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https://www.readbyqxmd.com/read/29768504/sarcopoterium-spinosum-extract-improved-insulin-sensitivity-in-mice-models-of-glucose-intolerance-and-diabetes
#1
Konstantin Rozenberg, Tovit Rosenzweig
BACKGROUND: The glucose lowering properties of Sarcopoterium spinosum, a traditional medicinal plant, were previously validated by us using KK-Ay mice as a genetic model for type 2 diabetes (T2D). OBJECTIVE: To clarify the effects of Sarcopoterium spinosum extract (SSE) on diet-induced glucose intolerance and to investigate SSE effects on carbohydrate and lipid metabolism in target tissues of both high-fat-diet (HFD)-fed and KK-Ay mice. RESULTS: Mice were given SSE (70 mg/day) for 6 weeks...
2018: PloS One
https://www.readbyqxmd.com/read/29758564/monogenic-diabetes-in-overweight-and-obese-youth-diagnosed-with-type-2-diabetes-the-today-clinical-trial
#2
Jeffrey W Kleinberger, Kenneth C Copeland, Rachelle G Gandica, Morey W Haymond, Lynne L Levitsky, Barbara Linder, Alan R Shuldiner, Sherida Tollefsen, Neil H White, Toni I Pollin
PurposeMonogenic diabetes accounts for 1-2% of diabetes cases. It is often undiagnosed, which may lead to inappropriate treatment. This study was performed to estimate the prevalence of monogenic diabetes in a cohort of overweight/obese adolescents diagnosed with type 2 diabetes (T2D).MethodsSequencing using a custom monogenic diabetes gene panel was performed on a racially/ethnically diverse cohort of 488 overweight/obese adolescents with T2D in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial...
October 12, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29753302/contribution-of-hepatic-retinaldehyde-dehydrogenase-induction-to-impairment-of-glucose-metabolism-by-high-fat-diet-feeding-in-c57bl-6j-mice
#3
Jiong Xu, Mian Zhang, Xiangping Zhang, Hanyu Yang, Binbin Sun, Zhongjian Wang, Yaqian Zhou, Shuting Wang, Xiaodong Liu, Li Liu
Obesity and insulin resistance are associated with overexpression of retinaldehyde dehydrogenase 1 (RALDH1). We aimed to investigate the roles of hepatic RALDH1 induction in glucose metabolism impairment using mice fed with high-fat diet (HFD). Mice were fed with HFD for 8 weeks and treated with RALDH inhibitor citral for another 4 weeks. Oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT) and insulin tolerance test (ITT) were operated. Expressions of Phosphoenolpyruvate carboxykinase 1 (PCK1), glucokinase (GCK) and RALDH1 were measured...
May 12, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29728018/-analysis-on-component-target-pathway-of-paeonia-lactiflora-in-treating-cardiac-diseases-based-on-data-mining
#4
Yang Liu, Fang-Bo Zhang, Shi-Huan Tang, Ping Wang, Sen Li, Jin Su, Rong-Rong Zhou, Jia-Qi Zhang, Hui-Feng Sun
Based on the literature review and modern application of Paeonia lactiflora in heart diseases, this article would predict the target of drug and disease by intergrative pharmacology platform of traditional Chinese medicine (TCMIP, http://www.tcmip.cn), and then explore the molecular mechanism of P. lactiflora in treatment of heart disease, providing theoretical basis and method for further studies on P. lactiflora. According to the ancient books, P. lactiflora with functions of "removing the vascular obstruction, removing the lumps, relieving pain, diuretic, nutrient qi" and other effects, have been used for many times to treat heart disease...
April 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29726111/clinical-usefulness-of-comprehensive-genetic-screening-in-mody-a-novel-abcc8-mutation-in-a-previously-screened-family
#5
Stephanie Robyn Johnson, Paul Leo, Louise Sonia Conwell, Mark Harris, Matthew Arthur Brown, Emma Letitia Duncan
Maturity-onset diabetes of the young (MODY) is the commonest form of monogenic diabetes, resulting from dominant mutations in one of fourteen genes that regulate beta-cell function (HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8,KCNJ11 and APPL1 1,2 ). MODY accounts for 2-2.5% of childhood diabetes 3 , yet MODY genetic screening is uncommon, even in highly suggestive families, and when performed often limited to the commonest genes (e.g.HNF1A and GCK) 4 .
