zebrafish islet

INTRODUCTION: Congenital hyperinsulinism (HI) is the leading cause of persistent hypoglycemia in infants. Current models to study the most common and severe form of HI resulting from inactivating mutations in the ATP-sensitive potassium channel (KATP ) are limited to primary islets from patients and the Sur1 -/- mouse model. Zebrafish exhibit potential as a novel KATP HI model since they express canonical insulin secretion pathway genes and those with identified causative HI mutations...

Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1...

Type 2 diabetes (T2D) has become a worldwide epidemic, primarily driven by obesity from overnutrition and sedentariness. Recent results reveal there is heterogeneity in both pathology and treatment responses in T2D patients. Therefore, a variety of T2D animal models are necessary to obtain a mechanistic understanding of distinct disease processes. T2D results from insufficient insulin, either due to beta cell loss or inborn deficiency. Although decreases in beta cell mass can occur through loss of identity or cell death, in this review, we will highlight the T2D animal models that display beta cell death, including the Zucker Diabetic Fatty Rat, sand rat, db/db mouse, and a novel diabetic zebrafish model, the Zebrafish Muscle Insulin-Resistant (zMIR) fish...

Alpha lipoic acid (ALA) is a dietary supplement that has been used to treat a wide range of diseases including obesity and diabetes and have lipid-lowering effects, making it a potential candidate for mitigating dyslipidemia resulting from exposures to the per- and polyfluoroalkyl substance (PFAS) family member perfluorooctanesulfonic acid (PFOS). ALA can be considered a non-fluorinated structural analog to PFOS due to their similar 8-carbon chain and amphipathic structure, but, unlike PFOS, is rapidly metabolized...

The study aimed to investigate the antioxidant and antidiabetic activity of Brugmansia arborea L. flower extracts, solvent fractions, and isolated compounds. B. arborea L flowers were extracted with aqueous methanol, and concentrated extract was successively partitioned into EtOAc, n -BuOH, and H2 O fractions. Repeated silica gel and octadecyl silica gel column chromatographies for EtOAc and n -BuOH fractions led to the isolation of a new phenylalkyl glycoside ( 6 ), along with five known ones. Several spectroscopic data led to the structure determination of one new phenylalky glycoside as brugmansioside C (named) ( 6 ) and five known ones as benzyl- O - β -D-glucopyranoside ( 1 ), benzyl- O - β -D-glucosyl-(1→6)- β -D-glucopyranoside ( 2 ), 2-phenylethyl- O - β -D-glucopyranoside ( 3 ), 2-phenylethyl- O - β -D-glucosyl-(1→6)- β -D-glucopyranoside ( 4 ), and 3-phenylpropyl- O - β -D-glucopyranoside ( 5 )...

Chronic inflammation is the underlying cause of many diseases, including type 1 diabetes, obesity, and non-alcoholic fatty liver disease. Macrophages are continuously recruited to tissues during chronic inflammation where they exacerbate or resolve the pro-inflammatory environment. Although leukotriene B4 receptor 2 (BLT2) has been characterized as a low affinity receptor to several key eicosanoids and chemoattractants, its precise roles in the setting of inflammation and macrophage function remain incompletely understood...

AIMS/HYPOTHESIS: Recovering functional beta cell mass is a promising approach for future diabetes therapies. The aim of the present study is to investigate the effects of adjudin, a small molecule identified in a beta cell screen using zebrafish, on pancreatic beta cells and diabetes conditions in mice and human spheroids. METHODS: In zebrafish, insulin expression was examined by bioluminescence and quantitative real-time PCR (qPCR), glucose levels were examined by direct measurements and distribution using a fluorescent glucose analogue, and calcium activity in beta cells was analysed by in vivo live imaging...

Interrupting glucagon signaling decreases gluconeogenesis and the fractional extraction of amino acids by liver from blood resulting in lower glycemia. The resulting hyperaminoacidemia stimulates α cell proliferation and glucagon secretion via a liver-α cell axis. We hypothesized that α cells detect and respond to circulating amino acids levels via a unique amino acid transporter repertoire. We found that Slc7a2ISLC7A2 is the most highly expressed cationic amino acid transporter in α cells with its expression being three-fold greater in α than β cells in both mouse and human...

Butylparaben (BP), a common chemical preservative in cosmetic and pharmaceutical products, has been known to induce oxidative stress and disrupt endocrine function in humans. In contrast, morin, a flavonoid derived from the Moraceae family, exhibits diverse pharmacological properties, including anti-inflammatory and antioxidant. Despite this, the protective role of morin against oxidative stress-induced damage in pancreatic islets remains unclear. Therefore, in this study, we aimed to investigate the potential protective mechanism of morin against oxidative stress-induced damage caused by BP in zebrafish larvae...

Delgadillo-Silva, L. F., Akhtar, M. N., Tasoz, E., Ninov, N. Simultaneous calcium imaging and glucose stimulation in living zebrafish to investigate in vivo beta-cell function. Journal of Visualized Experiments. (175), e62347 (2021). Felix-Martinez, G. J.,Nicolas-Mata, A., Godinez-Fernandez, J. R. Computational reconstruction of pancreatic islets as a tool for structural and functional analysis. Journal of Visualized Experiments. (181), e63352 (2022). Huber, M. K. et al. Observing islet function and islet-immune cell interactions in live pancreatic tissue slices...

