Stearoyl-CoA desaturase 1 activity determines the maintenance of DNMT1-mediated DNA methylation patterns in pancreatic β\beta-Cells

Metabolic stress, such as lipotoxicity, affects the DNA methylation profile in pancreatic β-cells and thus contributes to β-cell failure and the progression of type 2 diabetes (T2D). Stearoyl-CoA desaturase 1 (SCD1) is a rate-limiting enzyme that is involved in monounsaturated fatty acid synthesis, which protects pancreatic β-cells against lipotoxicity. The present study found that SCD1 is also required for the establishment and maintenance of DNA methylation patterns in β-cells. We showed that SCD1 inhibition/deficiency caused DNA hypomethylation and changed the methyl group distribution within chromosomes in β-cells. Lower levels of DNA methylation in SCD1-deficient β-cells were followed by lower levels of DNA methyltransferase 1 (DNMT1). We also found that the downregulation of SCD1 in pancreatic β-cells led to the activation of adenosine monophosphate-activated protein kinase (AMPK) and an increase in the activity of the NAD-dependent deacetylase sirtuin-1 (SIRT1). Furthermore, the physical association between DNMT1 and SIRT1 stimulated the deacetylation of DNMT1 under conditions of SCD1 inhibition/downregulation, suggesting a mechanism by which SCD1 exerts control over DNMT1. We also found that SCD1-deficient β-cells that were treated with compound c, an inhibitor of AMPK, were characterized by higher levels of both global DNA methylation and DNMT1 protein expression compared with untreated cells. Therefore, we found that activation of the AMPK/SIRT1 signaling pathway mediates the effect of SCD1 inhibition/deficiency on DNA methylation status in pancreatic β-cells. Altogether, these findings suggest that SCD1 is a gatekeeper that protects β-cells against the lipid-derived loss of DNA methylation and provide mechanistic insights into the mechanism by which SCD1 regulates DNA methylation patterns in β-cells and T2D-relevant tissues

Fat and Sugar—A Dangerous Duet. A Comparative Review on Metabolic Remodeling in Rodent Models of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a common disease in Western society and ranges from steatosis to steatohepatitis to end-stage liver disease such as cirrhosis and hepatocellular carcinoma. The molecular mechanisms that are involved in the progression of steatosis to more severe liver damage in patients are not fully understood. A deeper investigation of NAFLD pathogenesis is possible due to the many different animal models developed recently. In this review, we present a comparative overview of the most common dietary NAFLD rodent models with respect to their metabolic phenotype and morphological manifestation. Moreover, we describe similarities and controversies concerning the effect of NAFLD-inducing diets on mitochondria as well as mitochondria-derived oxidative stress in the progression of NAFLD

Wiedza pielęgniarek na temat odpowiedzialności zawodowej

Wstęp. Odpowiedzialność zawodowa, etyka, kompetencje zawodowe pielęgniarek to tematy budzące coraz większe zainteresowanie. Tematyka ta obejmuje świadomość odpowiedzialności wśród pielęgniarek, znajomość przez nie swoich kompetencji zawodowych, stopień zrozumienia powierzonych zadań oraz odpowiedzialność w realizowaniu standardów.Cel pracy. Celem badań była próba oceny wiedzy pielęgniarek na temat odpowiedzialności zawodowej.Materiał i metody. Badania kwestionariuszowe przeprowadzono wśród 486 pielęgniarek zatrudnionych w szpitalach znajdujących się na terenie aglomeracji śląskiej.Wyniki. Blisko 80% badanych wiedziało, że odpowiedzialność zawodową ponosi się przed sądami pielęgniarek i położnych. Prawie połowa wykazała się znajomością aktu prawnego regulującego zakres i rodzaj świadczeń wykonywanych samodzielnie przez pielęgniarkę/położną. Tylko 39% ankietowanych uczestniczyło w szkoleniach na temat odpowiedzialności zawodowej i jednocześnie 88% wyraziło chęć wzięcia udziału w takich kursach. Ponad połowa (61%) respondentów wiedziała, że może odmówić wykonania zlecenia lekarskiego.Wnioski. Wiedza badanych pielęgniarek w zakresie odpowiedzialności zawodowej jest niepełna i fragmentaryczna, co potwierdziła niska samoocena posiadanej wiedzy oraz ogromna chęć uczestnictwa w szkoleniach z tego zakresu. Badania wskazały konieczność propagowania wiedzy na temat odpowiedzialności zawodowej pielęgniarek

Interaction of mitochondria with the endoplasmic reticulum and plasma membrane in calcium homeostasis, lipid trafficking and mitochondrial structure

Studying organelles in isolation has been proven to be indispensable for deciphering the underlying mechanisms of molecular cell biology. However, observing organelles in intact cells with the use of microscopic techniques reveals a new set of different junctions and contact sites between them that contribute to the control and regulation of various cellular processes, such as calcium and lipid exchange or structural reorganization of the mitochondrial network. In recent years, many studies focused their attention on the structure and function of contacts between mitochondria and other organelles. From these studies, findings emerged showing that these contacts are involved in various processes, such as lipid synthesis and trafficking, modulation of mitochondrial morphology, endoplasmic reticulum (ER) stress, apoptosis, autophagy, inflammation and Ca2+handling. In this review, we focused on the physical interactions of mitochondria with the endoplasmic reticulum and plasma membrane and summarized present knowledge regarding the role of mitochondria-associated membranes in calcium homeostasis and lipid metabolism

Independent Factors of Changes of Ankle-Brachial Index in Peripheral Arterial Occlusive Disease in Elderly Patients with or without Diabetes

Peripheral arterial disease (PAD) belongs to the commonly-occurring pathologies associated with elderly age. A simple tool for defining the severity of PAD is the ankle-brachial index (ABI). The purpose of this research was to determine independent factors of changes of ABI in elderly patients with occlusive PAD disease (PAOD) with and without diabetes. The research was carried out on 49 elderly patients with PAOD, including 29 patients with type 2 diabetes, and 20 patients without diabetes. The concentration of interleukin-6 (IL-6), E-selectin, fibrinogen, and C-reactive protein (CRP) in the blood serum was marked. In all patients, the independent factors of changes of ABI were determined with the use of the multiple logistic regression analysis. Our results show that in the group of patients with PAOD suffering from diabetes, it was demonstrated that the ABI was related to age, the duration of the symptoms of PAD, body mass index (BMI), low-density lipoprotein cholesterol, fibrinogen, and sex (determination coefficient R2 = 0.699). In patients with PAOD without diabetes, the ABI was related to age, the duration of the symptoms of PAD, the levels of CRP, E-selectin, high-density lipoprotein cholesterol, and the glomerular filtration rate(determination coefficient R2 = 0.844). We conclude that in elderly patients with PAOD with and without diabetes, the participation of independent factors related to the ABI is diversified; in patients with diabetes, the concentration of IL-6 and fibrinogen is lower, and the concentration of E-selectin is higher than in patients without diabetes