May 4, 2018: Journal of Diabetes
https://www.readbyqxmd.com/read/29717618/glucocorticoid-signaling-enhances-expression-of-glucose-sensing-molecules-in-immature-pancreatic-beta-like-cells-derived-from-murine-embryonic-stem-cells-in-vitro
#6
Nadiah Ghazalli, Xiaoxing Wu, Stephanie Walker, Nancy Trieu, Li-Yu Hsin, Justin Choe, Chialin Chen, Jasper Hsu, Jeanne LeBon, Mark T Kozlowski, Jeffrey Rawson, David A Tirrell, M L Richard Yip, Hsun Teresa Ku
Pluripotent stem cells may serve as an alternative source of beta-like cells for replacement therapy of type 1 diabetes; however, the beta-like cells generated in many differentiation protocols are immature. The maturation of endogenous beta cells involves an increase in insulin expression starting in late gestation and a gradual acquisition of the abilities to sense glucose and secrete insulin by week 2 after birth in mice; however, what molecules regulate these maturation processes are incompletely known...
May 2, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29716943/hepatic-glucose-metabolic-responses-to-digestible-dietary-carbohydrates-in-two-isogenic-lines-of-rainbow-trout
#7
X Song, L Marandel, M Dupont-Nivet, E Quillet, I Geurden, S Panserat
Rainbow trout ( Oncorhynchus mykiss ) was recognized as typical "glucose-intolerant" fish and poor dietary carbohydrate user. Our first objective was to test the effect of dietary carbohydrates itself (without modification of dietary protein intake) on hepatic glucose gene expression (taking into account of the paralogs. The second aim was to research if two isogenic trout lines had different responds to carbohydrate intake, showing one with a better use dietary carbohydrates. Thus, we used two isogenic lines of rainbow trout (named A32h and AB1h) fed with either high carbohydrate diet or low carbohydrate diet for 12 weeks...
May 1, 2018: Biology Open
https://www.readbyqxmd.com/read/29704611/functional-characterization-of-mody2-mutations-in-the-nuclear-export-signal-of-glucokinase
#8
Angel Gutierrez-Nogués, Carmen-María García-Herrero, Josep Oriola, Olivier Vincent, María-Angeles Navas
Glucokinase (GCK) plays a key role in glucose homeostasis. Heterozygous inactivating mutations in the GCK gene cause the familial, mild fasting hyperglycaemia named MODY2. Besides its particular kinetic characteristics, glucokinase is regulated by subcellular compartmentation in hepatocytes. Glucokinase regulatory protein (GKRP) binds to GCK, leading to enzyme inhibition and import into the nucleus at fasting. When glucose concentration increases, GCK-GKRP dissociates and GCK is exported to the cytosol due to a nuclear export signal (NES)...
July 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29681858/aqueous-extract-of-black-maca-prevents-metabolism-disorder-via-regulating-the-glycolysis-gluconeogenesis-tca-cycle-and-ppar%C3%AE-signaling-activation-in-golden-hamsters-fed-a-high-fat-high-fructose-diet
#9
Wenting Wan, Hongxiang Li, Jiamei Xiang, Fan Yi, Lijia Xu, Baoping Jiang, Peigen Xiao
Maca ( Lepidium meyenii Walpers) has been used as a dietary supplement and ethnomedicine for centuries. Recently, maca has become a high profile functional food worldwide because of its multiple biological activities. This study is the first explorative research to investigate the prevention and amelioration capacity of the aqueous extract of black maca (AEM) on high-fat, high-fructose diet (HFD)-induced metabolism disorder in golden hamsters and to identify the potential mechanisms involved in these effects...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29621497/arsenic-gene-interactions-and-beta-cell-function-in-the-strong-heart-family-study
#10
Poojitha Balakrishnan, Ana Navas-Acien, Karin Haack, Dhananjay Vaidya, Jason G Umans, Lyle G Best, Walter Goessler, Kevin A Francesconi, Nora Franceschini, Kari E North, Shelley A Cole, V Saroja Voruganti, Matthew O Gribble
We explored arsenic-gene interactions influencing pancreatic beta-cell activity in the Strong Heart Family Study (SHFS). We considered 42 variants selected for associations with either beta-cell function (31 variants) or arsenic metabolism (11 variants) in the SHFS. Beta-cell function was calculated as homeostatic model - beta corrected for insulin resistance (cHOMA-B) by regressing homeostatic model - insulin resistance (HOMA-IR) on HOMA-B and adding mean HOMA-B. Arsenic exposure was dichotomized at the median of the sum of creatinine-corrected inorganic and organic arsenic species measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS)...
