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https://www.readbyqxmd.com/read/29046480/epigenetic-mechanisms-underlying-maternal-diabetes-associated-risk-of-congenital-heart-disease
#1
Madhumita Basu, Jun-Yi Zhu, Stephanie LaHaye, Uddalak Majumdar, Kai Jiao, Zhe Han, Vidu Garg
Birth defects are the leading cause of infant mortality, and they are caused by a combination of genetic and environmental factors. Environmental risk factors may contribute to birth defects in genetically susceptible infants by altering critical molecular pathways during embryogenesis, but experimental evidence for gene-environment interactions is limited. Fetal hyperglycemia associated with maternal diabetes results in a 5-fold increased risk of congenital heart disease (CHD), but the molecular basis for this correlation is unknown...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29045170/high-glucose-variability-in-hospitalized-patients-with-type-1-diabetes-mellitus
#2
Vikash Dadlani, Shrikant U Tamhane, Aidong Sun, Anu Sharma, Danae A Delivanis, Prabin Thapa, Ricky E Carter, Yogish C Kudva
BACKGROUND: Glucose variability (GV) has been increasingly (or more extensively) studied in patients with type 1 diabetes (T1D) in the ambulatory setting; limited data exist on GV in hospitalized patients with T1D. MATERIALS AND METHODS: Retrospective single center cohort study, we analyzed in-hospital glucose measurements to assess GV in 736 hospitalized patients in different units over a consecutive 5-year period of time. GV was assessed by mean blood glucose (BG), Average daily risk range (ADRR), high BG index, and low BG index...
October 2017: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/29044305/dysglycemia-in-the-critically-ill-patient-current-evidence-and-future-perspectives
#3
Ignacio Aramendi, Gastón Burghi, William Manzanares
Dysglycemia in critically ill patients (hyperglycemia, hypoglycemia, glycemic variability and time in range) is a biomarker of disease severity and is associated with higher mortality. However, this impact appears to be weakened in patients with previous diabetes mellitus, particularly in those with poor premorbid glycemic control; this phenomenon has been called "diabetes paradox". This phenomenon determines that glycated hemoglobin (HbA1c) values should be considered in choosing glycemic control protocols on admission to an intensive care unit and that patients' target blood glucose ranges should be adjusted according to their HbA1c values...
July 2017: Revista Brasileira de Terapia Intensiva
https://www.readbyqxmd.com/read/29038309/deletion-of-protein-kinase-d1-in-pancreatic-beta-cells-impairs-insulin-secretion-in-high-fat-fed-mice
#4
Valérie Bergeron, Julien Ghislain, Kevin Vivot, Natalia Tamarina, Louis H Philipson, Jens Fielitz, Vincent Poitout
Beta-cell adaptation to insulin resistance is necessary to maintain glucose homeostasis in obesity. Failure of this mechanism is a hallmark of type 2 diabetes (T2D). Hence, factors controlling functional beta-cell compensation are potentially important targets for the treatment of T2D. Protein kinase D1 (PKD1) integrates diverse signals in the beta cell and plays a critical role in the control of insulin secretion. However, the role of beta-cell PKD1 in glucose homeostasis in vivo is essentially unknown. Using beta-cell specific, inducible PKD1 knock-out mice (βPKD1KO), we examined the role of beta-cell PKD1 under basal conditions and during high-fat feeding...
October 16, 2017: Diabetes
https://www.readbyqxmd.com/read/29038248/lipopolysaccharide-potentiates-insulin-driven-hypoglycemic-shock
#5
Jon A Hagar, Matthew L Edin, Fred B Lih, Lance R Thurlow, Beverly H Koller, Bruce A Cairns, Darryl C Zeldin, Edward A Miao
Critically ill patients typically present with hyperglycemia. Treatment with conventional insulin therapy (targeting 144-180 mg/dl) improves patient survival; however, intensive insulin therapy (IIT) targeting normal blood glucose levels (81-108 mg/dl) increases the incidence of moderate and severe hypoglycemia, and increases mortality. Septic patients are especially prone to IIT-induced hypoglycemia, but the mechanism remains unknown. Here, we show that codelivery of insulin with otherwise sublethal doses of LPS induced hypoglycemic shock in mice within 1-2 h...
