Lipotoxicity dysregulates the immunoproteasome in podocytes and kidneys in type 2 diabetes

2021 ◽  
Vol 320 (4) ◽  
pp. F548-F558
Author(s):  
Hyun Soon Lee ◽  
Ji Yeon Suh ◽  
Byeong-Choel Kang ◽  
Eugene Lee
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Fish Oil ◽  
Olive Oil ◽  
Renal Cortex ◽  
Diabetic Mice ◽  
Podocyte Injury ◽  
Type 2 Diabetic

In podocytes, PA rapidly induced immunoproteasome expression but ultimately decreased it, while OA and EPA restored the decreased immunoproteasome levels. In the renal cortex of type 2 diabetic mice, immunoproteasome expression was significantly decreased, whereas feeding of OA-rich olive oil or EPA-rich fish oil diets protected them against the reduced immunoproteasome expression and progression of diabetic nephropathy. Thus, lipotoxicity-induced podocyte injury with impaired immunoproteasome expression may be related to the pathogenesis of diabetic nephropathy.

scholarly journals A study of prevalence of microalbuminuria in recently detected type 2 diabetes and its relation to hypertension, dyslipidaemia and obesity

2020 ◽  
Vol 11 (5) ◽  
pp. 38-43
Author(s):  
Shrikrishna V Acharya
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Screening Tool ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Group 2 ◽  
Type 2 Diabetic ◽  
Group 1 ◽  
New Onset

Background: Microalbuminuria is one of the earliest markers of diabetic nephropathy, and if not recognized and treated early it may lead to diabetic nephropathy resulting in chronic renal failure. Aims and Objective: The aim of the current study was to find out the prevalence of microalbuminuria among newly detected Type 2 diabetic patients and also compare prevalence of microalbuminuria in patients with or without hypertension, dyslipidaemia and obesity. Materials and Methods: In this retrospective study, we analysed 90 patients with new onset type 2 diabetes mellitus. We divided the patients into two groups, group 1 with comorbidities like hypertension, dyslipidaemia and obesity (50 patients) and group 2 without comorbidities (40 patients). We analysed urinary microalbumin level in all patients and compared the prevalence of microalbuminuria between group 1 and group 2. Results: In our cohort of 90 patients, urinary microalbuminuria was found in 30 patients (33.3%). When we divided these nephropathy patients to group1 and group 2, we observed that group 1 with comorbidities had higher percentage of nephropathy patients i.e 24 out of 50(48%). Group 2 with 40 patients had only 6 patients with microalbiminuria ie 6 out of 40(15%). Incidence of microalbiminuria was higher in patients with hypertension, dyslipidaemia and obesity. Conclusions: We conclude that incidence of microalbiminuria is much more common in newly diagnosed type 2 diabetes. We also conclude that hypertension, obesity and hypercholesterolemia are risk factors for nephropathy and urinary microalbuminuria appears to be much more sensitive than serum creatinine as screening tool to detect diabetic nephropathy.

scholarly journals CNDP1, NOS3, and MnSOD Polymorphisms as Risk Factors for Diabetic Nephropathy among Type 2 Diabetic Patients in Malaysia

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Mohd Jokha Yahya ◽  
Patimah Binti Ismail ◽  
Norshariza Binti Nordin ◽  
Abdah Binti Md Akim ◽  
Wan Shaariah Binti Md Yusuf ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Manganese Superoxide Dismutase ◽  
Multiplicative Model ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic ◽  
Mode Of Inheritance