April 2, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29620215/integrated-analysis-of-the-gene-expression-profile-and-dna-methylation-profile-of-obese-patients-with-type-2-diabetes
#11
Juan Shen, Bin Zhu
In order to better understand the etiology of obese type 2 diabetes (T2D) at the molecular level, the present study investigated the gene expression and DNA methylation profiles associated with T2D via systemic analysis. Gene expression (GSE64998) and DNA methylation profiles (GSE65057) from liver tissues of healthy controls and obese patients with T2D were downloaded from the Gene Expression Omnibus database. Differentially‑expressed genes (DEGs) and differentially‑methylated genes (DMGs) were identified using the Limma package, and their overlapping genes were additionally determined...
March 28, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29573377/the-two-major-glucokinase-isoforms-show-conserved-functionality-in-%C3%AE-cells-despite-different-subcellular-distribution
#12
Brian Lu, Miguel Munoz-Gomez, Yasuhiro Ikeda
Glucokinase (GCK) is crucial to regulating glucose metabolism in the liver and in pancreatic β-cells. There are two major GCK isoforms, hepatic and pancreatic GCKs, which differ only in exon 1. However, the functional differences between the two GCK isoforms remain poorly understood. Here, we used a β-cell-targeted gene transfer vector to determine the impact of isoform-specific GCK overexpression on β-cells in vitro and in vivo. We showed that pancreatic GCK had a nuclear localization signal unique to the pancreatic isoform, facilitating its nuclear distribution in β-cells...
March 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29546446/cyp3a4-and-gck-genetic-polymorphisms-are-the-risk-factors-of-tacrolimus-induced-new-onset-diabetes-after-transplantation-in-renal-transplant-recipients
#13
Daohua Shi, Tiancheng Xie, Jie Deng, Peiguang Niu, Weizhen Wu
PURPOSE: We intend to investigate the association between tacrolimus-induced new-onset diabetes after transplantation (NODAT) and polymorphisms of CYP3A4, CYP3A5, ATP-binding cassette transporter sub-family C member 8 (ABCC8), and glucokinase (GCK) in renal transplant recipients. METHODS: Polymorphisms of CYP3A4 *18B, CYP3A5 *3, ABCC8 T-3C, and GCK G-30A were genotyped in 169 renal transplant recipients. Trough concentrations of tacrolimus were detected by an ELISA kit...
March 15, 2018: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29544862/the-role-of-glucokinase-and-insulin-receptor-substrate-2-in-the-proliferation-of-pancreatic-beta-cells-induced-by-short-term-high-fat-diet-feeding-in-mice
#14
Naoyuki Kitao, Akinobu Nakamura, Hideaki Miyoshi, Hiroshi Nomoto, Kiyohiko Takahashi, Kazuno Omori, Kohei Yamamoto, Kyu Yong Cho, Yasuo Terauchi, Tatsuya Atsumi
OBJECTIVE: We investigated whether glucokinase and insulin receptor substrate-2 were required for beta cell proliferation induced by short-term high-fat (HF) diet feeding, as has been shown for long-term HF diet. METHODS: Eight-week-old C57BL/6 J mice were exposed to either a standard chow (SC) or HF diet. After 1 week on the diet, histopathological beta cell proliferation and gene expression in isolated islets were examined. Additionally, 8-week-old beta cell-specific glucokinase haploinsufficient (Gck+/- ) and Irs2 knockout (Irs2-/- ) mice were exposed to either an SC or HF diet...
March 12, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29510678/genetic-and-clinical-characteristics-of-chinese-children-with-glucokinase-maturity-onset-diabetes-of-the-young-gck-mody
#15
Xiuzhen Li, Tzer Hwu Ting, Huiying Sheng, Cui Li Liang, Yongxian Shao, Minyan Jiang, Aijing Xu, Yunting Lin, Li Liu
BACKGROUND: There is scarcity of information on the clinical features and genetics of glucokinase-maturity-onset diabetes of the young (GCK-MODY) in China. The aim of the study was to investigate the clinical and molecular characteristics of Chinese children with GCK-MODY. METHODS: Eleven children with asymptomatic hyperglycemia and clinically suspected GCK-MODY were identified from the database of children with diabetes in the biggest children's hospital in South China...
