Diabetes and associated cardiovascular complications: The role of microRNAs

Diabetes mellitus (DM) refers to a complex cluster of metabolic disorders characterized by hyperglycemia caused by inadequate insulin secretion, insulin resistance, or excessive glucagon secretion. If not correctly treated, the prolonged effects of DM-associated metabolic perturbations lead to systemic vascular complications and cardiovascular disease (CVD), the principal cause of mortality among patients with DM. Given the increase in the global prevalence of diabetes, novel diagnostic and therapeutic procedures are necessary for its effective identification and treatment. Recent findings point to an important role of microRNA (miRNAs) in DM initiation and progression, as well as the occurrence of associated cardiovascular complications. miRNAs are short, highly conserved, single-stranded, non-coding RNAs that contribute to the maintenance of physiological homeostasis through the regulation of crucial processes such as metabolism, cell proliferation, and apoptosis. The increased availability of high-throughput methodologies for identifying and characterizing non-coding RNAs has led to considerable interest in miRNAs as potential biomarkers and therapeutic agents for DM. In this review, we first comprehensively detail the regulatory miRNAs involved in the pathophysiology of DM and diabetic cardiomyopathy (DCMP). Subsequently, we summarize findings regarding the utility of several of these miRNAs as potential prognostic and diagnostic biomarkers for DM and DM-associated CVD. Finally, we evaluate the potential of miRNA-based therapeutic approaches for treating DM and DCMP in the clinical setting

Editorial: Oxidative stress and inflammation in cardiometabolic disorders

Editorial on the Research Topic: Oxidative stress and inflammation in cardiometabolic disorder

Novel insights regarding the role of noncoding RNAs in diabetes

Diabetes mellitus (DM) is a group of metabolic disorders defined by hyperglycemia induced by insulin resistance, inadequate insulin secretion, or excessive glucagon secretion. In 2021, the global prevalence of diabetes is anticipated to be 10.7% (537 million people). Noncoding RNAs (ncRNAs) appear to have an important role in the initiation and progression of DM, according to a growing body of research. The two major groups of ncRNAs implicated in diabetic disorders are miRNAs and long noncoding RNAs. miRNAs are singlestranded, short (17–25 nucleotides), ncRNAs that influence gene expression at the post-transcriptional level. Because DM has reached epidemic proportions worldwide, it appears that novel diagnostic and therapeutic strategies are required to identify and treat complications associated with these diseases efficiently. miRNAs are gaining attention as biomarkers for DM diagnosis and potential treatment due to their function in maintaining physiological homeostasis via gene expression regulation. In this review, we address the issue of the gradually expanding global prevalence of DM by presenting a complete and upto-date synopsis of various regulatory miRNAs involved in these disorders. We hope this review will spark discussion about ncRNAs as prognostic biomarkers and therapeutic tools for DM. We examine and synthesize recent research that used novel, high-throughput technologies to uncover ncRNAs involved in DM, necessitating a systematic approach to examining and summarizing their roles and possible diagnostic and therapeutic uses

Effect of acute adrenalectomy on rat liver glucocorticoid receptor

In order to improve current clinical treatment of human hypocortisolism, it is necessary to understand molecular aspects of this pathophysiology. In this study liver tissues from male Wistar rats were used as an experimental model to study structural and functional properties of glucocorticoid receptor (GR) in the absence of glucocorticoid hormones (GC). Results show that acute adrenalectomy (ADX) significantly increases the number of GR binding sites and GR protein content. In addition, acute ADX stimulates increase in stability of the GR, decrease in stability of the glucocorticoid- receptor complex (G-R), and changes in accumulation of the G-R complex in nuclei and its cellular distribution.

