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Impaired glucose regulation

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https://www.readbyqxmd.com/read/28334808/downregulation-of-pathways-implicated-in-liver-inflammation-and-tumorigenesis-of-glycogen-storage-disease-type-ia-mice-receiving-gene-therapy
#1
Goo-Young Kim, Joon Hyun Kwon, Jun-Ho Cho, Lisa Zhang, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). We now show that in AAV-NT mice, the signaling pathways of the CR mediators, AMP-activated protein kinase (AMPK) and sirtuin-1 are activated...
March 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28333388/central-regulation-of-glucose-homeostasis
#2
Alexander Tups, Jonas Benzler, Domenico Sergi, Sharon R Ladyman, Lynda M Williams
The ability of the brain to directly control glucose levels in the blood independently of its effects on food intake and body weight has been known ever since 1854 when Claude Bernard, a French physiologist, discovered that lesioning the floor of the fourth ventricle in rabbits led to a rise of sugar in the blood. Despite this outstanding discovery at that time, it took more than 140 years before progress started to be made in identifying the underlying mechanisms of brain-mediated control of glucose homeostasis...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333211/glutathione-affects-the-transport-activity-of-rhizobium-leguminosarum-3841-and-is-essential-for-efficient-nodulation
#3
Guojun Cheng, Ramakrishnan Karunakaran, Alison K East, Olaya Munoz-Azcarate, Philip S Poole
As glutathione (GSH) plays an essential role in growth and symbiotic capacity of rhizobia, a glutathione synthetase (gshB) mutant of Rhizobium leguminosarum biovar viciae 3841 (Rlv3841) was characterised. It fails to efficiently utilise various compounds as a sole carbon source, including glucose, succinate, glutamine and histidine, and shows 60-69% reduction in uptake rates of glucose, succinate and the non-metabolisable substrate α-amino isobutyric acid (AIB). The defect in glucose uptake can be overcome by addition of exogenous GSH, indicating GSH, but not its bacterial synthesis, is required for efficient transport...
February 23, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28332581/elevated-mir-130a-mir130b-mir-152-expression-reduces-intracellular-atp-levels-in-the-pancreatic-beta-cell
#4
Jones K Ofori, Vishal A Salunkhe, Annika Bagge, Neelanjan Vishnu, Mototsugu Nagao, Hindrik Mulder, Claes B Wollheim, Lena Eliasson, Jonathan L S Esguerra
MicroRNAs have emerged as important players of gene regulation with significant impact in diverse disease processes. In type-2 diabetes, in which impaired insulin secretion is a major factor in disease progression, dysregulated microRNA expression in the insulin-secreting pancreatic beta cell has been widely-implicated. Here, we show that miR-130a-3p, miR-130b-3p, and miR-152-3p levels are elevated in the pancreatic islets of hyperglycaemic donors, corroborating previous findings about their upregulation in the islets of type-2 diabetes model Goto-Kakizaki rats...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28329397/resveratrol-improves-vascular-function-and-mitochondrial-number-but-not-glucose-metabolism-in-older-adults
#5
Rena M Pollack, Nir Barzilai, Valentin Anghel, Ameya S Kulkarni, Aaron Golden, Pilib O'Broin, David A Sinclair, Michael S Bonkowski, Alexander J Coleville, Danielle Powell, Sharon Kim, Ruin Moaddel, Daniel Stein, Kehao Zhang, Meredith Hawkins, Jill P Crandall
Background: Resveratrol, a plant-derived polyphenol, has been reported to improve glucose metabolism and vascular function and to extend life span in animal models, but studies in humans have been inconclusive. Methods: In a randomized, double-blind crossover study, we treated older glucose-intolerant adults (n = 30) with resveratrol (2-3 g/daily) or placebo, each for 6 weeks. A standard mixed-meal test was used to assess insulin sensitivity (Matsuda index) and secretion (C-peptide deconvolution) and vascular function by reactive hyperemia peripheral arterial tonometry...
