scholarly journals Zsírsavtúltengés – inzulinrezisztencia és β-sejt-halál

2016 ◽  
Vol 157 (19) ◽  
pp. 733-739 ◽  
Author(s):  
Miklós Csala
Keyword(s):  
Fatty Acids ◽  
Insulin Signaling ◽  
Cell Damage ◽  
Local Inflammation ◽  
Cellular Functions ◽  
Β Cell ◽  
The Metabolic Syndrome ◽  
Rapid Spread ◽  
New Strategies

The increasing prevalence of type 2 diabetes correlates with the rapid spread of obesity worldwide. Adipocytes are strained by the demand of excessive storage, and the local inflammation accelerates triglyceride turnover, which elevates the plasma levels of free fatty acids. Sustained hyper-free fatty acidemia leads to disturbances in cellular functions (lipotoxicity) or even to programmed cell death. Activated stress kinases interfere with insulin signaling, and often facilitate apoptosis. Hyper-free fatty acidemia, therefore, links obesity to diabetes through insulin resistance and β-cell damage. Lipotoxicity research – including the comparison of the effects exerted by saturated, unsaturated and trans fatty acids – provides explanations for long-known phenomena. Our widening knowledge in the field offers new strategies for prevention and treatment of the metabolic syndrome and diabetes. Orv. Hetil., 2016, 157(19), 733–739.

Effects of palmitate on ER and cytosolic Ca2+ homeostasis in β-cells

2009 ◽  
Vol 296 (4) ◽  
pp. E690-E701 ◽  
Author(s):  
Kamila S. Gwiazda ◽  
Ting-Lin B. Yang ◽  
Yalin Lin ◽  
James D. Johnson
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Cell Function ◽  
Fluorescent Protein ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function

There are strong links between obesity, elevated free fatty acids, and type 2 diabetes. Specifically, the saturated fatty acid palmitate has pleiotropic effects on β-cell function and survival. In the present study, we sought to determine the mechanism by which palmitate affects intracellular Ca2+, and in particular the role of the endoplasmic reticulum (ER). In human β-cells and MIN6 cells, palmitate rapidly increased cytosolic Ca2+ through a combination of Ca2+ store release and extracellular Ca2+ influx. Palmitate caused a reversible lowering of ER Ca2+, measured directly with the fluorescent protein-based ER Ca2+ sensor D1ER. Using another genetically encoded indicator, we observed long-lasting oscillations of cytosolic Ca2+ in palmitate-treated cells. In keeping with this observed ER Ca2+ depletion, palmitate induced rapid phosphorylation of the ER Ca2+ sensor protein kinase R-like ER kinase (PERK) and subsequently ER stress and β-cell death. We detected little palmitate-induced insulin secretion, suggesting that these Ca2+ signals are poorly coupled to exocytosis. In summary, we have characterized Ca2+-dependent mechanisms involved in altered β-cell function and survival induced by the free fatty acid palmitate. We present the first direct evidence that free fatty acids reduce ER Ca2+ and shed light on pathways involved in lipotoxicity and the pathogenesis of type 2 diabetes.

Ketosis-Prone Type 2 Diabetes: Effect of Hyperglycemia on β-Cell Function and Skeletal Muscle Insulin Signaling

2007 ◽  
Vol 13 (3) ◽  
pp. 283-290 ◽  
Author(s):  
Guillermo Umpierrez ◽  
Dawn Smiley ◽  
Aidar Gosmanov ◽  
Donald Thomason
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Insulin Signaling ◽  
Cell Function ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Effect of Hydrolyzed Bird’s Nest on β-Cell Function and Insulin Signaling in Type 2 Diabetic Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Ker Woon Choy ◽  
Zuhaida Md Zain ◽  
Dharmani Devi Murugan ◽  
Nelli Giribabu ◽  
Nor Hisam Zamakshshari ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Cell Function ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Diabetic Mice ◽  
Β Cell ◽  
Β Cell Function ◽  
Type 2 Diabetic ◽  
Pro Inflammatory Cytokines

