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<\/p>\nThis project aims to understand how disruptions in the\u00a0redox state contribute to the dysfunction of islet cells and the development of metabolic disorders such as type 2 diabetes. While much is known about beta-cell dysfunction in diabetes, the roles of other endocrine cells in the development of metabolic diseases remain poorly understood. We focus on the role of the\u00a0redox state in intercellular communication in pancreatic islets. These are mainly composed of three types of endocrine cells: alpha (glucagon production), beta (insulin production), and delta (somatostatin production).<\/p>\n
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Abbreviations used:<\/u> IR – insulin receptor, GCGR – glucagon receptor, GLP1R – glucagon-like peptide 1 receptor, SSTR – somatostatin receptor (isoforms 2,3,5), GABA? R – GABA type A receptor (inhibitory neurotransmitter), 5-HT1F R – Serotonin receptor type 1F, CRHR – Corticotropin-releasing hormone receptor, mAChR – Muscarinic acetylcholine receptor, CX36 – Connexin 36, RRP – Ready releasable pool.<\/p>\n
Proper communication within the islet (paracrine and autocrine) and with peripheral tissues (incretins from the digestive system, nervous system, immune system, etc.) is essential for maintaining appropriate blood glucose regulation. Alpha, beta, and delta cells communicate with each other using their own hormones and other signaling substances (see figure) by acting through specific receptors on the surface of target cells. The most attention is directed to the majority population of beta cells. This is further subdivided into other subpopulations, e.g. ‘pacemaker-like Hubb’ cells generating an action potential wave that triggers a synchronous discharge from surrounding cells via gap junctions (CX36).<\/p>\n
Insulin secretion from beta cells is stimulated by increased glucose metabolism, leading to changes in the redox environment and reversible modifications of sensitive proteins (oxidation, acetylation, phosphorylation) (Holendova et al, 2024). Specifically, we are studying a major source of reactive oxygen species (ROS) in beta cells, the enzyme NADPH oxidase 4 (NOX4), which has been described as a key signal amplifier in glucose-stimulated insulin release (Plecita-Hlavata et al, 2020). An imbalance in the redox environment is associated with impaired beta cell function. Deletion of Nox4<\/em> in beta-specific Nox4<\/em>-\/-<\/sup> mutant mice leads to a pro-reduction phenotype. These mice exhibit impaired biphasic insulin secretion and peripheral insulin resistance. Conversely, increased NOX4 activity and a pro-oxidant beta cell environment due to metabolic stress leads to increased systemic inflammation, e.g. on a high-fat diet (Holendova et al, 2024). It is not yet clear how other endocrine cells play a role in the development of health complications. Their involvement in adulthood is particularly important in the development of type 2 diabetes, where various compensatory mechanisms occur that have not yet been fully described.<\/p>\n References:<\/p>\n Holendov\u00e1 B, \u0160alovsk\u00e1 B, Ben\u00e1kov\u00e1 \u0160, Plecit\u00e1-Hlavat\u00e1 L. Beyond glucose: The crucial role of redox signaling in \u03b2-cell metabolic adaptation. Metabolism 2024;161:156027.<\/p>\n Lydie Plecit\u00e1-Hlavat\u00e1,\u00a0Martin Jab\u016frek,\u00a0Blanka Holendov\u00e1,\u00a0Jan Tauber,\u00a0Vojt\u011bch Pavluch,\u00a0Zuzana Berkov\u00e1,\u00a0Monika Cahov\u00e1,\u00a0Katrin Schr\u00f6der,\u00a0Ralf P. Brandes,\u00a0Detlef Siemen,\u00a0Petr Je\u017eek; Glucose-Stimulated Insulin Secretion Fundamentally Requires H2<\/sub>O2<\/sub>\u00a0Signaling by NADPH Oxidase 4.\u00a0Diabetes<\/em>\u00a01 July 2020; 69 (7): 1341\u20131354.\u00a0https:\/\/doi.org\/10.2337\/db19-1130<\/a><\/p>\n Holendov\u00e1 B, Ben\u00e1kov\u00e1 \u0160, K\u0159ivonoskov\u00e1 M, Pavluch V, Tauber J, Gabrielov\u00e1 E, Je\u017eek P, Plecit\u00e1-Hlavat\u00e1 L. NADPH oxidase 4 in mouse \u03b2 cells participates in inflammation on chronic nutrient overload. Obesity (Silver Spring) 2024;32:339-351.<\/p>\n","protected":false},"excerpt":{"rendered":" This project aims to understand how disruptions in the\u00a0redox state contribute to the dysfunction of islet cells and the development of metabolic disorders such as type 2 diabetes. While much is known about beta-cell dysfunction in diabetes, the roles of other endocrine cells in the development of metabolic diseases remain poorly understood. We focus on […]<\/p>\n","protected":false},"author":5,"template":"","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"oddeleni":[186],"poskytovatel":[],"stav-projektu":[209],"class_list":["post-32537","vyzkumny-projekt","type-vyzkumny-projekt","status-publish","hentry","oddeleni-pancreatic-islet-research","stav-projektu-current-projects"],"acf":[],"_links":{"self":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/vyzkumny-projekt\/32537","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/vyzkumny-projekt"}],"about":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/types\/vyzkumny-projekt"}],"author":[{"embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/users\/5"}],"version-history":[{"count":0,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/vyzkumny-projekt\/32537\/revisions"}],"wp:attachment":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/media?parent=32537"}],"wp:term":[{"taxonomy":"oddeleni","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/oddeleni?post=32537"},{"taxonomy":"poskytovatel","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/poskytovatel?post=32537"},{"taxonomy":"stav-projektu","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/stav-projektu?post=32537"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}