March 6, 2018: BMC Pediatrics
https://www.readbyqxmd.com/read/29493090/clinical-heterogeneity-of-hyperinsulinism-due-to-hnf1a-and-hnf4a-mutations
#16
Joanna Yuet-Ling Tung, Kara Boodhansingh, Charles A Stanley, Diva D De León
BACKGROUND: Dominant inactivating mutations in HNF1A and HNF4A have been described to cause hyperinsulinism (HI) before evolving to diabetes. However, information available in the literature regarding the clinical phenotype is limited. OBJECTIVE: To report the prevalence of HNF1A and HNF4A mutations in a large cohort of children with HI, and to describe their genotypes and phenotypes. DESIGN: Retrospective descriptive study. METHODS: Medical records were reviewed to extract clinical information...
March 1, 2018: Pediatric Diabetes
https://www.readbyqxmd.com/read/29483669/genetic-determinants-of-glycated-hemoglobin-levels-in-the-greenlandic-inuit-population
#17
Emil V R Appel, Ida Moltke, Marit E Jørgensen, Peter Bjerregaard, Allan Linneberg, Oluf Pedersen, Anders Albrechtsen, Torben Hansen, Niels Grarup
We previously showed that a common genetic variant leads to a remarkably increased risk of type 2 diabetes (T2D) in the small and historically isolated Greenlandic population. Motivated by this, we aimed at discovering novel genetic determinants for glycated hemoglobin (HbA1C ) and at estimating the effect of known HbA1C -associated loci in the Greenlandic population. We analyzed genotype data from 4049 Greenlanders generated using the Illumina Cardio-Metabochip. We performed the discovery association analysis by an additive linear mixed model...
February 26, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29476712/progressive-glomerular-and-tubular-damage-in-sickle-cell-trait-and-sickle-cell-anemia-mouse-models
#18
Santosh L Saraf, Justin R Sysol, Alexandru Susma, Suman Setty, Xu Zhang, Krishnamurthy P Gudehithlu, Jose A L Arruda, Ashok K Singh, Roberto F Machado, Victor R Gordeuk
Homozygosity for the hemoglobin (Hb) S mutation (HbSS, sickle cell anemia) results in hemoglobin polymerization under hypoxic conditions leading to vaso-occlusion and hemolysis. Sickle cell anemia affects 1:500 African Americans and is a strong risk factor for kidney disease, although the mechanisms are not well understood. Heterozygous inheritance (HbAS; sickle cell trait) affects 1:10 African Americans and is associated with an increased risk for kidney disease in some reports. Using transgenic sickle mice, we investigated the histopathologic, ultrastructural, and gene expression differences with the HbS mutation...
February 2, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29475461/eugenosedin-a-improves-glucose-metabolism-and-inhibits-mapks-expression-in-streptozotocin-nicotinamide-induced-diabetic-rats
#19
Kuo-Ping Shen, Hui-Li Lin, Hsueh-Wei Yen, Su-Ling Hsieh, Li-Mei An, Bin-Nan Wu
This study examined the effects of eugenosedin-A (Eu-A) in a streptozotocin (STZ)/nicotinamide-induced rat model of type II diabetes mellitus (T2DM). Six-week-old Sprague-Dawley rats were randomly divided into three groups: (1) RD group, normal rats fed a regular diet (RD), (2) DM group, T2DM rats fed a high-fat diet, and (3) Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day). After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group...
March 2018: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/29472102/modeling-human-pancreatic-beta-cell-dedifferentiation
#20
Marc Diedisheim, Masaya Oshima, Olivier Albagli, Charlotte Wennberg Huldt, Ingela Ahlstedt, Maryam Clausen, Suraj Menon, Alexander Aivazidis, Anne-Christine Andreasson, William G Haynes, Piero Marchetti, Lorella Marselli, Mathieu Armanet, Fabrice Chimienti, Raphael Scharfmann
OBJECTIVE: Dedifferentiation could explain reduced functional pancreatic β-cell mass in type 2 diabetes (T2D). METHODS: Here we model human β-cell dedifferentiation using growth factor stimulation in the human β-cell line, EndoC-βH1, and human pancreatic islets. RESULTS: Fibroblast growth factor 2 (FGF2) treatment reduced expression of β-cell markers, (INS, MAFB, SLC2A2, SLC30A8, and GCK) and activated ectopic expression of MYC, HES1, SOX9, and NEUROG3...
April 2018: Molecular Metabolism
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