Type 2 diabetes mellitus (T2DM) is associated with a high incidence of nephropathy. The aim of this study was to investigate the association of a genetic polymorphism of carnosinase (CNDP1-D18S880and -rs2346061), endothelial nitric oxide synthase (NOS3-rs1799983), and manganese superoxide dismutase (MnSOD-rs4880) genes with the development of diabetic nephropathy among Malaysian type 2 diabetic patients. A case-control association study was performed using 652 T2DM patients comprising 227 Malays (without nephropathy = 96 and nephropathy = 131), 203 Chinese (without nephropathy = 95 and nephropathy = 108), and 222 Indians (without nephropathy = 136 and nephropathy = 86). DNA sequencing was performed for theD18S880ofCNDP1, while the rest were tested using DNA Sequenom MassARRAY to identify the polymorphisms. DNA was extracted from the secondary blood samples taken from the T2DM patients. The alleles and genotypes were tested using four genetic models, and the best mode of inheritance was chosen based on the leastpvalue. Thers2346061ofCNDP1was significantly associated with diabetic nephropathy among the Indians only with OR = 1.94 and 95% CI = (1.76–3.20) and fitted best the multiplicative model, whileD18S880was associated among all the three major races with the Malays having the strongest association with OR = 2.46 and 95% CI = (1.48–4.10), Chinese with OR = 2.26 and 95% CI = (1.34–3.83), and Indians with OR = 1.77 and 95% CI = (1.18–2.65) in the genotypic multiplicative model. The best mode of inheritance for bothMnSODandNOS3was the additive model. ForMnSOD-rs4880, the Chinese had OR = 2.8 and 95% CI = (0.53–14.94), Indians had OR = 2.4 and 95% CI = (0.69–2.84), and Malays had OR = 2.16 and 95% CI = (0.54–8.65), while forNOS3-rs1799983, the Indians had the highest risk with OR = 3.16 and 95% CI = (0.52–17.56), followed by the Chinese with OR = 3.55 and 95% CI = (0.36–35.03) and the Malays with OR = 2.89 and 95% CI = (0.29–28.32). The four oxidative stress-related polymorphisms have significant effects on the development of nephropathy in type 2 diabetes patients. The genes may, therefore, be considered as risk factors for Malaysian subjects who are predisposed to T2DM nephropathy.

scholarly journals MiR-27b augments bone marrow progenitor cell survival via suppressing the mitochondrial apoptotic pathway in Type 2 diabetes

2017 ◽  
Vol 313 (4) ◽  
pp. E391-E401 ◽  
Author(s):  
Hainan Li ◽  
Jenny Liu ◽  
Yihan Wang ◽  
Zhiyao Fu ◽  
Maik Hüttemann ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
Cell Therapy ◽  
Progenitor Cell ◽  
Diabetic Mice ◽  
Tissue Repair And Regeneration ◽  
Autologous Cell ◽  
Autologous Cell Therapy ◽  
Type 2 Diabetic

Bone marrow-derived progenitor cells (BMPCs) are potential candidates for autologous cell therapy in tissue repair and regeneration because of their high angiogenic potential. However, increased progenitor cell apoptosis in diabetes directly limits their success in the clinic. MicroRNAs are endogenous noncoding RNAs that regulate gene expression at the posttranscriptional level, but their roles in BMPC-mediated angiogenesis are incompletely understood. In the present study, we tested the hypothesis that the proangiogenic miR-27b inhibits BMPC apoptosis in Type 2 diabetes. Bone marrow-derived EPCs from adult male Type 2 diabetic db/db mice and their normal littermates db/+ mice were used. MiR-27b expression (real-time PCR) in EPCs was decreased after 24 h of exposure to methylglyoxal (MGO) or oxidized low-density lipoprotein but not high glucose, advanced glycation end products, the reactive oxygen species generator LY83583, or H2O2. The increase in BMPC apoptosis in the diabetic mice was rescued following transfection with a miR-27b mimic, and the increased apoptosis induced by MGO was also rescued by the miR-27b mimic. p53 protein expression and the Bax/Bcl-2 ratio in EPCs (Western blot analyses) were significantly higher in db/db mice, both of which were suppressed by miR-27b. Furthermore, mitochondrial respiration, as measured by oxygen consumption rate, was enhanced by miR-27b in diabetic BMPCs, with concomitant decrease of mitochondrial Bax/Bcl-2 ratio. The 3′ UTR binding assays revealed that both Bax, and its activator RUNX1, were direct targets of miR-27b, suggesting that miR-27b inhibits Bax expression in both direct and indirect manners. miR-27b prevents EPC apoptosis in Type 2 diabetic mice, at least in part, by suppressing p53 and the Bax/Bcl-2 ratio. These findings may provide a mechanistic basis for rescuing BMPC dysfunction in diabetes for successful autologous cell therapy.

