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Assessing the response of pancreatic islet cells to glucose stimulation is important for understanding β-cell function. Zebrafish are a promising model for studies of metabolism in general, including stimulus-secretion coupling in the pancreas. We used transgenic zebrafish embryos expressing a genetically-encoded Ca sensor in pancreatic β-cells to monitor a key step in glucose induced insulin secretion; the elevations of intracellular [Ca]. In vivo and ex vivo analyses of [Ca] demonstrate that β-cell responsiveness to glucose is well established in late embryogenesis and that embryonic β-cells also respond to free fatty acid and amino acid challenges. In vivo imaging of whole embryos further shows that indirect glucose administration, for example by yolk injection, results in a slow and asynchronous induction of β-cell [Ca] responses, while intravenous glucose injections cause immediate and islet-wide synchronized [Ca] fluctuations. Finally, we demonstrate that embryos with disrupted mutation of the Ca1.2 channel gene cacna1c are hyperglycemic and that this phenotype is associated with glucose-independent [Ca] fluctuation in β-cells. The data reveal a novel central role of cacna1c in β-cell specific stimulus-secretion coupling in zebrafish and demonstrate that the novel approach we propose - to monitor the [Ca] dynamics in embryonic β-cells in vivo - will help to expand the understanding of β-cell physiological functions in healthy and diseased states.
This article was published in the following journal.
Zebrafish embryos are transparent and develop rapidly outside the mother, thus allowing for excellent in vivo imaging of dynamic biological processes in an intact and developing vertebrate. However, t...
Extracellular recordings of neuronal cells are frequently a part of in vitro and in vivo experimental studies as a means of monitoring network-level dynamics. Their connections to intracellular dynami...
Pancreatic β cells produce insulin and play a central role in glucose homeostasis. The regenerative capacity of mammalian β cells is limited, so that loss and dysfunction of β cells causes diabetes...
In this study we combine assays using mouse embryonic stem cells (mESCs) and zebrafish embryos to evaluate the potential developmental toxicity of industrial and pharmaceutical chemicals. A set of ele...
Studies have demonstrated that zebrafish are powerful tools for monitoring environmental toxicity, including radiation hazard. Here we investigated the developmental toxicity of ionizing radiation (IR...
The study consists in a co-clinical trial by using zebrafish embryos. Specifically, an observational prospective clinical trial on patients operated of epato-biliar-pancreatic cancers and ...
This study evaluates the ability to support diagnosis and monitor of the dynamics in ADD/ADHD subjects with an easy to use EEG Device.
New markers of viral activity are now under investigation. Aim of the study is to investigate the efficacy of new antiretroviral drugs by monitoring HIV-DNA dynamics in HIV-positive popula...
This Clinical Study has been designed to assess and compare the impact of in vitro or in vivo culture conditions on the euploidy of sibling blastocysts.
This study will: Evaluate the in vivo effects of treatment with eMatrixCO2 and to determine the dynamics of their development over time following treatment.
Cell surface proteins that bind pancreatic hormones with high affinity and trigger intracellular changes which influence the behavior of cells. These include receptors for glucagon (secreted by alpha cells), insulin (secreted by beta cells), somatostatin (secreted by delta cells), and pancreatic peptide (secreted by PP cells). Some of these hormones and receptors also support neurotransmission.
A 36-amino acid pancreatic hormone that is secreted mainly by endocrine cells found at the periphery of the ISLETS OF LANGERHANS and adjacent to cells containing SOMATOSTATIN and GLUCAGON. Pancreatic polypeptide (PP), when administered peripherally, can suppress gastric secretion, gastric emptying, pancreatic enzyme secretion, and appetite. A lack of pancreatic polypeptide (PP) has been associated with OBESITY in rats and mice.
A primary malignant neoplasm of the pancreatic ISLET CELLS. Usually it involves the non-INSULIN-producing cell types, the PANCREATIC ALPHA CELLS and the pancreatic delta cells (SOMATOSTATIN-SECRETING CELLS) in GLUCAGONOMA and SOMATOSTATINOMA, respectively.
Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).
Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).
Pancreatitis Acute pancreatitis is inflammation of the pancreas caused by the release of activated pancreatic enzymes. Common triggers are biliary tract disease and chronic heavy alcohol intake. Diagnosis is based on clinical presentation...
The pancreas secretes a number of important hormones into the digestive tract and the blood stream. Cancers are most commonly exocrine than endocrine (neuroendocrine) tumors. Functional tumors secrete hormones; Insulinoma, Gastrinoma, Somatostatinoma, VI...