October 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29037594/epigenetic-modification-of-microrna-200b-contributes-to-diabetic-vasculopathy
#6
Kanhaiya Singh, Durba Pal, Mithun Sinha, Subhadip Ghatak, Surya C Gnyawali, Savita Khanna, Sashwati Roy, Chandan K Sen
Hyperglycemia (HG) induces genome-wide cytosine demethylation. Our previous work recognized miR-200b as a critical angiomiR, which must be transiently downregulated to initiate wound angiogenesis. Under HG, miR-200b downregulation is not responsive to injury. Here, we demonstrate that HG may drive vasculopathy by epigenetic modification of a miR promoter. In human microvascular endothelial cells (HMECs), HG also lowered DNA methyltransferases (DNMT-1 and DNMT-3A) and compromised endothelial function as manifested by diminished endothelial nitric oxide (eNOS), lowered LDL uptake, impaired Matrigel tube formation, lower NO production, and compromised VE-cadherin expression...
September 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29036909/diabetes-induced-dysfunction-of-mitochondria-and-stem-cells-in-skeletal-muscle-and-the-nervous-system
#7
REVIEW
Shin Fujimaki, Tomoko Kuwabara
Diabetes mellitus is one of the most common metabolic diseases spread all over the world, which results in hyperglycemia caused by the breakdown of insulin secretion or insulin action or both. Diabetes has been reported to disrupt the functions and dynamics of mitochondria, which play a fundamental role in regulating metabolic pathways and are crucial to maintain appropriate energy balance. Similar to mitochondria, the functions and the abilities of stem cells are attenuated under diabetic condition in several tissues...
October 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29032696/impact-of-improving-postprandial-glycemic-control-with-intensifying-insulin-therapy-in-type-2-diabetes
#8
Tamer Yacoub
Worldwide, many people with type 2 diabetes are not at recommended glycemic targets and remain at increased risk of microvascular and macrovascular complications. Reaching recommended glycemic targets requires normalizing both fasting and postprandial glucose (PPG). For some patients, this will require addition of a prandial insulin delivered by injection to control PPG excursions. Evidence from epidemiological studies suggests an association between postprandial hyperglycemia and cardiovascular disease, and thus, expert guidelines recommend that treatment for elevated PPG not be delayed...
October 14, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/29032153/metformin-overcomes-high-glucose-induced-insulin-resistance-of-podocytes-by-pleiotropic-effects-on-sirt1-and-ampk
#9
Dorota Rogacka, Irena Audzeyenka, Michał Rychłowski, Patrycja Rachubik, Maria Szrejder, Stefan Angielski, Agnieszka Piwkowska
Podocyte insulin sensitivity is critical for glomerular function, and the loss of appropriate insulin signaling leads to alterations and disorders featuring diabetic nephropathy. Energy-sensing pathways, such as AMP-dependent protein kinase (AMPK) and protein deacetylase SIRT1, have been shown to play an important role in insulin resistance. The absence of a stimulating effect of insulin on glucose uptake into podocytes after exposure to hyperglycemic conditions has been demonstrated to be related to a decreased level and activity of SIRT1 protein, leading to reduced AMPK phosphorylation...
October 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29031207/microrna-25-inhibits-high-glucose-induced-apoptosis-in-renal-tubular-epithelial-cells-via-pten-akt-pathway
#10
Huicong Li, Xiaoguang Zhu, Junwei Zhang, Jun Shi
Diabetic nephropathy (DN) has become the major cause of end-stage renal disease (ESRD). It has been demonstrated that apoptosis of renal tubular epithelial cells induced by hyperglycemia contributes to the pathogenesis of DN. Recent researches have corroborated the critical roles of microRNAs (miRNAs) in the apoptosis of various types of cells including renal tubular epithelial cells. However, the eff ; ;ect of miRNAs on the hyperglycemia-induced apoptosis of renal tubular epithelial cells remains unclear...
October 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29022064/proinflammatory-switch-from-g%C3%AE-s-to-g%C3%AE-i-signaling-by-glucagon-like-peptide-1-receptor-in-murine-splenic-monocyte-following-burn-injury
#11
Qing-Hong Zhang, Ji-Wei Hao, Guang-Lei Li, Xiao-Jing Ji, Xu-Dong Yao, Ning Dong, Yong-Ming Yao
OBJECTIVE: Glucagon-like peptide-1 (GLP-1)-based therapy via G protein-coupled receptor (GPCR) GLP-1R, to attenuate hyperglycemia in critical care has attracted great attention. However, the exaggerated inflammation by GLP-1R agonist, Exendin-4, in a mouse model of burn injury was quite unexpected. Recent studies found that GPCR might elicit proinflammatory effects by switching from Gαs to Gαi signaling in the immune system. Thus, we aimed to investigate the possible Gαs to Gαi switch in GLP-1R signaling in monocyte following burn injury...
