Involvement of dying beta cell originated messenger molecules in differentiation of pancreatic mesenchymal stem cells under glucotoxic and glucolipotoxic conditions

Abstract

Beta cell mass regulation represents a critical issue for understanding and treatment of diabetes. The most important process in the development of diabetes is beta cell death, generally induced by glucotoxicity or glucolipotoxicity, and the regeneration mechanism of new beta cells that will replace dead beta cells is still not fully understood. The aim of this study was to investigate the generation mechanism of new beta cells by considering the compensation phase of type 2 diabetes mellitus. In this study, pancreatic islet derived mesenchymal stem cells (PI-MSCs) were isolated from adult rats and characterized. Then, beta cells isolated from rats were co-cultured with PI-MSCs and they were exposed to glucotoxicity, lipotoxicity and glucolipotoxicity conditions for 72 hr. As the results apoptotic and necrotic cell death were increased in both PI-MSCs and beta cells especially by the exposure of glucotoxic and glucolipotoxic conditions to the co-culture systems. Glucotoxicity induced-differentiated beta cells were functional due to their capability of insulin secretion in response to rising glucose concentrations. Moreover, beta cell proliferation was induced in the glucotoxicity-treated co-culture system whereas suppressed in lipotoxicity or glucolipotoxicity-treated co-culture systems. In addition, 11 novel proteins, that may release from dead beta cells and have the ability to stimulate PI-MSCs in the direction of differentiation, were determined in media of glucotoxicity or glucolipotoxicity-treated co-culture systems. In conclusion, these molecules were considered as important for understanding cellular mechanism of beta cell differentiation and diabetes. Thus, they may be potential targets for diagnosis and cellular or therapeutic treatment of diabetes.

Elevated Serum Level of Cytokeratin 18 M65ED Is an Independent Indicator of Cardiometabolic Disorders

“…CK18 M65ED can act as a cell death marker in cardiometabolic disorders because of its ability to detect both native and intact CK18 [18]. Previous studies have demonstrated that apoptosis can cause a decrease in the number of circulating mucosalassociated invariant T cells in cardiometabolic diseases [7]. Moreover, myocardial cells undergo death in obesityassociated cardiomyopathy in high-fat diet-fed mice [8].…”

“…Journal of Diabetes Research proportion of regulatory T cells within the gut [43]. Touch et al have suggested that apoptosis of mucosal-associated invariant T cells in patients with cardiometabolic disorders occurs due to gut microbiome dysbiosis and enhanced proapoptotic signaling, which is caused by long-term and low-grade systemic inflammation [7]. The pathway in which CK18 is involved in cell death at a molecular level is, however, not very clear.…”

“…can help to get rid of damaged cells and protect cell integrity when a cell responds to the aberrant cellular stresses like endoplasmic reticulum (ER) stress and oxidative stress, which have been the hallmarks of cardiometabolic disorders [3][4][5]. Massive beta cell death [6,7] and cell death-induced decrease in the delta cell volume and number cause T2D [8]. Endothelial apoptosis can lead to endothelial dysfunction and development of hypertension [9].…”

miR‐375 induces adipogenesis through targeting Erk1 in pancreatic duct cells under the influence of sodium palmitate

“…The differentiation capacity of ARIP cells to pancreatic β‐cells and adipocytes was checked by application of differentiation protocols published before (Gezginci‐Oktayoglu et al, 2018). Briefly, for β‐cell differentiation ARIP cells were cultured with 10 mM nicotinamide, 1 mM mercaptoethanol in Dulbecco's modified Eagle's medium (DMEM) with 5.5 mM glucose for 24 h and then the same content was applied in DMEM with 25 mM glucose for 24 h under standard culture conditions.…”

Flavanonas de Citrus - mecanismos de proteção de células β-pancreáticas submetidas ao estresse oxidativo

“…Ainda, mudanças metabólicas nas células β-pancreáticas também podem ocorrer como resposta a diversos agentes estressores. Em apoptose de células β primárias, além de insulina, onze novas Cholesterol proteínas foram secretadas, entre elas a alfa-1-glicoproteína ácida (AGP), enzima aldolase frutose 1,6 bifosfato, STAM-binding protein, Interleukin-1-receptor-like 1 (IL1RL1) e brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1) (Gezginci-Oktayoglu et al, 2018). Ainda, em ilhotas pancreáticas apresentando disfunção na secreção de insulina e comprometimento da atividade oxidoredutase, identificou-se 262 proteínas secretadas, incluindo a AGP e a enzima aldolase frutose 1,6 bifosfato, bem como proteína ligadora de ácidos graxos, anexina A5 e glutationa peroxidase 1 (Kuo et al, 2016).…”