scholarly journals Loss of PDK1 Induces Meiotic Defects in Oocytes From Diabetic Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Juan Ge ◽  
Na Zhang ◽  
Shoubin Tang ◽  
Feifei Hu ◽  
Xiaojing Hou ◽  
...  
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Maternal Diabetes ◽  
Diabetic Mouse ◽  
Oocyte Quality ◽  
Pyruvate Dehydrogenase Kinase ◽  
Metabolic Dysfunction ◽  
Diabetic Mice ◽  
Α Subunit ◽  
Oocyte Competence ◽  
Beneficial Effects

Maternal diabetes has been shown to impair oocyte quality; however, the underlying mechanisms remain unclear. Here, using a streptozotocin (STZ)-induced diabetic mouse model, we first detected and reduced expression of pyruvate dehydrogenase kinase 1 (PDK1) in diabetic oocytes, accompanying with the lowered phosphorylation of serine residue 232 on α subunit of the pyruvate dehydrogenase (PDH) complex (Ser232-PDHE1α). Importantly, forced expression of PDK1 not only elevated the phosphorylation level of Ser232-PDHE1α, but also partly prevented the spindle disorganization and chromosome misalignment in oocytes from diabetic mice, with no beneficial effects on metabolic dysfunction. Moreover, a phospho-mimetic S232D-PDHE1α mutant is also capable of ameliorating the maternal diabetes-associated meiotic defects. In sum, our data indicate that PDK1-controlled Ser232-PDHE1α phosphorylation pathway mediates the effects of diabetic environment on oocyte competence.

scholarly journals Crocin Improves Insulin Sensitivity and Ameliorates Adiposity by Regulating AMPK-CDK5-PPARγ Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Kai Fang ◽  
Ming Gu
Keyword(s):  
Protein Level ◽  
Biological Activities ◽  
Protective Effects ◽  
Metabolic Dysfunction ◽  
Ampk Activation ◽  
Diabetic Mice ◽  
Wild Type ◽  
Ampk Signaling ◽  
Beneficial Effects

Crocin is a carotenoid compound which possesses multiple biological activities. Our and other laboratory’s previous findings show that crocin alleviates obesity and type 2 diabetes-related complications. We have found that crocin activates AMP-activated protein kinase (AMPK) signaling and inhibition of AMPK suppresses crocin-induced protective effects. However, the causal role of AMPK activation in the biological role of crocin is still not verified. In the present study, we showed that crocin markedly inhibits the changes of glucose metabolic parameters and serum lipid profiles in wild type diabetic mice. In AMPKα KO diabetic mice, those protective effects of crocin against glucose and lipid metabolic dysfunction were abolished. These results demonstrated AMPK activation was responsible for the beneficial effects of crocin on metabolic dysfunction. Moreover, we have shown that the antiobese effect of crocin has been abolished by the deficiency of AMPKα. We also showed that crocin induced a significant decrease of CDK5 protein level in wild type diabetic mice, while this effect was abolished in AMPKα KO diabetic mice. The regulation of downstream targets of CDK5/PPARγ by crocin was abolished by the deficiency of AMPK. In conclusion, our study verified that activation of AMPK is involved in crocin-induced protective effects against glucose and lipid metabolic dysfunction. Activation of AMPK downregulates the protein level of CDK5, followed by the decrease of PPARγ phosphorylation, leading to the inhibition of adipose formation and metabolic dysfunction. Our study provides new insights into the mechanism of protective effects of crocin and interaction of AMPK and CDK5/PPARγ signaling.

scholarly journals Quetiapine Attenuates the Neuroinflammation and Executive Function Deficit in Streptozotocin-Induced Diabetic Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Kexin Wang ◽  
Feng Song ◽  
Hongxing Wang ◽  
Jun-hui Wang ◽  
Yu Sun
Keyword(s):  
Cognitive Deficit ◽  
Neuroprotective Effect ◽  
Underlying Mechanism ◽  
Diabetic Mouse ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Protein Loss ◽  
Monocyte Chemoattractant Protein 1 ◽  
Beneficial Effects ◽  
Increased Risk

