet. This reflects a significant gap our understanding mouse islet physiology, which reduces effectiveness by mice model human disease.To...
Leptin is a key factor in the regulation of food intake and an important pathophysiology obesity. However, more than decade after discovery leptin mouse, information regarding any nonmammalian species still scant. We report identification duplicate genes common carp (Cyprinus carpio). The unique gene structure, conservation both cysteines that form leptin's single disulfide bridge, stable clustering phylogenetic analyses substantiate unambiguous orthology mammalian leptins, despite low amino...
We describe duplicate leptin genes in zebrafish (Danio rerio) that share merely 24% amino acid identity with each other and only 18% human leptin. were also able to retrieve a second gene medaka (Oryzias latipes). The presence of these two distantly related teleosts suggests are common feature teleostean fishes. Despite low primary sequence conservation, we confident assigning orthology between mammalian leptins for several reasons. First, both their characteristic structure display key...
We elucidated the structure of principle factors regulating initiation acute stress response in common carp: corticotrophin-releasing hormone (CRH), CRH-receptor 1 (CRH-R1) and CRH-binding protein (CRH-BP). Phylogenetic analyses reveal that these proteins are evolutionarily well conserved vertebrates. CRH CRH-BP expression not co-localised same hypothalamic perikarya. On contrary, is limited to perimeter nucleus preopticus (NPO), but abundant other regions, including an area directly rostral...
Islet gene expression has been widely studied to better understand the transcriptional features that define a healthy β-cell. Transcriptomes of FACS-purified α-, β-, and δ-cells using bulk RNA-sequencing have facilitated our understanding complex network cross talk between islet cells its effects on β-cell function. However, these approaches were by design not intended resolve heterogeneity individual cells. Several recent studies used single-cell RNA sequencing (scRNA-Seq) report...
The peptide hormone Urocortin 3 (Ucn 3) is abundantly and exclusively expressed in mouse pancreatic beta cells where it regulates insulin secretion. Here we demonstrate that Ucn first appears at embryonic day (E) 17.5 and, from approximately postnatal (p) 7 onwards throughout adult life, becomes a unifying exclusive feature of cells. These observations identify as potential cell maturation marker. To determine whether similarly restricted to humans, conducted comprehensive...
Abstract One of the ultimate goals regenerative medicine is generation patient-specific organs from pluripotent stem cells (PSCs). Sheep are potential hosts for growing human through technique blastocyst complementation. We report here creation pancreatogenesis-disabled sheep by oocyte microinjection CRISPR/Cas9 targeting PDX1 , a critical gene pancreas development. compared efficiency target mutations after microinjecting system in metaphase II (MII) oocytes and zygote stage embryos. MII...
We and others have previously identified a group of genes, dubbed "disallowed", whose expression is markedly lower in pancreatic islets than other mammalian cell types. Forced mis-expression several members this family leads to defective insulin secretion, demonstrating the likely importance disallowance for normal beta function. Up now, transcriptomic comparisons been based solely on data from whole islets. This raises possibilities that (a) there may be important differences degree between...
Adaptation of the islet β cell insulin-secretory response to changing insulin demand is critical for blood glucose homeostasis, yet mechanisms underlying this adaptation are unknown. Here, we have shown that nutrient-stimulated histone acetylation plays a key role in adapting secretion through regulation genes involved nutrient sensing and metabolism. Nutrient epigenome occurred at sites occupied by chromatin-modifying enzyme lysine-specific demethylase 1 (Lsd1) islets. Cell-specific...