scholarly journals Role of small leucine zipper protein in hepatic gluconeogenesis and metabolic disorder

Author(s):  
Minsoo Kang ◽  
Sun Kyoung Han ◽  
Suhyun Kim ◽  
Sungyeon Park ◽  
Yerin Jo ◽  
...  

Abstract Hepatic gluconeogenesis is the central pathway for glucose generation in the body. The imbalance between glucose synthesis and uptake leads to metabolic diseases such as obesity, diabetes, and cardiovascular diseases. Small leucine zipper protein (sLZIP) is an isoform of LZIP and it mainly functions as a transcription factor. Although sLZIP is known to regulate the transcription of genes involved in various cellular processes, the role of sLZIP in hepatic glucose metabolism is not known. In this study, we investigated the regulatory role of sLZIP in hepatic gluconeogenesis and its involvement in metabolic disorder. We found that sLZIP expression was elevated during glucose starvation, leading to the promotion of phosphoenolpyruvate carboxylase and glucose-6-phosphatase expression in hepatocytes. However, sLZIP knockdown suppressed the expression of the gluconeogenic enzymes under low glucose conditions. sLZIP also enhanced glucose production in the human liver cells and mouse primary hepatic cells. Fasting-induced cyclic adenosine monophosphate impeded sLZIP degradation. Results of glucose and pyruvate tolerance tests showed that sLZIP transgenic mice exhibited abnormal blood glucose metabolism. These findings suggest that sLZIP is a novel regulator of gluconeogenic enzyme expression and plays a role in blood glucose homeostasis during starvation.

2021 ◽  
Vol 11 (9) ◽  
pp. 544-549
Author(s):  
Paulina Trojanowska ◽  
Magdalena Chrościńska-Krawczyk ◽  
Alina Trojanowska ◽  
Ewa Tywanek ◽  
Jakub Wronecki ◽  
...  

Understanding the important role of the non-specific immune response in protecting the body against the development of numerous diseases has become partially possible after the discovery of several classes of pattern recognition receptors (PRR), such as Toll-like or NOD-like receptors. A group of cytoplasmic proteins called the inflammasome, which detect PAMP and DAMP through the PRR receptors, is able to activate pro-inflammatory cytokines and trigger an acute inflammatory reaction both in the extracellular and intracellular space. Low-grade systemic and local inflammation contributes to the development and progression of various conditions, including autoimmune and metabolic diseases, such as diabetes, metabolic syndrome and atherosclerosis, which until recently were not even considered inflammatory diseases. This review will discuss the role of innate immunity in the development of type 1 and type 2 diabetes, focusing on the role of specific innate immunity receptors and insulin resistance involved in these diseases pathogenesis.


Endocrine ◽  
2020 ◽  
Vol 70 (3) ◽  
pp. 629-634 ◽  
Author(s):  
Rossella Cannarella ◽  
Nicolò Musso ◽  
Rosita A. Condorelli ◽  
Marco Musmeci ◽  
Stefania Stefani ◽  
...  

