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Impaired glucose regulation

Susan J Burke, Heidi M Batdorf, David H Burk, Thomas M Martin, Tamra Mendoza, Krisztian Stadler, Wateen Alami, Michael D Karlstad, Matthew J Robson, Randy D Blakely, Randall L Mynatt, J Jason Collier
OBJECTIVE: Pancreatic tissue, and islets in particular, are enriched in expression of the interleukin-1 receptor type I (IL-1R). Because of this enrichment, islet β-cells are exquisitely sensitive to the IL-1R ligands IL-1α and IL-1β, suggesting that signaling through this pathway regulates health and function of islet β-cells. METHODS: Herein, we report a targeted deletion of IL-1R in pancreatic tissue (IL-1RPdx1-/- ) in C57BL/6J mice and in db/db mice on the C57 genetic background...
June 6, 2018: Molecular Metabolism
Ryo Fujita, Kiyoshi Yoshioka, Daiki Seko, Takashi Suematsu, Satomi Mitsuhashi, Nanami Senoo, Shinji Miura, Ichizo Nishino, Yusuke Ono
Muscle mitochondria are crucial for systemic metabolic function, yet their regulation remains unclear. The zinc finger MYND domain-containing protein 17 (Zmynd17) was recently identified as a muscle-specific gene in mammals. Here, we investigated the role of Zmynd17 in mice. We found Zmynd17 predominantly expressed in skeletal muscle, especially in fast glycolytic muscle. Genetic Zmynd17 inactivation led to morphologic and functional abnormalities in muscle mitochondria, resulting in decreased respiratory function...
April 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ayyaraju Middepogu, Jie Hou, Xuan Gao, Daohui Lin
Titanium dioxide nanoparticles (n-TiO2 ) have been used in numerous applications, which results in their release into aquatic ecosystems and impact algal populations. A possible toxic mechanism of n-TiO2 on algae is via the disruption of the photosynthetic biochemical pathways, which yet remains to be demonstrated. In this study, Chlorella pyrenoidosa was exposed to different concentrations (0, 0.1, 1, 5, 10, and 20 mg/L) of a type of anatase n-TiO2 , and the physiological, biochemical, and molecular responses involved in photosynthesis were investigated...
June 14, 2018: Ecotoxicology and Environmental Safety
Mahmoud El-Daly, Vivek Krishna Pulakazhi Venu, Mahmoud Saifeddine, Koichiro Mihara, Sean Kang, Paul W M Fedak, Laurie A Alston, Simon A Hirota, Hong Ding, Chris R Triggle, Morley D Hollenberg
Hyperglycaemia is a major contributor to diabetic cardiovascular disease with hyperglycaemia-induced endothelial dysfunction recognized as the initiating cause. Coagulation pathway-regulated proteinase-activated receptors (PARs) that can regulate vascular tone in vivo cause eNOS-mediated endothelium-dependent vasodilation; but, the impact of hyperglycaemia on this vasodilatory action of PAR stimulation and the signalling pathways involved are unknown. We hypothesized that vascular sodium-glucose co-transporter 2 activity and hyperglycaemia-induced oxidative stress involving Src-kinase, EGF receptor-kinase, Rho-kinase and protein-kinase-C biochemical signalling pathways would compromise PAR2-mediated endothelium-dependent vasodilation...
June 13, 2018: Vascular Pharmacology
Ginevra Sacripanti, Nhat Minh Nguyen, Leonardo Lorenzini, Sabina Frascarelli, Alessandro Saba, Riccardo Zucchi, Sandra Ghelardoni
3,5-diiodo-l-thyronine (T2) is an endogenous derivative of thyroid hormone that has been suggested to regulate energy expenditure, resting metabolic rate and oxygen consumption with a mechanism that involves the activation of mitochondrial function. In this study, we focused on the cardiac effects of T2, which have been poorly investigated so far, by using both in vitro and ex vivo models. As a comparison, the response to T3 and T4 was also determined. Rat cardiomyoblasts (H9c2 cells) were used to determine T2, T3, and T4 uptake by high-performance liquid chromatography-tandem mass spectrometry...
2018: Frontiers in Endocrinology
Soh Yamamoto, Kenta Kuramoto, Nan Wang, Xiaolei Situ, Medha Priyadarshini, Weiran Zhang, Jose Cordoba-Chacon, Brian T Layden, Congcong He
Autophagy, a stress-induced lysosomal degradative pathway, has been assumed to exert similar metabolic effects in different organs. Here, we establish a model where autophagy plays different roles in insulin-producing β cells versus insulin-responsive cells, utilizing knockin (Becn1F121A ) mice manifesting constitutively active autophagy. With a high-fat-diet challenge, the autophagy-hyperactive mice unexpectedly show impaired glucose tolerance, but improved insulin sensitivity, compared to mice with normal autophagy...