Diabetes is a prevalent and debilitating metabolic disorder affecting a large population worldwide. The condition is characterized by insulin resistance and impaired function of pancreatic β-cells, leading to elevated blood glucose levels. In this study, the antidiabetic effects of Erigeron annuus extract (EAE) on zebrafish with damaged pancreatic islets caused by insulin resistance were investigated. The study utilized the zebrafish model to monitor live pancreatic islets. RNA sequencing was also conducted to determine the mechanism by which EAE exerts its antidiabetic effect...

Tert-Butylhydroquinone (tBHQ), a preservative used to prevent oxidative deterioration of oil, fat, and meat products, has been linked to both chemoprotective and adverse effects. This study investigates the impact of dietary tBHQ consumption on survival, growth parameters, organ development, and gene expression in zebrafish (Danio rerio). As tBHQ activates the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2a), a zebrafish line with a mutation in the DNA-binding domain of Nrf2a was used to identify Nrf2a-dependent vs independent effects...

Platycodon grandiflorus (balloon flower), used as a food reserve as well as in traditional herbal medicine, is known for its multiple beneficial effects. In particular, this plant is widely used as a vegetable in Republic of Korea. We examined the ameliorative effects of P. grandiflorus on alloxan-induced pancreatic islet damage in zebrafish. The aerial part treatment led to a significant recovery in pancreatic islet size and glucose uptake. The efficacy of the aerial part was more potent than that of the root...

Pancreatic ɛ-cells producing ghrelin are one type of endocrine cell found in islets, which have been shown to influence other intra-islet cells, especially in regulating the function of β cells. However, the role of such cells during β-cell regeneration is heretofore unknown. Here, using a zebrafish nitroreductase (NTR)-mediated β-cells ablation model, we uncover that ghrelin-positive ɛ-cells in the pancreas act as contributors to neogenic β-cells after extreme β-cell loss...

Here, we provide an optimized protocol to observe the interactions between infiltrating immune cells and islet β cells using live imaging. This protocol is useful for the characterization of cell-cell interactions and for the direct visualization of immune cell migration to the principal pancreatic islet during islet inflammation. We describe the preparation of zebrafish transgenic lines and detail steps for setting up the fish for live confocal imaging. For more details on the use and execution of this protocol, please refer to Yang et al...

Glucagon has emerged as a key regulator of extracellular amino acid (AA) homeostasis. Insufficient glucagon signaling results in hyperaminoacidemia, which drives adaptive proliferation of glucagon-producing α cells. Aside from mammalian target of rapamycin complex 1 (mTORC1), the role of other AA sensors in α cell proliferation has not been described. Here, using both genders of mouse islets and glucagon receptor (gcgr)-deficient zebrafish (Danio rerio), we show α cell proliferation requires activation of the extracellular signal-regulated protein kinase (ERK1/2) by the AA-sensitive calcium sensing receptor (CaSR)...

AIMS/HYPOTHESIS: Genome-wide studies have uncovered multiple independent signals at the RREB1 locus associated with altered type 2 diabetes risk and related glycaemic traits. However, little is known about the function of the zinc finger transcription factor Ras-responsive element binding protein 1 (RREB1) in glucose homeostasis or how changes in its expression and/or function influence diabetes risk. METHODS: A zebrafish model lacking rreb1a and rreb1b was used to study the effect of RREB1 loss in vivo...

Dimethyl fumarate (DMF) is pharmaceutical activator of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates of many cellular antioxidant response pathways, and has been used to treat inflammatory diseases such as multiple sclerosis. However, DMF has been shown to produce adverse effects on offspring in animal studies and as such is not recommended for use during pregnancy. The goal of this work is to better understand how these adverse effects are initiated and the role of DMF-induced Nrf2 activation during three critical windows of development in embryonic zebrafish (Danio rerio): pharyngula, hatching, and protruding-mouth stages...

OBJECTIVES: Tris(4-chlorophenyl) methane (TCPM) and tris(4-chlorophenyl)methanol (TCPMOH) are anthropogenic environmental contaminants believed to be manufacturing byproducts of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) due to environmental co-occurrence. TCPM and TCPMOH are persistent, bioaccumulate in the environment, and are detected in human breast milk and adipose tissues. DDT exposures have been previously shown to disrupt insulin signaling and glucoregulation, increasing risk for diabetes...

ATP-sensitive potassium channel (KATP )gain- (GOF) and loss-of-function (LOF) mutations underlie human neonatal diabetes mellitus (NDM) and hyperinsulinism (HI), respectively. While transgenic mice expressing incomplete KATP LOF do reiterate mild hyperinsulinism, KATP knockout animals do not exhibit persistent hyperinsulinism. We have shown that islet excitability and glucose homeostasis are regulated by identical KATP channels in zebrafish. SUR1 truncation mutation (K499X) was introduced into the abcc8 gene to explore the possibility of using zebrafish for modeling human HI...