October 11, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28994678/evaluation-of-the-effect-of-metformin-and-insulin-in-hyperglycemia-treatment-after-coronary-artery-bypass-surgery-in-nondiabetic-patients
#12
Kamran Ghods, Hossein Davari, Abbasali Ebrahimian
INTRODUCTION: Insulin therapy is the most commonly used treatment for controlling hyperglycemia after coronary artery bypass surgery in both diabetic and nondiabetic patients. Metformin has been indicated for critically ill patients as an alternate for the treatment of hyperglycemia. This study evaluated the effect of metformin and insulin in hyperglycemia treatment after coronary artery bypass surgery in nondiabetic patients. SETTINGS AND DESIGN: This study was a clinical trial comprising nondiabetic patients who had undergone coronary artery bypass surgery...
October 2017: Annals of Cardiac Anaesthesia
https://www.readbyqxmd.com/read/28993702/erv1-overexpression-in-myeloid-cells-protects-against-high-fat-diet-induced-obesity-and-glucose-intolerance
#13
Corneliu Sima, Eduardo Montero, Daniel Nguyen, Marcelo Freire, Paul Norris, Charles N Serhan, Thomas E Van Dyke
Non-resolving inflammation is a central pathologic component of obesity, insulin resistance, type 2 diabetes and associated morbidities. The resultant hyperglycemia is deleterious to the normal function of many organs and its control significantly improves survival and quality of life for patients with diabetes. Macrophages play critical roles in both onset and progression of obesity-associated insulin resistance. Here we show that systemic activation of inflammation resolution prevents from morbid obesity and hyperglycemia under dietary overload conditions...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28989027/hyperglycemic-condition-during-puberty-increases-collagen-fibers-deposition-in-the-prostatic-stroma-and-reduces-mmp-2-activity
#14
Sérgio Alexandre Alcantara Dos Santos, Elaine Manoela Porto Amorim, Larissa Mayume Ribeiro, Jaqueline Carvalho Rinaldi, Flávia Karina Delella, Luis Antonio Justulin, Sérgio Luis Felisbino
Puberty is an important period for the growth and maturation of the male reproductive system, and is also a critical window for endocrine or environmental interference. The physiological levels of circulating insulin and hyperglycemic control are important factors for a normal prostate growth. Hyperglycemia during puberty is reported to retard the growth of the prostate gland, with remarkable effects on the epithelial compartment. Here, we investigated the impact of hyperglycemia along with a simultaneous or late insulin replacement on the ventral prostate growth in rats during puberty, paying special attention to the deposition of collagen fibers and activities of gelatinase, matrix metalloproteinase-2 (MMP-2), and -9 (MMP-9)...
October 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28985843/total-parenteral-nutrition-in-patients-following-pancreaticoduodenectomy-lessons-from-1184-patients
#15
Cullen E Worsh, Talar Tatarian, Awinder Singh, Michael J Pucci, Jordan M Winter, Charles J Yeo, Harish Lavu
BACKGROUND: Total parenteral nutrition (TPN) has historically been used conservatively in the management of patients after pancreaticoduodenectomy (PD). Herein, we evaluate the indications for and outcomes associated with TPN use in a high-volume pancreatic surgery center. MATERIALS AND METHODS: We retrospectively queried our institution's pancreatic surgery database for patients who received TPN after PD from 2006 through 2015. RESULTS: Of 1184 patients who underwent PD, 232 (19...
October 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28982613/klotho-protects-the-heart-from-hyperglycemia-induced-injury-by-inactivating-ros-and-nf-%C3%AE%C2%BAb-mediated-inflammation-both-in-vitro-and-in-vivo
#16
Yue Guo, Xiaodong Zhuang, Zena Huang, Jing Zou, Daya Yang, Xun Hu, Zhimin Du, Lichun Wang, Xinxue Liao
Cardiac inflammation and oxidative stress play a key role in the pathogenesis of diabetic cardiomyopathy (DCM). The anti-aging protein Klotho has been found to protect cells from inflammation and oxidative stress. The current study aimed to explore the cardioprotective effects of Klotho on DCM and the underlying mechanisms. H9c2 cells and neonatal cardiomyocytes were incubated with 33mM glucose in the presence or absence of Klotho. Klotho pretreatment effectively inhibited high glucose-induced inflammation, ROS generation, apoptosis, mitochondrial dysfunction, fibrosis and hypertrophy in both H9c2 cells and neonatal cardiomyocytes...