June 12, 2018: Cell Reports
Hung-Wen Liu, Sue-Joan Chang
The clear mechanism of moderate exercise training (Ex) in attenuating muscle loss remains elusive in diabetes. We investigated the effects of moderate exercise training on diabetes-induced nuclear factor-κB (NF-κB) activation and mitochondrial dysfunction. Skeletal muscle size and atrophy signaling pathways were examined in type 2 diabetic db/db mice with or without moderate exercise training (5.2 m/min, 1 h/day, and 5 days/week for a total of 8 weeks). Exercise training decreased serum leptin, MCP-1, and resistin levels in db/db +Ex mice, but it did not reduce symptoms of insulin resistance including hyperglycemia, hyperinsulinemia, and impaired glucose tolerance...
2018: Frontiers in Physiology
Sabrina Corbetta, G Mantovani, A Spada
Parathyroid glands are the main regulator of body mineral metabolism through parathormone (PTH) actions on bone and kidney. Experimental evidence suggests that PTH may have non-classical target organs such as adipose tissue, arterial vascular wall, cardiac muscle cells, and adrenal cortex cells, where it may play a role in controlling body energy, blood pressure, and metabolism. Cardiometabolic features have been investigated in the wide spectrum of clinical parathyroid disorders, from hyperparathyroidism to pseudohypoparathyroidism and hypoparathyroidism...
2018: Frontiers of Hormone Research
Pierre-Alain Thiebaut, Eugénie Delile, David Coquerel, Jean-Michel Brunel, Sylvanie Renet, Fabienne Tamion, Vincent Richard
Protein tyrosine phosphatase 1B (PTP1B) impairs nitric oxide (NO) production and induces endothelial dysfunction in various diseases, including diabetes, septic shock and heart failure. In non-cardiovascular tissues, PTP1B modulates endoplasmic reticulum stress (ERS) however this role has never been assessed in endothelial cells. We evaluated the link between PTP1B, ERS and endothelial dysfunction in mice. Induction of ERS (Tunicamycin) in vivo in mice or ex vivo in mouse arteries led to severe arterial endothelial dysfunction (i...
June 9, 2018: Vascular Pharmacology
Takumi Ohdate, Fumihiko Omura, Haruyo Hatanaka, Yan Zhou, Masami Takagi, Tetsuya Goshima, Takeshi Akao, Eiichiro Ono
For maltose fermentation, budding yeast Saccharomyces cerevisiae operates a mechanism that involves transporters (MALT), maltases (MALS) and regulators (MALR) collectively known as MAL genes. However, functional relevance of MAL genes during sake brewing process remains largely elusive, since sake yeast is cultured under glucose-rich condition achieved by the co-culture partner Aspergillus spp.. Here we isolated an ethyl methane sulfonate (EMS)-mutagenized sake yeast strain exhibiting enhanced maltose fermentation compared to the parental strain...
2018: PloS One
Charles V Mobbs
During differentiation transient, inducers produce permanent changes in gene expression. A similar phenomenon, transcriptional hysteresis, produced by transient or prolonged exposure to glucose, leads to cumulative, persistent, and largely irreversible effects on glucose-regulated gene expression, and may drive key aspects of metabolic memory, obesity, diabetes, and aging, and explain the protective effects of dietary restriction during aging. The most relevant effects of glucose-induced transcriptional hysteresis are the persistent effects of elevated glucose on genes that control glucose metabolism itself...
2018: Frontiers in Endocrinology
Carmen Pheiffer, Stephanie Dias, Tarryn Willmer, Ryan Pace, Kjersti Aagaard, Johan Louw
OBJECTIVE: MicroRNAs (miRNAs) play a critical role in metabolic regulation. Recently, we identified novel miRNAs in the whole blood of South African women of mixed ethnic ancestry. The aim of this study was to investigate whether five of these novel miRNAs are expressed in serum and whether their expression is altered during metabolic dysregulation. METHODS: Expression levels of the five novel miRNAs (MYN08, MYNO22, MYN059, MYNO66 and MYNO95) were measured in the serum of women with Impaired Glucose Tolerance (IGT) and Normoglycemia (NGT) (n=24), and in the whole blood of vervet monkeys fed a high-fat or standard diet (n=16) using quantitative real-time PCR...
June 11, 2018: Experimental and Clinical Endocrinology & Diabetes
Elena Daveri, Eleonora Cremonini, Angela Mastaloudis, Shelly N Hester, Steven M Wood, Andrew L Waterhouse, Mauri Anderson, Cesar G Fraga, Patricia I Oteiza
Consumption of diets high in fat and/or fructose content promotes tissue inflammation, oxidative stress, and insulin resistance, activating signals (e.g. NF-κB/JNK) that downregulate the insulin cascade. Current evidence supports the concept that select flavonoids can mitigate obesity and type 2 diabetes (T2D). This work investigated if supplementation with the anthocyanidins (AC) cyanidin and delphinidin could attenuate the adverse consequences of consuming a high fat diet (HFD) in mice. Consumption of an AC-rich blend mitigated HFD-induced obesity, dyslipidemia and insulin resistance (impaired responses to insulin and glucose)...