Type 2 diabetes mellitus is characterized by both resistance to the action of insulin and defects in insulin secretion. Bird’s nest, which is derived from the saliva of swiftlets are well known to possess multiple health benefits dating back to Imperial China. However, it’s effect on diabetes mellitus and influence on the actions of insulin action remains to be investigated. In the present study, the effect of standardized aqueous extract of hydrolyzed edible bird nest (HBN) on metabolic characteristics and insulin signaling pathway in pancreas, liver and skeletal muscle of db/db, a type 2 diabetic mice model was investigated. Male db/db diabetic and its euglycemic control, C57BL/6J mice were administered HBN (75 and 150 mg/kg) or glibenclamide (1 mg/kg) orally for 28 days. Metabolic parameters were evaluated by measuring fasting blood glucose, serum insulin and oral glucose tolerance test (OGTT). Insulin signaling and activation of inflammatory pathways in liver, adipose, pancreas and muscle tissue were evaluated by Western blotting and immunohistochemistry. Pro-inflammatory cytokines were measured in the serum at the end of the treatment. The results showed that db/db mice treated with HBN significantly reversed the elevated fasting blood glucose, serum insulin, serum pro-inflammatory cytokines levels and the impaired OGTT without affecting the body weight of the mice in all groups. Furthermore, HBN treatment significantly ameliorated pathological changes and increased the protein expression of insulin, and glucose transporters in the pancreatic islets (GLUT-2), liver and skeletal muscle (GLUT-4). Likewise, the Western blots analysis denotes improved insulin signaling and antioxidant enzyme, decreased reactive oxygen species producing enzymes and inflammatory molecules in the liver and adipose tissues of HBN treated diabetic mice. These results suggest that HBN improves β-cell function and insulin signaling by attenuation of oxidative stress mediated chronic inflammation in the type 2 diabetic mice.

scholarly journals Sphingosine-1-Phosphate Metabolism in the Regulation of Obesity/Type 2 Diabetes

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1682
Author(s):  
Jeanne Guitton ◽  
Cécile L. Bandet ◽  
Mohamed L. Mariko ◽  
Sophie Tan-Chen ◽  
Olivier Bourron ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Signaling ◽  
Current Knowledge ◽  
Sphingolipid Metabolism ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Sphingosine 1 Phosphate

Obesity is a pathophysiological condition where excess free fatty acids (FFA) target and promote the dysfunctioning of insulin sensitive tissues and of pancreatic β cells. This leads to the dysregulation of glucose homeostasis, which culminates in the onset of type 2 diabetes (T2D). FFA, which accumulate in these tissues, are metabolized as lipid derivatives such as ceramide, and the ectopic accumulation of the latter has been shown to lead to lipotoxicity. Ceramide is an active lipid that inhibits the insulin signaling pathway as well as inducing pancreatic β cell death. In mammals, ceramide is a key lipid intermediate for sphingolipid metabolism as is sphingosine-1-phosphate (S1P). S1P levels have also been associated with the development of obesity and T2D. In this review, the current knowledge on S1P metabolism in regulating insulin signaling in pancreatic β cell fate and in the regulation of feeding by the hypothalamus in the context of obesity and T2D is summarized. It demonstrates that S1P can display opposite effects on insulin sensitive tissues and pancreatic β cells, which depends on its origin or its degradation pathway.