Non-alcoholic fatty liver disease: a multidisciplinary clinical practice approach—the institutional adaptation to existing Clinical Practice Guidelines

Non-alcoholic fatty liver disease (NAFLD) is among the most frequently encountered chronic liver diseases in everyday clinical practice. It is considered the hepatic manifestation of metabolic syndrome. Today, liver biopsy is still the gold standard for NAFLD confirmation and assessing NAFLD's possible progression to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Because of the high prevalence of NAFLD and potential associated risks of invasive diagnostic procedures, it is of great interest to recruit the patients for liver biopsy. However, as the presence of liver fibrosis determines the further clinical course, liver biopsy is expectedly reserved for those with increased fibrosis risk. The quality of liver biopsy recruitment and patient monitoring could be significantly improved by using non-invasive tools to assess liver fibrosis presence and interactive collaboration between general practitioners, gastroenterologists, and endocrinologists. As a result, the quality of liver biopsy recruitment and patients monitoring could be significantly improved. Here, we proposed clinical practice guidelines that could be implemented for everyday clinical practice in NAFLD patients

The role of G protein coupled receptor kinases in neurocardiovascular pathophysiology

In coronary artery disease the G protein related kinases (GRKs) play a role in desensitization of beta-adrenoreceptors (AR) after coronary occlusion. Targeted deletion and lowering of cardiac myocyte GRK-2 decreases the risk of post-ischemic heart failure (HF). Studies carried out in humans confirm the role of GRK-2 as a marker for the progression of HF after myocardial infarction (MI). The level of GRK-2 could be an indicator of beta-AR blocker efficacy in patients with acute coronary syndrome. Elevated levels of GRK-2 are an early ubiquitous consequence of myocardial injury. In hypertension an increased level of GRK-2 was reported in both animal models and human studies. The role of GRKs in vagally mediated disorders such as vasovagal syncope and atrial fibrillation remains controversial. The role of GRKs in the pathogenesis of neurocardiological diseases provides an insight into the molecular pathogenesis process, opens potential therapeutic options and suggests new directions for scientific research

The relationship between vitamin D and obesity

Currently, vitamin D deficiency and obesity are pandemic diseases and they are associated with cardiovascular (CV) disease, metabolic syndrome and type 2 diabetes mellitus (T2DM) and other diseases. Concentrations of 25-hydroxyvitamin D (25(OH) D) (25D) are considered as the best indicator of total body vitamin D stores. An association between reduced circulating 25D concentrations and obesity is well known, but the mechanisms are not totally clear. The role of vitamin D supplementation is still uncertain and prospective interventions will establish its influence, if any, in the treatment of obesity. Vitamin D deficiency is associated with the presence of a cardiometabolic risk profile in the obese. Future trials may establish a role for Vitamin D supplementation in individuals at increased CV risk

The impact of obesity on development of cardiovascular diseases: Mini review

Prekomerno prisustvo adipoznog tkiva u organizmu, odnosno gojaznost, predstavlja rezultat energetskog disbalansa, pri čemu unos energije premašuje energetsku potrošnju tokom vremena. Gojaznost se smatra hroničnim metaboličkim poremećajem povezanim sa hroničnom niskom inflamacijom okarakterisanom značajnim promenama nivoa adipokina i proinflamatornih citokina, kao i drugih molekula koji utiču na kardiovaskularnu funkciju. Stoga se gojaznost, posebno centralna gojaznost, smatra značajnim faktorom rizika za nastanak kardiovaskularnih bolesti (KVB), među kojima su ateroskleroza i bolest koronarnih arterija, hipertenzija i disfunkcija leve komore. Povećano nakupljanje masnog tkiva oko srca i krvnih sudova, povećani nivo oksidativnog stresa i inflamatorno stanje međusobno interaguju u procesu nastanka KVB. Smanjenje telesne težine može značajno doprineti smanjenju KVB i njihovih komplikacija. U okviru ovog kratkog preglednog članka, dat je prikaz najnovijih literaturnih podataka o uticaju gojaznosti na nastanak kardiovaskularnih poremećaja.Obesity is considered to be a chronic metabolic disorder closely connected to the chronically low inflammation characterized by significant changes in the levels of adipokines and proinflammatory cytokines, as well as other molecules that have an impact on cardiovascular function. Therefore, obesity (especially central obesity) is considered to be a significant risk factor for the development of cardiovascular diseases, atherosclerosis, coronary artery disease, hypertension and left ventricular dysfunction being some of them. The increased accumulation of fat tissue around the heart and in the blood vessels, the increased levels of oxidative stress and the inflammatory state mutually interact in the process of cardiovascular disease occurrence. Lowering the amount of body weight could significantly contribute to reduction of cardiovascular diseases and the subsequent complications

Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU145 human prostate cancer cells

Gamma-irradiation (gamma-IR) is extensively used in the treatment of hormone-resistant prostate carcinoma. The objective of the present study was to investigate the effects of Co-60 gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl)-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD), specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. gamma-IR treatment had a significant (P lt 0.001) antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose of gamma-IR which inhibited DNA synthesis and cell proliferation by 50% was 9.7 Gy. Furthermore, gamma-IR induced cell cycle arrest in the G2/M phase and the percentage of cells in the G2/M phase was increased from 15% (control) to 49% (IR cells), with a nonsignificant induction of apoptosis. Treatment with 10 Gy gamma-IR for 24, 48, and 72 h stimulated CuZnSOD and MnSOD protein expression in a time-dependent manner, approximately by 3- to 3.5-fold. These data suggest that CuZnSOD and MnSOD enzymes may play an important role in the gamma-IR-induced changes in DU 145 cell growth, cell cycle arrest and cell death

Leptin and its mechanism of action

Leptin je hormon adipoznog tkiva koji svoje efekte ostvaruje delovanjem na centralni nervni sistem. Leptin se vezuje za svoje OB receptore na neuronima hipotalamusa i posledično suprimira unos hrane i povećava aktivnost simpatičkog nervnog sistema čime stimuliše proces termogeneze i potrošnje energije. Osim što suprimira apetit i stimuliše termogenu potrošnju energije, leptin ostvaruje svoje efekte i na druge organske sisteme, kao što su endokrini, vaskularni, hematopoetski, imunski i mišićnoskeletni, delujući bilo direktno na periferiji organizma, bilo posredstvom centralnog nervnog sistema. Svoje efekte leptin ostvaruje putem veoma rasprostranjene mreže leptinskih receptora, preko nekoliko različitih molekularnih signalnih puteva. Stanje gojaznosti je praćeno povećanjem nivoa leptina u cirkulaciji usled povećane količine masnog tkiva, ali i pored toga, gojazne osobe ispoljavaju rezistenciju na anoreksigenične i metaboličke efekte leptina. Izvestan broj studija je pokazao da leptin može povećati aktivnost simpatičkog nervnog sistema i u netermogenim tkivima glodara dovodeći do hipertenzije usled gojaznosti. Koncept selektivne rezistenicije na leptin predstavlja moguće objašnjenje ovog paradoksa. Još uvek su malobrojne studije u kojima je ispitivan fenomen selektivne leptinske rezistencije kod ljudi. U okviru ovog preglednog članka, dat je prikaz najnovijih saznanja o leptinu, mehanizmu njegovog delovanja kao i o ulozi leptina u patofiziološkim stanjima.Leptin is a hormone produced by the adipose tissue, which has effects on the central nervous system. Leptin is bound to its Ob receptor on hypo-thalamic neurons to inhibit feeding behavior and to increase sympathetically-mediated thermogenesis. In addition to anorexia and thermogenesis, leptin also has direct peripheral and central nervous system-mediated effects on the endocrine, vascular, hematopoietc, immune and musculoskeletal systems. Leptin accomplishes its effects using distributed network of leptin receptors and differential molecular signaling pathways. Leptinemia is increased in obesity because of increased adipocyte mass, but obese subjects exhibit resistance to the anorexic and metabolic effects of leptin. However, multiple studies have shown that leptin can increase sympathetic nerve activity to non-thermogenic tissues in rodents causing obesity-related hypertension. One potential explanation of this paradox is selective leptin resistance. Compared with large and persuasive number of studies on the sympathetic and blood pressure effects of leptin in experimental animals, relatively little attention was given to these effects of leptin in humans. This review article presents recent findings related to leptin and its mechanism of action, and also the role of leptin in patophysiological conditions