scholarly journals Decreased glycolytic and tricarboxylic acid cycle intermediates coincide with peripheral nervous system oxidative stress in a murine model of type 2 diabetes

2012 ◽  
Vol 216 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Lucy M Hinder ◽  
Anuradha Vivekanandan-Giri ◽  
Lisa L McLean ◽  
Subramaniam Pennathur ◽  
Eva L Feldman
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Sural Nerve ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Diabetic Mice ◽  
Type 2 Diabetic

Diabetic neuropathy (DN) is the most common complication of diabetes and is characterized by distal-to-proximal loss of peripheral nerve axons. The idea of tissue-specific pathological alterations in energy metabolism in diabetic complications-prone tissues is emerging. Altered nerve metabolism in type 1 diabetes models is observed; however, therapeutic strategies based on these models offer limited efficacy to type 2 diabetic patients with DN. Therefore, understanding how peripheral nerves metabolically adapt to the unique type 2 diabetic environment is critical to develop disease-modifying treatments. In the current study, we utilized targeted liquid chromatography–tandem mass spectrometry (LC/MS/MS) to characterize the glycolytic and tricarboxylic acid (TCA) cycle metabolomes in sural nerve, sciatic nerve, and dorsal root ganglia (DRG) from male type 2 diabetic mice (BKS.Cg-m+/+Leprdb;db/db) and controls (db/+). We report depletion of glycolytic intermediates in diabetic sural nerve and sciatic nerve (glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate (sural nerve only), 3-phosphoglycerate, 2-phosphoglycerate, phosphoenolpyruvate, and lactate), with no significant changes in DRG. Citrate and isocitrate TCA cycle intermediates were decreased in sural nerve, sciatic nerve, and DRG from diabetic mice. Utilizing LC/electrospray ionization/MS/MS and HPLC methods, we also observed increased protein and lipid oxidation (nitrotyrosine; hydroxyoctadecadienoic acids) indb/dbtissue, with a proximal-to-distal increase in oxidative stress, with associated decreased aconitase enzyme activity. We propose a preliminary model, whereby the greater change in metabolomic profile, increase in oxidative stress, and decrease in TCA cycle enzyme activity may cause distal peripheral nerves to rely on truncated TCA cycle metabolism in the type 2 diabetes environment.

scholarly journals Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Junghyun Kim ◽  
Eunjin Shon ◽  
Chan-Sik Kim ◽  
Jin Sook Kim
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Glycated Haemoglobin ◽  
Protective Effects ◽  
Podocyte Injury ◽  
Podocyte Loss ◽  
Renal Changes ◽  
Hypoglycemic Drug ◽  
Antioxidant Effects

Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT) rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day) was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c), and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG) levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.

scholarly journals The Efficacy of Red Ginseng in Type 1 and Type 2 Diabetes in Animals

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Bin Na Hong ◽  
Min Gun Ji ◽  
Tong Ho Kang
Keyword(s):  
Type 2 Diabetes ◽  
Signal Intensity ◽  
Diabetic Mice ◽  
Red Ginseng ◽  
Korean Red Ginseng ◽  
Diabetes In Animals ◽  
Brainstem Response ◽  
Type 2 Diabetic

Diabetes mellitus (DM) is one of the most modern chronic metabolic diseases in the world. Moreover, DM is one of the major causes of modern neurological diseases. In the present study, the therapeutic actions of Korean red ginseng were evaluated in type 1 and type 2 diabetic mouse models using auditory electrophysiological measurement. The comprehensive results from auditory brainstem response (ABR), auditory middle latency response (AMLR), and transient evoked otoacoustic emission (TEOAE) demonstrate auditory functional damage caused by type 1 or 2 DM. Korean red ginseng improved the hearing threshold shift, delayed latencies and signal intensity decrease in type 2 diabetic mice. Type 1 diabetic mice showed a partial improvement in decreasing amplitude and signal intensity, not significantly. We suggest that the Korean red ginseng has a more potent efficacy in hearing loss in insulin resistance type 2 diabetes than in type 1 diabetes.