Abstract Objective To assess the role of c. 2039 A/G (p. Asp680Ser) (rs6166) and c. −29 G/A (rs1394205) follicle-stimulating hormone receptor (FSHR) gene single nucleotide polymorphisms (SNPs) in a cohort of healthy men. Methods One-hundred twenty-seven healthy men underwent evaluation of the anthropometric parameters, assessment of metabolic and lipid profile, measurement FSH serum levels, and genotyping of both the aforementioned FSHR SNPs. Data grouped according to the FSHR rs6166 or rs1394205 genotypes underwent to statistical analysis. Main results The three groups of men for each FSHR SNP did not differ statistically significantly for body mass index and serum FSH levels. As for FSHR rs6166 SNP, glucose levels were significantly lower in men with the GG genotype compared with those with the AA genotype. Men with AG had lower insulin levels and HOMA index values compared with those carrying the genotype AA (p < 0.05). The GG group showed a negative correlation between serum FSH levels and insulin and between serum FSH levels and HOMA index (p < 0.05). In contrast, men grouped according to the FSHR rs1394205 genotype showed no significant difference in blood glucose, serum insulin levels, and HOMA index. The AG group showed a negative correlation between FSH insulin and between serum FSH levels and HOMA index (p < 0.05). Conclusions Men with the genotype GG of the FSHR rs6166 SNP have lower blood glucose levels than those with the AA genotype. Their FSH levels inversely correlated with insulin and HOMA index. In contrast, the genotype FSHR rs6166 A/G did not reveal any role of FSH on glucose metabolism in healthy men. The inverse relationship between FSH and insulin or HOMA index in the group with the genotype GG of the FSHR rs6166 SNP suggests a possible cross-talk between FSH and insulin.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2350-2350
Author(s):  
Zeynep Karakas ◽  
Cihangir Sevimli ◽  
Nurdan Gul ◽  
Rana Comert ◽  
Memduh Dursun

Abstract The relationship between pancreatic iron overload and glucose dysregulation has not been well defined and need further investigation. Pancreas iron load measurements are also necessary to understand how hepatic, pancreatic, and cardiac iron burden prospectively modulate the evolution of diabetes in transfusion dependent thalassemia (TDT). Aim: This study aims to evaluate the presence of pancreatic iron overload among TDT patients in Turkey based on the MRI R2* and T2* results as well as to determine its association to Fasting blood glucose (FBG), insulin, fructosamine, Homa-IR, C-peptide, ferritin, liver, cardiac and hypophysis MRI R2* results. Material and Methods: This study was conducted at the Thalassemia Center in Istanbul University, Istanbul Medical Faculty. Forty-one TDT patients included the study with a mean age of 29.9±9,9 (median 29) years old, ranging from 11 to 45 years old. Pancreatic, liver, cardiac and hypophsis MRI's were conducted using 1.5 Tesla Philips MRI machine in the Department of Radiology. Pancreatic MRI R2* results < 30 Hz were considered normal, 30-100 Hz as mild, and > 100 Hz as moderate to severe pancreatic siderosis. Pancreatic MRI T2 results >26 ms were is normal, < 10 ms is severe iron overload as presented at literature. Correlations between pancreatic MRI R2* results and FBG, insulin, fructosamine, Homa-IR, C-peptide, ferritin, cardiac and hypophysis MRI R2* were evaluated using the Pearson correlation, Man Whitney U test. Results: Laboratory findings of glucose metabolism and MRI's of liver, pancreas, hypophsis and cardiac iron are shown at Table 1. There were no significant relationship between fasting blood glucose, insülin, C-peptid level, fructosamine, Homa-IR, ferritin and Pancreas T2* and R2* results (p>0.05). There was significant correlation between liver and pancreas MRI T2* and R2* results. (p<0.01). There was no significant correlation between hypophysis global R2, cardiac R2*, Pancreas T2* and, Pancreas R2* measurements (p>0.05). Fourteen patients were found to have normal pancreatic MRI R2* (34,1%) while 19 patients have normal pancreatic MRI T2 (46.3%). It is reported that T2 is irrelevant to age and sex, and R2 can be related to age-related fatty degeneration. There was significant pancreatic iron burden in 31.7% of patients (R2*>100 Hz), of whom only 1 patient was under 18 years of age.There were 22 (53.6%) patients with T2* <26 ms and had iron overload, 13 (31.7%) had T2 <10 ms and had significant iron overload. Almost three-quarters of patients (n:13, 31.7%) had moderate to severe pancreatic iron load on both T2* and R2* measurements. Thirteen patients with significant pancreatic iron overload had 3 severe hypophysis, 1 moderate, 2 severe cardiac siderosis. and had no serious liver iron burden. This shows that the treatment of chelation first led to liver, then heart and pituitary, respectively, and finally pancreatic iron burden and demonstrates the importance of pancreas MR in assessing the body iron load. Discussion:The lack of correlation between pancreatic and cardiac MRI R2* are in contrast to another demonstrating that pancreatic iron load are good predictors of cardiac iron load. This is due to the fact that our patients are followed up with cardiac MR and taken to the intensive chelation programs of the patients who detect iron in the heart. Previous studies also report that while pancreatic R2* may be sensitive for glucose dysregulation, most patients may still have no symptoms and normal blood glucose, indicating the presence of a preclinical iron burden. Pancreatic MRI R2* can detect pancreatic iron accumulation at a much earlier stage. Lack of excessive iron load in liver of our patient can be explain low glucose metabolism disorder despite high pancreatic iron overload. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Chidiebere V. Ugwueze ◽  
Odunze J. Ogamba ◽  
Ekenechukwu E. Young ◽  
Belonwu M. Onyenekwe ◽  
Basil C. Ezeokpo