Diabetic patients are at increased risk for developing memory and cognitive deficit. Prior studies indicate that neuroinflammation might be one important underlying mechanism responsible for this deficit. Quetiapine (QTP) reportedly exerts a significant neuroprotective effect in animal and human studies. Here, we investigated whether QTP could prevent memory deterioration and cognitive impairment in a streptozotocin- (STZ-) induced diabetic mouse model. In this study, we found that STZ significantly compromised the behavioral performance of mice in a puzzle box test, but administering QTP effectively attenuated this behavioral deficit. Moreover, our results showed that QTP could significantly inhibit the activation of astrocytes and microglia in these diabetic mice and reduce the generation and release of two cytokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). Meanwhile, QTP also prevented the protein loss of the synaptic protein synaptophysin (SYP) and myelin basic protein (MBP). Here, our results indicate that QTP could inhibit neuroinflammatory response from glial cells and block the injury of released cytokines to neurons and oligodendrocytes in diabetic mice (DM). These beneficial effects could protect diabetic mice from the memory and cognitive deficit. QTP may be a potential treatment compound to handle the memory and cognitive dysfunction in diabetic patients.

scholarly journals Maternal Diabetes Causes Mitochondrial Dysfunction and Meiotic Defects in Murine Oocytes

2009 ◽  
Vol 94 (9) ◽  
pp. 3618-3618
Author(s):  
Qiang Wang ◽  
Ann M. Ratchford ◽  
Maggie M.-Y. Chi ◽  
Erica Schoeller ◽  
Antonina Frolova ◽  
...  
Keyword(s):  
Tricarboxylic Acid Cycle ◽  
Maternal Diabetes ◽  
Meiotic Spindle ◽  
Metabolic Dysfunction ◽  
Diabetic Mice ◽  
Abnormal Distribution ◽  
Mitochondrial Dna Copy Number ◽  
Transmission Electron ◽  
The One ◽  
Zygote Stage

The adverse effects of maternal diabetes on embryo development and pregnancy outcomes have recently been shown to occur as early as the one-cell zygote stage. The hypothesis of this study was that maternally inherited mitochondria in oocytes from diabetic mice are abnormal and thus responsible in part for this latency of developmental compromise. In ovulated oocytes from diabetic mice, transmission electron microscopy revealed an alteration in mitochondrial ultrastructure, and the quantitative analysis of mitochondrial DNA copy number demonstrated an increase. The levels of ATP and tricarboxylic acid cycle metabolites in diabetic oocytes were markedly reduced compared with controls, suggesting a mitochondrial metabolic dysfunction. Abnormal distribution of mitochondria within maturing oocytes also was seen in diabetic mice. Furthermore, oocytes from diabetic mice displayed a higher frequency of spindle defects and chromosome misalignment in meiosis, resulting in increased aneuploidy rates in ovulated oocytes. Collectively, our results suggest that maternal diabetes results in oocyte defects that are transmitted to the fetus by two routes: first, meiotic spindle and chromatin defects result in nondisjunction leading to embryonic aneuploidy; second, structural and functional abnormalities of oocyte mitochondria, through maternal transmission, provide the embryo with a dysfunctional complement of mitochondria that may be propagated during embryogenesis.

scholarly journals Qiliqiangxin Rescues Mouse Cardiac Function by Regulating AGTR1/TRPV1-Mediated Autophagy in STZ-Induced Diabetes Mellitus

2018 ◽  
Vol 47 (4) ◽  
pp. 1365-1376 ◽  
Author(s):  
Jing Tong ◽  
Yan Lai ◽  
Yi-An Yao ◽  
Xue-Jun Wang ◽  
Yu-Shuang Shi ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Function ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Diabetic Mouse ◽  
Transient Receptor Potential Vanilloid ◽  
Ang Ii ◽  
Diabetic Mice ◽  
Angiotensin Ii Receptor ◽  
Beneficial Effects

Background/Aims: To explore the potential role of qiliqiangxin (QLQX) A traditional Chinese medicine and the involvement of angiotensin II receptor type 1 (AGTR1) and transient receptor potential vanilloid 1 (TRPV1) in diabetic mouse cardiac function. Methods: Intragastric QLQX was administered for 5 weeks after streptozotocin (STZ) treatment. Additionally, Intraperitoneal injections of angiotensin II (Ang II) or intragastric losartan (Los) were administered to assess the activities of AGTR1 and TRPV1. Two-dimensional echocardiography and tissue histopathology were used to assess cardiac function Western blot was used to detect the autophagic biomarkers Such as light chain 3 P62 and lysosomal-associated membrane protein 2 And transmission electron microscopy was used to count the number of autophagosomes. Results: Decreased expression of TRPV1 and autophagic hallmarks and reduced numbers of autophagolysosomes as well as increased expression of angiotensin converting enzyme 1 and AGTR1 were observed in diabetic hearts. Blocking AGTR1 with Los mimicked the QLQX-mediated improvements in cardiac function Alleviated myocardial fibrosis and enabled autophagy Whereas Ang II abolished the beneficial effects of QLQX in wild type diabetic mice but not in TRPV1-/- diabetic mice. Conclusions: QLQX may improve diabetic cardiac function by regulating AGTR1/ TRPV1-mediated autophagy in STZ-induced diabetic mice.