March 16, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28327662/regulation-of-hepatic-lipogenesis-by-the-zinc-finger-protein-zbtb20
#6
Gan Liu, Luting Zhou, Hai Zhang, Rong Chen, Ye Zhang, Ling Li, Jun-Yu Lu, Hui Jiang, Dong Liu, Shasha Qi, Ying-Ming Jiang, Kai Yin, Zhifang Xie, Yuguang Shi, Yong Liu, Xuetao Cao, Yu-Xia Chen, Dajin Zou, Weiping J Zhang
Hepatic de novo lipogenesis (DNL) converts carbohydrates into triglycerides and is known to influence systemic lipid homoeostasis. Here, we demonstrate that the zinc finger protein Zbtb20 is required for DNL. Mice lacking Zbtb20 in the liver exhibit hypolipidemia and reduced levels of liver triglycerides, along with impaired hepatic lipogenesis. The expression of genes involved in glycolysis and DNL, including that of two ChREBP isoforms, is decreased in livers of knockout mice. Zbtb20 binds to and enhances the activity of the ChREBP-α promoter, suggesting that altered metabolic gene expression is mainly driven by ChREBP...
March 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28325479/the-role-of-pancreatic-preproglucagon-in-glucose-homeostasis-in-mice
#7
Adam P Chambers, Joyce E Sorrell, April Haller, Karen Roelofs, Chelsea R Hutch, Ki-Suk Kim, Ruth Gutierrez-Aguilar, Bailing Li, Daniel J Drucker, David A D'Alessio, Randy J Seeley, Darleen A Sandoval
Glucagon-like peptide 1 (GLP-1) is necessary for normal gluco-regulation, and it has been widely presumed that this function reflects the actions of GLP-1 released from enteroendocrine L cells. To test the relative importance of intestinal versus pancreatic sources of GLP-1 for physiological regulation of glucose, we administered a GLP-1R antagonist, exendin-[9-39] (Ex9), to mice with tissue-specific reactivation of the preproglucagon gene (Gcg). Ex9 impaired glucose tolerance in wild-type mice but had no impact on Gcg-null or GLP-1R KO mice, suggesting that Ex9 is a true and specific GLP-1R antagonist...
March 9, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28324053/hepatic-insulin-resistance-and-altered-gluconeogenic-pathway-in-premature-baboons
#8
Lisa McGill-Vargas, Amalia Gastaldelli, Hanyu Liang, Diana Anzueto Guerra, Teresa Johnson-Pais, Steven Seidner, Donald McCurnin, Giovanna Muscogiuri, Ralph DeFronzo, Nicolas Musi, Cynthia Blanco
Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extra-uterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content and gene expression of key insulin signaling/gluconeogenic molecules...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323968/impaired-glycine-mia-in-type-2-diabetes-and-potential-mechanisms-contributing-to-glucose-homeostasis
#9
Richard Yan-Do, Patrick E MacDonald
The onset and/or progression of type 2 diabetes (T2D) can be prevented if intervention is early enough. As such, much effort has been placed on the search for indicators predictive of pre-diabetes and disease onset or progression. An increasing body of evidence suggests that changes in plasma glycine may be one such biomarker. Circulating glycine levels are consistently low in patients with T2D. Levels of this non-essential amino acid correlate negatively with obesity and insulin resistance. Plasma glycine correlates positively with glucose disposal, and rises with interventions such as exercise and bariatric surgery that improve glucose homeostasis...
March 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323924/guanabenz-sensitizes-pancreatic-%C3%AE-cells-to-lipotoxic-endoplasmic-reticulum-stress-and-apoptosis
#10
Baroj Abdulkarim, Miriam Hernangomez, Mariana Igoillo Esteve, Daniel A Cunha, Lorella Marselli, Piero Marchetti, Laurence Ladriere, Miriam Cnop
Deficient as well as excessive/prolonged endoplasmic reticulum (ER) stress signaling can lead to pancreatic β cell failure and the development of diabetes. Saturated free fatty acids (FFAs) such as palmitate induce lipotoxic ER stress in pancreatic β cells. One of the main ER stress response pathways is under the control of the protein kinase R-like endoplasmic reticulum kinase (PERK), leading to phosphorylation of the eukaryotic translation initiation factor 2 (eIF2α). The antihypertensive drug guanabenz has been shown to inhibit eIF2α dephosphorylation and protect cells from ER stress...