October 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28976790/phosphatidylinositol-3-kinase-inhibition-by-copanlisib-in-relapsed-or-refractory-indolent-lymphoma
#17
Martin Dreyling, Armando Santoro, Luigina Mollica, Sirpa Leppä, George A Follows, Georg Lenz, Won Seog Kim, Arnon Nagler, Panayiotis Panayiotidis, Judit Demeter, Muhit Özcan, Marina Kosinova, Krimo Bouabdallah, Franck Morschhauser, Don A Stevens, David Trevarthen, Marius Giurescu, Lisa Cupit, Li Liu, Karl Köchert, Henrik Seidel, Carol Peña, Shuxin Yin, Florian Hiemeyer, Jose Garcia-Vargas, Barrett H Childs, Pier Luigi Zinzani
Purpose Phosphatidylinositol 3-kinase (PI3K) signaling is critical for the proliferation and survival of malignant B cells. Copanlisib, a pan-class I PI3K inhibitor with predominant activity against PI3K-α and -δ isoforms, has demonstrated efficacy and a manageable safety profile in patients with indolent lymphoma. Patients and Methods In this phase II study, 142 patients with relapsed or refractory indolent lymphoma after two or more lines of therapy were enrolled to receive copanlisib 60 mg intravenously on days 1, 8, and 15 of a 28-day cycle...
October 4, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28975464/peroxynitrite-induced-tyrosine-nitration-contributes-to-matrix-metalloprotease-3-activation-relevance-to-hyperglycemic-ischemic-brain-injury-and-tissue-plasminogen-activator
#18
Sherif Hafez, Mohammed Abdelsaid, Susan C Fagan, Adviye Ergul
Matrix metalloprotease-3 (MMP3) activation mediates the tissue plasminogen activator (tPA)-induced hemorrhagic transformation after stroke. Hyperglycemia (HG) further exacerbates this outcome. We have recently shown that HG increases MMP3 activity in the brain after stroke. However, the combined HG-tPA effect on MMP3 activation, and the mechanisms through which MMP3 is activated were not previously reported. Accordingly, this study tested the hypothesis that tPA and HG increases MMP3 activity in the brain after stroke through peroxynitrite induced tyrosine nitration...
October 3, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28954230/fumarate-hydratase-deletion-in-pancreatic-%C3%AE-cells-leads-to-progressive-diabetes
#19
Julie Adam, Reshma Ramracheya, Margarita V Chibalina, Nicola Ternette, Alexander Hamilton, Andrei I Tarasov, Quan Zhang, Eduardo Rebelato, Nils J G Rorsman, Rafael Martín-Del-Río, Amy Lewis, Gizem Özkan, Hyun Woong Do, Peter Spégel, Kaori Saitoh, Keiko Kato, Kaori Igarashi, Benedikt M Kessler, Christopher W Pugh, Jorge Tamarit-Rodriguez, Hindrik Mulder, Anne Clark, Norma Frizzell, Tomoyoshi Soga, Frances M Ashcroft, Andrew Silver, Patrick J Pollard, Patrik Rorsman
We explored the role of the Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 in pancreatic β cells (Fh1βKO mice) appear normal for 6-8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1α or Nrf2. Progressive hyperglycemia in Fh1βKO mice led to dysregulated metabolism in β cells, a decrease in glucose-induced ATP production, electrical activity, cytoplasmic [Ca(2+)]i elevation, and GSIS...
September 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/28935429/glycemic-control-in-patients-undergoing-coronary-artery-bypass-graft-surgery-clinical-features-predictors-and-outcomes
#20
Judson B Williams, Eric D Peterson, Álvaro S Albrecht, Shuang Li, Sameer A Hirji, T Ferguson, Peter K Smith, Renato D Lopes
PURPOSE: Critically ill patients with hyperglycemia have worse prognosis. The degree to which glycemic control is achieved following CABG surgery and the association with clinical outcomes is not well understood. MATERIALS AND METHODS: We studied patients undergoing higher risk CABG surgery at 55 US hospitals. Good glycemic control was defined as 70-180mg/dL in the first 24h postoperatively. Generalized estimating equations logistic regression models were used to assess the relationship between glycemic control and clinical outcomes after adjusting for baseline characteristics...
September 9, 2017: Journal of Critical Care
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