scholarly journals Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model

2015 ◽  
Vol 309 (1) ◽  
pp. E45-E54 ◽  
Author(s):  
Minglong Shao ◽  
Lechu Yu ◽  
Fangfang Zhang ◽  
Xuemian Lu ◽  
Xiaokun Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Combination Treatment ◽  
Combined Treatment ◽  
Protective Effects ◽  
Diabetic Mice ◽  
Renal Protection ◽  
Glucose Levels

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways.

scholarly journals ID: 1080 Adipose-derived stem cells alleviate glucose tolerance in type 2 diabetic mouse

2017 ◽  
Vol 4 (S) ◽  
pp. 166
Author(s):  
Anh Nguyen Tu Bui ◽  
Cong Le Thanh Nguyen ◽  
Anh Thi Minh Nguyen ◽  
Nhat Chau Truong ◽  
Ngoc Kim Phan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Stem Cells ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Adipose Derived Stem Cells ◽  
Diabetic Mice ◽  
Human Ascs ◽  
Type 2 Diabetic

Background: Type 2 diabetes (T2D) is the most common form of diabetes and accounts for 90-95% of all existing diabetic cases. The main etiologies of T2D include insulin resistance in target tissues, insufficient secretion of insulin and subsequent decline of pancreatic β-cell function. Recently, many studies have suggested that adipose – derived stem cells (ASCs) were potential to alleviate insulin resistance and hyperglycemia and promote the islets repair. In this study, ASCs were hypothesized that they could have ameliorative effects on type 2 diabetic mice.  Methods: Type 2 diabetic mice were induced by a combination of high-fat diet and injection of STZ 100 mg/kg and NA 120 mg/kg. Thereafter, two doses of 106 human ASCs were transplanted 2 week interval into each mouse via the tail vein. The mice were monitored health condition, rate of mortaity, body weight, consumption of food and water, blood glucose level, serum insulin level and histological structure of pancreatic islets.  Results: Our results indicated that the ASC-treated mice expressed improved condition in comparision with non-treated diabetic mice. The consumption of food and water as well as the blood glucose level decreased. Simultaneously, ASC transplantation improved the impaired glucose tolerance and insulin tolerance in T2D mice. Besides, the total cholesterol have significantly decreased.  Conclusion: it is suggested that human ASCs infusion is safe and effective for type 2 diabetes mellitus in mice regarding the improved glucose metabolism and insulin resistance.

scholarly journals 102 Jurnal Kesehatan Andalas. 2015; 4(1) Pola Komplikasi Kronis Penderita Diabetes Melitus Tipe 2 Rawat Inap di Bagian Penyakit Dalam RS. Dr. M. Djamil Padang Januari 2011 - Desember 2012

2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Dwi Amelisa Edwina ◽  
Asman Manaf ◽  
Efrida Efrida
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Medical Record ◽  
Macrovascular Complications ◽  
Chronic Complications ◽  
Microvascular And Macrovascular Complications ◽  
Type 2 Diabetic ◽  
Diabetes Melitus