March 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28314371/intrauterine-growth-restriction-programs-the-hypothalamus-of-adult-male-rats-integrated-analysis-of-proteomic-and-metabolomic-data
#11
Amanda Paula Pedroso, Adriana Pereira de Souza, Ana Paula Segantine Dornellas, Lila Missae Oyama, Cláudia Maria Oller Nascimento, Gianni Mara Silva Santos, José C Rosa, Ricardo Pimenta Bertolla, Jelena Klawitter, Uwe Christians, Alexandre Keiji Tashima, Eliane Beraldi Ribeiro
Programming of hypothalamic functions regulating energy homeostasis may play a role in intrauterine growth restriction (IUGR)-induced adulthood obesity. The present study investigated the effects of IUGR on the hypothalamus proteome and metabolome of adult rats submitted to 50% protein-energy restriction throughout pregnancy. Proteomic and metabolomic analyzes were performed by data independent acquisition mass spectrometry and multiple reaction monitoring, respectively. At age 4 months, the restricted rats showed elevated adiposity, increased leptin and signs of insulin resistance...
March 17, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28303919/eosinophils-are-key-regulators-of-perivascular-adipose-tissue-and-vascular-functionality
#12
Sarah B Withers, Ruth Forman, Selene Meza-Perez, Daniel Sorobetea, Kasia Sitnik, Thomas Hopwood, Catherine B Lawrence, William W Agace, Kathryn J Else, Anthony M Heagerty, Marcus Svensson-Frej, Sheena M Cruickshank
Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302757/alteration-of-monoamine-receptor-activity-and-glucose-metabolism-in-paediatric-patients-with-anticonvulsant-induced-cognitive-impairment
#13
Yuankai Zhu, Jianhua Feng, Jianfeng Ji, Haifeng Hou, Lin Chen, Shuang Wu, Qing Liu, Qiong Yao, Peizhen Du, Kai Zhang, Qing Chen, Zexin Chen, Hong Zhang, Mei Tian
A landmark study from the Institute of Medicine (IOM) reported that the assessment of cognitive difficulties in children with epilepsy is timely and imperative. Anticonvulsant-induced cognitive impairment could influence the quality of life more than seizure itself in patients. Although monoaminergic system is involved in the regulation of cognitive process, its role in anticonvulsant-induced cognitive impairment remains unclear. Methods: To explore in vivo monoamine receptor binding activity in patients with anticonvulsant-induced cognitive impairment, each patient had PET imaging with both monoamine receptor binding agent, (11)C-N-methylspiperone ((11)C-NMSP), and glucose metabolic agent, (18)F-fluorodeoxyglucose ((18)F-FDG)...
March 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28300563/sestrin-2-induces-autophagy-and-attenuates-insulin-resistance-by-regulating-ampk-signaling-in-c2c12-myotubes
#14
Huige Li, Sujuan Liu, Hairui Yuan, Yanmei Niu, Li Fu
Impaired insulin-stimulated glucose uptake in skeletal muscle serves a critical role in the development of insulin resistance (IR), whereas the precise mechanism of the process remains unknown. Recently, the evolutionarily conserved, stress-inducible protein Sestrin2 (Sesn2) has been proposed to play a protective role against obesity-induced IR and diabetes. Activation of Sesn2 may activate AMP-activated protein kinase (AMPK) accompanied by suppression of mammalian target of rapamycin (mTOR), which may ultimately lead to autophagy induction...
March 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28298335/hyperglycemia-and-hyperinsulinemia-induced-insulin-resistance-causes-alterations-in-cellular-bioenergetics-and-activation-of-inflammatory-signaling-in-lymphatic-muscle
#15
Yang Lee, James D Fluckey, Sanjukta Chakraborty, Mariappan Muthuchamy
Insulin resistance is a well-known risk factor for obesity, metabolic syndrome (MetSyn) and associated cardiovascular diseases, but its mechanisms are undefined in the lymphatics. Mesenteric lymphatic vessels from MetSyn or LPS-injected rats exhibited impaired intrinsic contractile activity and associated inflammatory changes. Hence, we hypothesized that insulin resistance in lymphatic muscle cells (LMCs) affects cell bioenergetics and signaling pathways that consequently alter contractility. LMCs were treated with different concentrations of insulin or glucose or both at various time points to determine insulin resistance...