Metformin has been used for a long time as an antidiabetic medication for type 2 diabetes. It is used either as a monotherapy or in combination with other antidiabetic medications. The drug came into prominence in diabetes and other conditions with cardiovascular risk after the landmark study of 1995 by the United Kingdom Prospective Diabetes Study which emphasized its importance. However, the drug has been used in experimental trials in various aspects of medicine and pharmacology such as in reproductive medicine, cancer chemotherapy, metabolic diseases, and neurodegenerative diseases. It has been in use in the treatment of polycystic ovarian disease and obesity and is being considered in type 1 diabetes. This study seeks to evaluate the relevance of metformin in cancer management. Different mechanisms have been proposed for its antitumor action which involves the following: (a) the activation of adenosine monophosphate kinase, (b) modulation of adenosine A1 receptor (ADORA), (c) reduction in insulin/insulin growth factors, and (d) the role of metformin in the inhibition of endogenous reactive oxygen species (ROS); and its resultant damage to deoxyribonucleic acid (DNA) molecule is another paramount antitumor mechanism.


Metabolites ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 282 ◽  
Author(s):  
Fabienne Rajas ◽  
Amandine Gautier-Stein ◽  
Gilles Mithieux

Cells efficiently adjust their metabolism according to the abundance of nutrients and energy. The ability to switch cellular metabolism between anabolic and catabolic processes is critical for cell growth. Glucose-6 phosphate is the first intermediate of glucose metabolism and plays a central role in the energy metabolism of the liver. It acts as a hub to metabolically connect glycolysis, the pentose phosphate pathway, glycogen synthesis, de novo lipogenesis, and the hexosamine pathway. In this review, we describe the metabolic fate of glucose-6 phosphate in a healthy liver and the metabolic reprogramming occurring in two pathologies characterized by a deregulation of glucose homeostasis, namely type 2 diabetes, which is characterized by fasting hyperglycemia; and glycogen storage disease type I, where patients develop severe hypoglycemia during short fasting periods. In these two conditions, dysfunction of glucose metabolism results in non-alcoholic fatty liver disease, which may possibly lead to the development of hepatic tumors. Moreover, we also emphasize the role of the transcription factor carbohydrate response element-binding protein (ChREBP), known to link glucose and lipid metabolisms. In this regard, comparing these two metabolic diseases is a fruitful approach to better understand the key role of glucose-6 phosphate in liver metabolism in health and disease.