May 30, 2018: Redox Biology
Min-Hui Li, Hao Hong, Sheng-Feng Lu, Jun-Meng Wang, Bing-Mei Zhu
OBJECTIVE: To observe the effect of electroacupuncture (EA) on insulin signaling pathway in liver tissues of central neuronal specific signal transduction and activator of transcription 5 conditional-knockout ( Stat 5 NKO) mice, so as to explore its mechanism underlying improvement of insulin resistance (IR).. METHODS: Twenty-four male Stat 5 NKO mice were randomly divided into model and EA groups ( n =12 mice/group), and 12 Stat 5 fl/fl mice were used as the normal control group...
May 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
Yupaporn Rattanavichit, Jariya Buniam, Juthamard Surapongchai, Vitoon Saengsirisuwan
We have recently reported that male rats given liquid fructose ingestion exhibit features of cardiometabolic abnormalities including non-obese insulin resistance with impaired insulin signaling transduction in skeletal muscle (Rattanavichit Y et al. Am J Physiol Regul Integr Comp Physiol 311: R1200-R1212, 2016). While exercise can attenuate obesity-related risks of cardiometabolic syndrome, the effectiveness and potential mechanism by which exercise modulates non-obese insulin resistance have not been fully studied...
June 7, 2018: Journal of Physiology and Biochemistry
Na Li, Zhao Yang, Qing Li, Zhen Yu, Xu Chen, Jia-Cheng Li, Bo Li, Shang-Lei Ning, Min Cui, Jin-Peng Sun, Xiao Yu
The somatostatin (SST)-secreting cells were mainly distributed in the pancreatic islets, brain, stomach and intestine in mammals and have many physiological functions. In particular, the SST-secreting δ cell is the third most common cell type in the islets of Langerhans. Recent studies have suggested that dysregulation of paracrine interaction between the pancreatic δ cells and β cells results in impaired glucose homeostasis and contributes to diabetes development. However, direct evidence of the functional importance of SST cells in glucose homeostasis control is still lacking...
June 7, 2018: Cell Death & Disease
Naoufal Akla, Claire Viallard, Natalija Popovic, Cindy Lora Gil, Przemyslaw Sapieha, Bruno Larrivée
OBJECTIVE: Diabetic macular edema is a major cause of visual impairment in diabetic retinopathy. It is caused by blood-retinal barrier breakdown that leads to vascular hyperpermeability. Current therapeutic approaches consist of retinal photocoagulation or targeting VEGF (vascular endothelial growth factor) to limit vascular leakage. However, long-term intravitreal use of anti-VEGFs is associated with potential safety issue, and the identification of alternative regulators of vascular permeability may provide safer therapeutic options...
June 7, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Fang Chen, Yingkun He, Pengwen Wang, Peng Wei, Huili Feng, Yingxue Rao, Jing Shi, Jinzhou Tian
Reduced glucose utilization and deficient energy metabolism that occur in the early stages of Alzheimer's disease correlate with impaired cognition, and this information is evidence that Alzheimer's disease is a metabolic disease that is associated with brain insulin/insulin-like growth factor resistance. This research aimed to investigate the effects of Banxia Xiexin decoction (BXD) on cognitive deficits in APPswe/PS1dE9 double transgenic mice and verify the hypothesis that BXD treatment improves cognitive function via improving insulin signalling, glucose metabolism and synaptic plasticity in the hippocampus of APPswe/PS1dE9 double transgenic mice...
January 2018: International Journal of Immunopathology and Pharmacology
Yuan Li, Quan Li, Chun-Shui Pan, Li Yan, Bai-He Hu, Yu-Ying Liu, Lei Yang, Ping Huang, Shao-Yang Zhao, Chuan-She Wang, Jing-Yu Fan, Xue-Mei Wang, Jing-Yan Han
Type 2 Diabetes mellitus (T2DM) is closely correlated with cognitive impairment and neurodegenerative disease. Bushen Huoxue (BSHX) is a compound Chinese medicine used clinically to treat diabetes-induced cognitive impairment. However, its underlying mechanisms remain unclear. In the present study, KKAy mice, a genetic model of type 2 diabetes with obesity and insulin resistant hyperglycemia, received a daily administration of BSHX for 12 weeks. Blood glucose was measured every 4 weeks. After 12 weeks, BSHX treatment significantly ameliorated the T2DM related insults, including the increased blood glucose, the impaired spatial memory, decreased cerebral blood flow (CBF), occurrence of albumin leakage, leukocyte adhesion and opening capillary rarefaction...
2018: Frontiers in Physiology
Rongya Tao, Caixia Wang, Oliver Stöhr, Wei Qiu, Yue Hu, Ji Miao, X Charlie Dong, Sining Leng, Margaret Stefater, Nicholas Stylopoulos, Lin Lin, Kyle D Copps, Morris F White
Unsuppressed hepatic glucose production (HGP) contributes substantially to glucose intolerance and diabetes, which can be modeled by the genetic inactivation of hepatic insulin receptor substrate 1 (Irs1) and Irs2 (LDKO mice). We previously showed that glucose intolerance in LDKO mice is resolved by hepatic inactivation of the transcription factor FoxO1 (that is, LTKO mice)-even though the liver remains insensitive to insulin. Here, we report that insulin sensitivity in the white adipose tissue of LDKO mice is also impaired but is restored in LTKO mice in conjunction with normal suppression of HGP by insulin...
June 4, 2018: Nature Medicine
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