From Obesity to Diabetes

2006 ◽  
Vol 76 (4) ◽  
pp. 172-177 ◽  
Author(s):  
Keller
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Free Fatty Acids ◽  
Vegetable Consumption ◽  
Prediabetic State ◽  
The Metabolic Syndrome ◽  
Life Style Changes

The prevalence of obesity has been increasing dramatically in the last decades in the whole world, not only in industrialized countries but also in developing areas. A major complication of obesity is insulin resistance and type 2 diabetes. Diabetes is also rapidly increasing world-wide – reaching a prevalence in adults of approx. 5–6% in Central Europe and in the US, and more than 50% in specific, genetically prone populations. This article reviews pathogenetic mechanisms linking obesity and type 2 diabetes. Emphasis is placed on the observation that excessive amounts of adipocytes are associated with an impairment of insulin sensitivity, a key feature of the "metabolic syndrome". This is a cluster of metabolic abnormalities such as type 2 diabetes, hypertension and dyslipidemia; all of them are enhanced by the presence of visceral (abdominal) obesity and all contribute to the increased cardiovascular risk observed in these patients. Besides release of free fatty acids, adipocytes secrete substances that contribute to peripheral insulin resistance, including adiponectin, resistin, TNF-α and interleukin 6. Increased turnover of free fatty acids interferes with intracellular metabolism of glucose in the muscle, and they exert lipotoxic effect on pancreatic β-cells. The pre-receptor metabolism of cortisol is enhanced in visceral adipose tissue by activation of 11 β-hydroxysteroid dehydrogenase type 1. A new class of anti-diabetic drugs (thiazolidinediones, or glitazones) bind to peroxisome proliferator activated receptor (PPAR-γ) and lower thereby plasma free fatty acids and cytokine production in adipocytes, in addition to a decrease of resistin and an increase in adiponectin observed in animals, resulting in an overall increase in insulin sensitivity and in an improvement of glucose homeostasis. However, the first step to avoid insulin resistance and prevent the development of diabetes should be a reduction in body weight in overweight subjecs, and an increase in physical activity. There are now three published randomized controlled trials demonstrating that in high risk individuals, life style changes with modest weight lost, associated with diminished fat intake and an increase in fruit and vegetable consumption result in marked inhibition of the transition from the prediabetic state to manifest type 2 diabetes.

An overview of dietary supplements on obesity and type 2 diabetes: efficacy and mechanisms

2021 ◽  
Vol 22 ◽  
Author(s):  
Xiaohong Liu ◽  
Xin Zeng ◽  
Wen Liu ◽  
Yanrong Lu ◽  
Jingqiu Cheng ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Dietary Supplements ◽  
Unsaturated Fatty Acids ◽  
Biological Activities ◽  
Dietary Factors ◽  
Dietary Therapy ◽  
Β Cell ◽  
Bioactive Ingredients

: Obesity is a common nutritional disorder, associated with a variety of chronic diseases, among them, type 2 diabetes (T2DM) has emerged as a serious worldwide health problem. Insulin resistance and β cell dysfunction are the main pathological characteristics of T2DM, and obesity and hyperlipidemia are the critical causal factors. It is commonly accepted that dietary factors are of paramount importance in the management of obesity and T2DM. Particularly, many botanic products and their extracts are endowed with a wide spectrum of biological activities, making them extensively studied as anti-obesity and anti-diabetes dietary supplements or new drug candidates. In this review, we aimed to summarize the effects, related mechanisms, and safety issues of dietary continents on obesity and T2DM, to provide theoretical support for better research and development of dietary therapy strategy for the treatment of obesity and T2DM. Based on a bunch of clinical investigations, specific carbohydrates and fatty acids, such as dietary fibers, polysaccharides, unsaturated fatty acids, have hypoglycemic and hypolipidemic effects. Vitamin D plays important role in metabolism and immunity modulation. Apart from them, natural bioactive ingredients from plants, such as flavonoids, polyphenols, alkaloids, terpenoids, polysaccharides, and quinones are efficient in helping weight loss and improving insulin sensitivity and glycemic control. They can protect β cell function by anti-inflammation, anti-oxidation, and anti-apoptosis properties, as well as regulating lipid metabolism. Therefore, promoting the consumption of diverse natural bioactive ingredients-rich products could be an effective nutritional strategy to benefit patients with obesity and type 2 diabetes.