2019 ◽  
Vol 286 (1898) ◽  
pp. 20190244 ◽  
Author(s):  
Hayley A. Young ◽  
Chantelle M. Gaylor ◽  
Danielle de Kerckhove ◽  
Heather Watkins ◽  
David Benton

Recently, interoception and homeostasis have been described in terms of predictive coding and active inference. Afferent signals update prior predictions about the state of the body, and stimulate the autonomic mediation of homeostasis. Performance on tests of interoceptive accuracy (IAc) may indicate an individual's ability to assign precision to interoceptive signals, thus determining the relative influence of ascending signals and the descending prior predictions. Accordingly, individuals with high IAc should be better able to regulate during the postprandial period. One hundred females were allocated to consume glucose, an artificially sweetened drink, water or no drink. Before, and 30 min after a drink, IAc, heart rate (HR) and blood glucose (BG) were measured, and participants rated their hunger, thirst and mood. A higher IAc was related to lower BG levels, a decline in anxiety and a higher HR, after consuming glucose. A higher IAc also resulted in a larger decline in hunger if they consumed either glucose or sucralose. These data support the role of active inference in interoception and homeostasis, and suggest that the ability to attend to interoceptive signals may be critical to the maintenance of physical and emotional health.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Hyun-Ae Seo ◽  
In-Kyu Lee

Metabolic diseases, such as type 2 diabetes and obesity, are increasing globally, and much work has been performed to elucidate the regulatory mechanisms of these diseases. Nuclear factor E2-related factor 2 (Nrf2) is a basic leucine zipper transcription factor that serves as a primary cellular defense against the cytotoxic effects of oxidative stress. Recent studies have proposed a close relationship between oxidative stress and energy metabolism-associated disease. The Nrf2 pathway, as a master regulator of cellular defense against oxidative stress, has emerged as a critical target of energy metabolism; however, its effects are controversial. This review examines the current state of research on the role of Nrf2 on energy metabolism, specifically with respect to its participation in adipocyte differentiation, obesity, and insulin resistance, and discusses the possibility of using Nrf2 as a therapeutic target in the clinic.


2020 ◽  
Vol 14 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Ryusuke Suzuki ◽  
I Ketut Gunarta ◽  
Jambaldorj Boldbaatar ◽  
Purev Erdenebaatar ◽  
Ravdandorj Odongoo ◽  
...  

2020 ◽  
Vol 22 (1) ◽  
pp. 310
Author(s):  
Silvia Yumnam ◽  
Lalita Subedi ◽  
Sun Yeou Kim

Dicarbonyl compounds, including methylglyoxal (MGO) and glyoxal (GO), are mainly formed as byproducts of glucose metabolism. The main glyoxalase system consists of glyoxalase I and II (Glo1 and Glo2) and is the main enzyme involved in the detoxification of dicarbonyl stress, which occurs as an accumulation of MGO or GO due to decreased activity or expression of Glo1. Dicarbonyl stress is a major cause of cellular and tissue dysfunction that causes various health issues, including diabetes, aging, and cancer. The skin is the largest organ in the body. In this review, we discuss the role of the glyoxalase system in the progression of skin aging, and more importantly, skin malignancies. We also discuss the future prospects of the glyoxalase system in other skin abnormalities such as psoriasis and vitiligo, including hyperpigmentation. Finally, in the present review, we suggest the role of glyoxalase in the progression of skin aging and glyoxalase system as a potential target for anticancer drug development for skin cancer.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qi Zhang ◽  
Junli Wang ◽  
Dipesh Kumar Yadav ◽  
Xueli Bai ◽  
Tingbo Liang

Macrophages exist in most tissues of the body, where they perform various functions at the same time equilibrating with other cells to maintain immune responses in numerous diseases including cancer. Recently, emerging investigations revealed that metabolism profiles control macrophage phenotypes and functions, and in turn, polarization can trigger metabolic shifts in macrophages. Those findings implicate a special role of metabolism in tumor-associated macrophages (TAMs) because of the sophisticated microenvironment in cancer. Glucose is the major energy source of cells, especially for TAMs. However, the complicated association between TAMs and their glucose metabolism is still unclearly illustrated. Here, we review the recent advances in macrophage and glucose metabolism within the tumor microenvironment, and the significant transformations that occur in TAMs during the tumor progression. Additionally, we have also outlined the potential implications for macrophage-based therapies in cancer targeting TAMs.


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