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Human Islet Amyloid Polypeptide or amylin is a neuroendocrine peptide with important endocrine and paracrine functions. Excessive production and accumulation of human amylin in the pancreas can lead to its aggregation and apoptosis of islet β-cells. Amylin has been shown to function within the central nervous system to decrease food intake, and more recently, it has been revealed that amylin is directly transcribed from neurons of the central nervous system, including the hypothalamus, arcuate nucleus, medial preoptic area, and nucleus accumbens. These findings alter the current model of how amylin targets the nervous system, and as a result may lead to obesity and type II diabetes mellitus. Here we set out to use Caenorhabditis elegans as an inducible in vivo model system to study the effects of amylin overexpression in tissues that include the nervous system. We profiled the transcriptional changes in transgenic animals expressing human amylin through RNA-seq. Using this genome-wide approach our results revealed for the first time that expression of human amylin in tissues including the nervous system induce diverse physiological responses in various signaling pathways. From our characterization of transgenic C. elegans animals expressing human amylin, we also observed specific defects in neural developmental programs as well as sensory behavior. Taken together, our data demonstrate the utility of using C. elegans as a valuable in vivo model to study human amylin toxicity.
This article was published in the following journal.
Name: Neuroscience letters
Islet Amyloid Polypeptide (IAPP), also known as amylin, is a 37-amino-acid peptide hormone that is secreted by pancreatic islet β-cells. Amylin is complementary to insulin in regulating and maintaini...
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Amylin acts in the area postrema (AP) and arcuate nucleus (ARC) to control food intake. Amylin also increases axonal fiber outgrowth from the AP→nucleus tractus solitarius (NTS) and from ARC→hypot...
Deposition of islet amyloid consisting of amylin constitutes one of pathological hallmarks of type 2 diabetes mellitus (T2DM), and it may be involved in the development and progression of T2DM. Howeve...
Three pieces of information lead to the basis for this study: 1. Individuals with Type-2 diabetes commonly develop peripheral neuropathy. 2. Increased production of the hormone amyli...
Preptin and amylin are pancreatic hormones which participate in glucose homeostasis. This study aims to evaluate how serum preptin and amylin levels are altered in polycystic ovary syndrom...
Amylin and calcitonin gene related peptide (CGRP) are related to the same peptide family. Both share 16 out of 37 amino acids and can activate each others receptor. CGRP is implicated in m...
The purpose of this study is to identify how certain parts of the brain that help control body weight respond to an infusion of hormones called leptin and amylin.
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A costimulatory receptor that is specific for INDUCIBLE T-CELL CO-STIMULATOR LIGAND. The receptor is associated with a diverse array of immunologically-related effects including the increased synthesis of INTERLEUKIN 10 in REGULATORY T-LYMPHOCYTES and the induction of PERIPHERAL TOLERANCE.
Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc.
Heat and cold stress-inducible, transcription factors that bind to inverted 5'-NGAAN-3' pentamer DNA sequences and are regulated by poly(ADP) ribosylation. They play essential roles as transcriptional activators of the HEAT-SHOCK RESPONSE by inducing expression of large classes of MOLECULAR CHAPERONES and heat-shock proteins. They also function in DNA REPAIR; transcriptional reactivation of latent HIV-1; and pre-mRNA processing and nuclear export of HSP70 HEAT-SHOCK PROTEINS during heat stress.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A B7 antigen that binds specifically to INDUCIBLE T-CELL CO-STIMULATOR PROTEIN on T-CELLS. It provides a costimulatory signal for T-cell proliferation and cytokine secretion.
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Diabetes Diabetes Endocrine Disorders Obesity Oxycontin Renal Disease Thyroid Disorders Endocrinology is the study of the endocrine glands and the hormones that they secrete (Oxford Medical Dictionary). There are several g...