scholarly journals The Effect of Various Fatty Acids on Activity of G6pase-A and Pdk4 in Hepg2 CellA

2019 ◽  
pp. 1-6
Author(s):  
Lisa Maness ◽  
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Kinase ◽  
Increase Insulin Sensitivity ◽  
Beneficial Effects ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
Arachidonic Acids

Aims: The current study aimed to determine the effects of various fatty acids on the expression of glucose-6-phosphatase-α (G6Pase-α) and pyruvate dehydrogenase kinase 4 (PDK4). Methods: HepG2 cells were seeded in a 96-well plate with Dulbecco’s Modified Eagle Media, high glucose and bovine serum albumin with 25 µmoll of each fatty acid individually (butyric, politic, stearic, oleic, linoleic, linolenic, and arachidonic acids) for 24 hours at 37°C with and without 10 minute incubation of 100 nmol insulin. qPCR was performed using G6Pase-α and PDK4 primers; fold-changes in gene activity were determined. Results: Butyric (-2.0) and linoleic (-65.8) acids caused down regulations of G6Pase-α in the presence of insulin while linoleic (-96.6) acid caused a down regulation of PDK4 in the presence of insulin; all caused upregulations of both these genes in the absence of insulin. Conclusions: This study suggests that linolenic acid, which is present in soybeans, walnuts, and kiwi seeds, is beneficial to processing glucose and could increase insulin sensitivity through molecular influence in patients with metabolic syndrome or serve as prevention. Other fatty acids tested, with exception of butyric acid, did not show beneficial effects in the direction of decreasing glucose

scholarly journals Maternal Diabetes Causes Mitochondrial Dysfunction and Meiotic Defects in Murine Oocytes

2009 ◽  
Vol 23 (10) ◽  
pp. 1603-1612 ◽  
Author(s):  
Qiang Wang ◽  
Ann M. Ratchford ◽  
Maggie M.-Y. Chi ◽  
Erica Schoeller ◽  
Antonina Frolova ◽  
...  
Keyword(s):  
Tricarboxylic Acid Cycle ◽  
Maternal Diabetes ◽  
Meiotic Spindle ◽  
Metabolic Dysfunction ◽  
Diabetic Mice ◽  
Abnormal Distribution ◽  
Mitochondrial Dna Copy Number ◽  
Transmission Electron ◽  
The One ◽  
Zygote Stage

Abstract The adverse effects of maternal diabetes on embryo development and pregnancy outcomes have recently been shown to occur as early as the one-cell zygote stage. The hypothesis of this study was that maternally inherited mitochondria in oocytes from diabetic mice are abnormal and thus responsible in part for this latency of developmental compromise. In ovulated oocytes from diabetic mice, transmission electron microscopy revealed an alteration in mitochondrial ultrastructure, and the quantitative analysis of mitochondrial DNA copy number demonstrated an increase. The levels of ATP and tricarboxylic acid cycle metabolites in diabetic oocytes were markedly reduced compared with controls, suggesting a mitochondrial metabolic dysfunction. Abnormal distribution of mitochondria within maturing oocytes also was seen in diabetic mice. Furthermore, oocytes from diabetic mice displayed a higher frequency of spindle defects and chromosome misalignment in meiosis, resulting in increased aneuploidy rates in ovulated oocytes. Collectively, our results suggest that maternal diabetes results in oocyte defects that are transmitted to the fetus by two routes: first, meiotic spindle and chromatin defects result in nondisjunction leading to embryonic aneuploidy; second, structural and functional abnormalities of oocyte mitochondria, through maternal transmission, provide the embryo with a dysfunctional complement of mitochondria that may be propagated during embryogenesis.