AbstrakDiabetes Melitus (DM) merupakan suatu kelompok penyakit metabolik dengan karakteristik hiperglikemia. DM tipe 2 adalah yang paling sering ditemukan. Komplikasi kronis DM tipe 2 yaitu mikrovaskular dan makrovaskular yang dapat menurunkan kualitas hidup penderita. Tujuan penelitian ini adalah untuk memperoleh gambaran tentang insidensi penderita DM tipe 2 dengan komplikasi kronis. Penelitian deskriptif ini dilakukan dengan mengambil data pada rekam medik penderita DM tipe 2 dengan komplikasi kronis yang dirawat inap di bagian Penyakit Dalam RS.Dr. M. Djamil, Padang Januari 2011-Desember 2012. Penelitian dilakukan dari Februari 2013-April 2013 di bagian rekam medik RS. Dr. M. Djamil Padang. Data didapatkan sebanyak 261 pasien, dari jumlah tersebut didapatkan 197 pasien memiliki komplikasi kronis DM tipe 2. Data dikategorikan berdasarkan jenis komplikasi makrovaskular dan mikrovaskular. Hasil penelitian menunjukkan bahwa penderita dengan komplikasi kronis makrovaskular (66,5%) dan mikrovaskular (81,7%). Terdapat perubahan insidensi dalam dua tahun yaitu dari tahun 2011 dengan 2012. Komplikasi kronis yang paling sering terjadi adalah nefropati diabetik (42,6%) pada perempuan <60 tahun.Kata kunci: diabetes melitus, komplikasi mikrovaskular, komplikasi makrovaskularAbstractDiabetes mellitus is a group of metabolic diseases with characterized by hyperglycemia. Type 2 diabetes is the most common disease in the world. Chronic complications of type 2 diabetes are microvascular and macrovascular complications that can reduce the quality of life of patients. The objective of this study was to obtain a picture of the incidence of type 2 diabetic chronic complications. This descriptive study was conducted by taking medical record data of hospitalized type 2 diabetic patients with chronic complications inInternal Medicine Department Dr. M. Djamil hospital, Padang on January 2011-December 2012. The study was conducted from February 2013-April 2013 at the hospital medical record Dr. M. Djamil, Padang. This study was conducted on 261 patients, from that number 197 patients have chronic complications of type 2 diabetes mellitus. Data were categorized by type of macrovascular and microvascular complications.The results showed that patients with chronic complications of macrovascular (66,5%) and microvascular (81,7%). There is a change in incidence from 2011 to 2012. The most common of chronic complications is diabetic nephropathy (42.6%). Chronic microvascular and macrovascular complications are different incidence in two years, the most common is diabetic nephropathy which often occurs in women <60 years.Keyword: diabetes mellitus, microvascular complication, macrovacular complication.

scholarly journals Enhanced p22phox expression impairs vascular function through p38 and ERK1/2 MAP kinase-dependent mechanisms in type 2 diabetic mice

2014 ◽  
Vol 306 (7) ◽  
pp. H972-H980 ◽  
Author(s):  
Modar Kassan ◽  
Soo-Kyoung Choi ◽  
Maria Galán ◽  
Young-Ho Lee ◽  
Mohamed Trebak ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Nadph Oxidase ◽  
Vascular Function ◽  
Small Interfering Rna ◽  
Diabetic Mice ◽  
Mitogen Activated Protein ◽  
Ros Scavenger ◽  
Interfering Rna ◽  
Type 2 Diabetic

Type 2 diabetes is associated with vascular complication. We hypothesized that increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p22 phox expression impairs vascular endothelium-dependent relaxation (EDR) in type 2 diabetes. Type 2 diabetic ( db − /db −) and control ( db − /db +) mice were treated with reactive oxygen species (ROS) scavenger, polyethylene glycol superoxide dismutase (1,000 U/kg daily ip), or small interfering RNA p22 phox (p22 phox-lentivirus-small interfering RNA, 100 μg iv, 2 times/wk) for 1 mo. EDR was impaired in microvascular bed (coronary arteriole and femoral and mesenteric resistance arteries) from diabetic mice compared with control. Interestingly, ROS scavenger and p22 phox downregulation did not affect blood glucose level or body weight but significantly improved EDR. Mitogen-activated protein kinases (ERK1/2 and p38) phosphorylation and NADPH oxidase activity were increased in arteries from diabetic mice and were reduced after ROS scavenger or p22 phox downregulation in db − /db − mice. The present study showed that enhanced p22 phox expression causes vascular dysfunction through ERK1/2 and p38-mitogen-activated protein kinase-dependent mechanisms in male type 2 diabetic mice. Therefore, p22 phox could be an important target to improve vascular function in diabetes.

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