scholarly journals Herbal constituent sequoyitol improves hyperglycemia and glucose intolerance by targeting hepatocytes, adipocytes, and β-cells

2012 ◽  
Vol 302 (8) ◽  
pp. E932-E940 ◽  
Author(s):  
Hong Shen ◽  
Mengle Shao ◽  
Kae Won Cho ◽  
Suqing Wang ◽  
Zheng Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glucose Intolerance ◽  
Insulin Signaling ◽  
Glucose Production ◽  
Water Soluble ◽  
Β Cells ◽  
Β Cell ◽  
Reduce Blood Glucose

The prevalence of insulin resistance and type 2 diabetes increases rapidly; however, treatments are limited. Various herbal extracts have been reported to reduce blood glucose in animals with either genetic or dietary type 2 diabetes; however, plant extracts are extremely complex, and leading compounds remain largely unknown. Here we show that 5- O-methyl- myo-inositol (also called sequoyitol), a herbal constituent, exerts antidiabetic effects in mice. Sequoyitol was chronically administrated into ob/ob mice either orally or subcutaneously. Both oral and subcutaneous administrations of sequoyitol decreased blood glucose, improved glucose intolerance, and enhanced insulin signaling in ob/ob mice. Sequoyitol directly enhanced insulin signaling, including phosphorylation of insulin receptor substrate-1 and Akt, in both HepG2 cells (derived from human hepatocytes) and 3T3-L1 adipocytes. In agreement, sequoyitol increased the ability of insulin to suppress glucose production in primary hepatocytes and to stimulate glucose uptake into primary adipocytes. Furthermore, sequoyitol improved insulin signaling in INS-1 cells (a rat β-cell line) and protected INS-1 cells from streptozotocin- or H2O2-induced injury. In mice with streptozotocin-induced β-cell deficiency, sequoyitol treatments increased plasma insulin levels and decreased hyperglycemia and glucose intolerance. These results indicate that sequoyitol, a natural, water-soluble small molecule, ameliorates hyperglycemia and glucose intolerance by increasing both insulin sensitivity and insulin secretion. Sequoyitol appears to directly target hepatocytes, adipocytes, and β-cells. Therefore, sequoyitol may serve as a new oral diabetes medication.

Regulating insulin signaling and β-cell function through IRS proteinsThis paper is one of a selection of papers published in this Special Issue, entitled Second Messengers and Phosphoproteins—12th International Conference.

2006 ◽  
Vol 84 (7) ◽  
pp. 725-737 ◽  
Author(s):  
Morris F. White
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Signaling ◽  
Cell Function ◽  
Second Messengers ◽  
Glucose Sensing ◽  
Β Cell ◽  
Peripheral Insulin Resistance ◽  
Chronic Hyperglycemia

Diabetes mellitus is a complex disorder that arises from various causes, including dysregulated glucose sensing and impaired insulin secretion (maturity onset diabetes of youth, MODY), autoimmune-mediated β-cell destruction (type 1), or insufficient compensation for peripheral insulin resistance (type 2). Type 2 diabetes is the most prevalent form that usually occurs at middle age; it afflicts more than 30 million people over the age of 65, but is appearing with greater frequency in children and adolescents. Dysregulated insulin signaling exacerbated by chronic hyperglycemia promotes a cohort of systemic disorders—including dyslipidemia, hypertension, cardiovascular disease, and female infertility. Understanding the molecular basis of insulin resistance can prevent these disorders and their inevitable progression to type 2 diabetes.

n-3 Polyunsaturated fatty acids protect against pancreatic β-cell damage due to ER stress and prevent diabetes development

2015 ◽  
Vol 59 (9) ◽  
pp. 1791-1802 ◽  
Author(s):  
Jie Wang ◽  
Mi-Young Song ◽  
Ui-Jin Bae ◽  
Jung Min Lim ◽  
Keun Sang Kwon ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Er Stress ◽  
Cell Damage ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Diabetes Development
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