Pyruvate dehydrogenase activity in cardiac mitochondria from genetically diabetic mice

Diabetes ◽  
1985 ◽  
Vol 34 (11) ◽  
pp. 1075-1081 ◽  
Author(s):  
T. H. Kuo ◽  
F. Giacomelli ◽  
J. Wiener ◽  
K. Lapanowski-Netzel
Keyword(s):  
Dehydrogenase Activity ◽  
Pyruvate Dehydrogenase ◽  
Diabetic Mice ◽  
Cardiac Mitochondria ◽  
Genetically Diabetic Mice

Therapeutic Approaches to Alzheimer’s Type of Dementia: A Focus on FGF21 Mediated Neuroprotection

2019 ◽  
Vol 25 (23) ◽  
pp. 2555-2568 ◽  
Author(s):  
Rajeev Taliyan ◽  
Sarathlal K. Chandran ◽  
Violina Kakoty
Keyword(s):  
Diabetes Mellitus ◽  
Protein Trafficking ◽  
Metabolic Stress ◽  
Insulin Receptors ◽  
Metabolic Dysfunction ◽  
Beneficial Effects ◽  
Glucose And Lipid Metabolism ◽  
Endocrine Hormone ◽  
Metabolic Conditions ◽  
The Brain

Neurodegenerative disorders are the most devastating disorder of the nervous system. The pathological basis of neurodegeneration is linked with dysfunctional protein trafficking, mitochondrial stress, environmental factors and aging. With the identification of insulin and insulin receptors in some parts of the brain, it has become evident that certain metabolic conditions associated with insulin dysfunction like Type 2 diabetes mellitus (T2DM), dyslipidemia, obesity etc., are also known to contribute to neurodegeneration mainly Alzheimer’s Disease (AD). Recently, a member of the fibroblast growth factor (FGF) superfamily, FGF21 has proved tremendous efficacy in diseases like diabetes mellitus, obesity and insulin resistance (IR). Increased levels of FGF21 have been reported to exert multiple beneficial effects in metabolic syndrome. FGF21 receptors are present in certain areas of the brain involved in learning and memory. However, despite extensive research, its function as a neuroprotectant in AD remains elusive. FGF21 is a circulating endocrine hormone which is mainly secreted by the liver primarily in fasting conditions. FGF21 exerts its effects after binding to FGFR1 and co-receptor, β-klotho (KLB). It is involved in regulating energy via glucose and lipid metabolism. It is believed that aberrant FGF21 signalling might account for various anomalies like neurodegeneration, cancer, metabolic dysfunction etc. Hence, this review will majorly focus on FGF21 role as a neuroprotectant and potential metabolic regulator. Moreover, we will also review its potential as an emerging candidate for combating metabolic stress induced neurodegenerative abnormalities.

scholarly journals Hypoxic Exposure Increases Energy Expenditure by Increasing Carbohydrate Oxidation in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yeram Park ◽  
Deunsol Hwang ◽  
Hun-Young Park ◽  
Jisu Kim ◽  
Kiwon Lim
Keyword(s):  
Glucose Metabolism ◽  
Energy Expenditure ◽  
Pyruvate Dehydrogenase ◽  
Hypoxic Condition ◽  
Open Circuit ◽  
Pyruvate Dehydrogenase Kinase ◽  
Hypoxic Exposure ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Aims. Hypoxic exposure improves glucose metabolism. We investigated to validate the hypothesis that carbohydrate (CHO) oxidation could increase in mice exposed to severe hypoxic conditions. Methods. Seven-week-old male ICR mice (n=16) were randomly divided into two groups: the control group (CON) was kept in normoxic condition (fraction of inspired O2=21%) and the hypoxia group (HYP) was exposed to hypoxic condition (fraction of inspired O2=12%, ≈altitude of 4,300 m). The CON group was pair-fed with the HYP group. After 3 weeks of hypoxic exposure, we measured respiratory metabolism (energy expenditure and substrate utilization) at normoxic conditions for 24 hours using an open-circuit calorimetry system. In addition, we investigated changes in carbohydrate mechanism-related protein expression, including hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), and regulator of the genes involved in energy metabolism (peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC1α) in soleus muscle. Results. Energy expenditure (EE) and CHO oxidation over 24 hours were higher in the HYP group by approximately 15% and 34% (p<0.001), respectively. Fat oxidation was approximately 29% lower in the HYP group than the CON group (p<0.01). Body weight gains were significantly lower in the HYP group than in the CON group (CON vs. HYP; 1.9±0.9 vs. −0.3±0.9; p<0.001). Hypoxic exposure for 3 weeks significantly reduced body fat by approximately 42% (p<0.001). PDH and PGC1α protein levels were significantly higher in the HYP group (p<0.05). Additionally, HK2 was approximately 21% higher in the HYP group. Conclusions. Hypoxic exposure might significantly enhance CHO oxidation by increasing the expression of PDH and HK2. This investigation can be useful for patients with impaired glucose metabolism, such as those with type 2 diabetes.

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