March 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28294170/exploring-inter-organ-crosstalk-to-uncover-mechanisms-that-regulate-%C3%AE-cell-function-and-mass
#16
REVIEW
J Shirakawa, D F De Jesus, R N Kulkarni
Impaired β-cell function and insufficient β-cell mass compensation are twin pathogenic features that underlie type 2 diabetes (T2D). Current therapeutic strategies continue to evolve to improve treatment outcomes in different ethnic populations and include approaches to counter insulin resistance and improve β-cell function. Although the effects of insulin secretion on metabolic organs such as liver, skeletal muscle and adipose is directly relevant for improving glucose uptake and reduce hyperglycemia, the ability of pancreatic β-cells to crosstalk with multiple non-metabolic tissues is providing novel insights into potential opportunities for improving β-cell function and/or mass that could have beneficial effects in patients with diabetes...
March 15, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28292966/endothelial-hif-1%C3%AE-enables-hypothalamic-glucose-uptake-to-drive-pomc-neurons
#17
Luis Varela, Shigetomo Suyama, Yan Huang, Marya Shanabrough, Matthias H Tschoep, Xiao-Bing Gao, Frank J Giordano, Tamas L Horvath
Glucose is the primary driver of hypothalamic POMC neurons. Here, we show that endothelial HIF-1α controls glucose uptake in the hypothalamus, and, that it is up-regulated in conditions of under-nourishment during which POMC neuronal activity is decreased. Endothelium-specific knockdown of HIF-1α impairs the ability of POMC neurons to adapt to the changing metabolic environment in vivo resulting in overeating of mice after food deprivation. The impaired functioning of POMC neurons was reversed ex vivo or by parenchymal glucose administration...
March 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28289180/beneficial-effects-of-apelin-on-vascular-function-in-patients-with-central-obesity
#18
Francesca Schinzari, Augusto Veneziani, Nadia Mores, Angela Barini, Nicola Di Daniele, Carmine Cardillo, Manfredi Tesauro
Patients with central obesity have impaired insulin-stimulated vasodilation and increased ET-1 (endothelin 1) vasoconstriction, which may contribute to insulin resistance and vascular damage. Apelin enhances insulin sensitivity and glucose disposal but also acts as a nitric oxide (NO)-dependent vasodilator and a counter-regulator of AT1 (angiotensin [Ang] II type 1) receptor-induced vasoconstriction. We, therefore, examined the effects of exogenous (Pyr(1))apelin on NO-mediated vasodilation and Ang II- or ET-1-dependent vasoconstrictor tone in obese patients...
March 13, 2017: Hypertension
https://www.readbyqxmd.com/read/28280005/kcne2-deletion-impairs-insulin-secretion-and-causes-type-2-diabetes-mellitus
#19
Soo Min Lee, Jasmine Baik, Dara Nguyen, Victoria Nguyen, Shiwei Liu, Zhaoyang Hu, Geoffrey W Abbott
Type 2 diabetes mellitus (T2DM) represents a rapidly increasing threat to global public health. T2DM arises largely from obesity, poor diet, and lack of exercise, but it also involves genetic predisposition. Here we report that the KCNE2 potassium channel transmembrane regulatory subunit is expressed in human and mouse pancreatic β cells. Kcne2 deletion in mice impaired glucose tolerance as early as 5 wk of age in pups fed a Western diet, ultimately causing diabetes. In adult mice fed normal chow, skeletal muscle expression of insulin receptor β and insulin receptor substrate 1 were down-regulated 2-fold by Kcne2 deletion, characteristic of T2DM...
March 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28277032/novel-avenues-for-treating-diabetic-nephropathy-new-investigational-drugs
#20
Viviana Lacava, Vincenzo Pellicanò, Carmen Ferrajolo, Valeria Cernaro, Luca Visconti, Giovanni Conti, Michele Buemi, Domenico Santoro
At present, treatment of diabetic kidney disease (DKD) is still mainly based on drugs acting on glycemic and blood pressure control, as there is no validated therapy able to halt the progression of renal failure. Because of the high incidence of DKD, due to the increase of diabetes mellitus in general population, new therapeutic strategies are needed. Areas covered: We analysed ongoing and already completed clinical trials, from clinicaltrials.gov and PubMed, dealing with new therapies for DKD. Expert opinion: Among the drugs currently being explored, the most promising molecules are those that interfere with glucose-dependent pathways, in particular polyol, protein kinase, hexosamine and AGEs metabolic pathways, and impaired renal vascular regulation...
February 17, 2017: Expert Opinion on Investigational Drugs
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