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https://www.readbyqxmd.com/read/28343277/pancreatic-alpha-cell-selective-deletion-of-tcf7l2-impairs-glucagon-secretion-and-counter-regulatory-responses-to-hypoglycaemia-in-mice
#1
Gabriela da Silva Xavier, Angeles Mondragon, Vishnou Mourougavelou, Céline Cruciani-Guglielmacci, Jessica Denom, Pedro Luis Herrera, Christophe Magnan, Guy A Rutter
AIMS/HYPOTHESIS: Transcription factor 7-like 2 (TCF7L2) is a high mobility group (HMG) box-containing transcription factor and downstream effector of the Wnt signalling pathway. SNPs in the TCF7L2 gene have previously been associated with an increased risk of type 2 diabetes in genome-wide association studies. In animal studies, loss of Tcf7l2 function is associated with defective islet beta cell function and survival. Here, we explore the role of TCF7L2 in the control of the counter-regulatory response to hypoglycaemia by generating mice with selective deletion of the Tcf7l2 gene in pancreatic alpha cells...
March 25, 2017: Diabetologia
https://www.readbyqxmd.com/read/28342971/a-novel-dual-glp-1-gip-receptor-agonist-alleviates-cognitive-decline-by-re-sensitizing-insulin-signaling-in-the-alzheimer-icv-stz-rat-model
#2
Lijuan Shi, Zhihua Zhang, Lin Li, Christian Hölscher
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, accompanied by memory loss and cognitive impairments, and there is no effective treatment for it at present. Since type 2 diabetes (T2DM) has been identified as a risk factor for AD, the incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), promising antidiabetic agents for the treatment of type 2 diabetes, have been tested in models of neurodegenerative disease including AD and achieved good results...
March 22, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28342850/structural-basis-for-differential-activities-of-enantiomeric-ppar%C3%AE-agonists-binding-of-s35-to-the-alternate-site
#3
Jun Young Jang, Minseob Koh, Hwan Bae, Doo Ri An, Ha Na Im, Hyoun Sook Kim, Ji Young Yoon, Hye-Jin Yoon, Byung Woo Han, Seung Bum Park, Se Won Suh
Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, type 2 diabetes mellitus, and inflammation. Many PPARγ agonists bind to the canonical ligand-binding pocket near the activation function-2 (AF-2) helix (i.e., helix H12) of the ligand-binding domain (LBD). More recently, an alternate ligand-binding site was identified in PPARγ LBD; it is located beside the Ω loop between the helices H2' and H3...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342842/protectin-dx-suppresses-hepatic-gluconeogenesis-through-ampk-ho-1-mediated-inhibition-of-er-stress
#4
Tae Woo Jung, Hyung-Chun Kim, Ji Hoon Jeong
Several studies have shown that protectins, which are ω-3 fatty acid-derived proresolution mediators, may improve insulin resistance. Recently, protectin DX (PDX) was documented to attenuate insulin resistance by stimulating IL-6 expression in skeletal muscle, thereby regulating hepatic gluconeogenesis. These findings made us investigate the direct effects of PDX on hepatic glucose metabolism in the context of diabetes. In the current study, we show that PDX regulates hepatic gluconeogenesis in a manner distinct from its indirect glucoregulatory activity via IL-6...
March 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28342603/invited-review-the-anti-inflammatory-properties-of-dairy-lipids
#5
R Lordan, I Zabetakis
Dairy product consumption is often associated with negative effects because of its naturally high levels of saturated fatty acids. However, recent research has shown that dairy lipids possess putative bioactivity against chronic inflammation. Inflammation triggers the onset of several chronic diseases, including cardiovascular disease, type 2 diabetes mellitus, obesity, and cancer. This review discusses the anti-inflammatory properties of dairy lipids found in milk, yogurt, and cheese, and it examines them in relation to their implications for human health: their protective effects and their role in pathology...
March 22, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28342563/type-2-diabetes-mellitus-treatment-patterns-across-europe-a-population-based-multi-database-study
#6
Jetty A Overbeek, Edith M Heintjes, Daniel Prieto-Alhambra, Patrick Blin, Régis Lassalle, Gillian C Hall, Francesco Lapi, Elisa Bianchini, Niklas Hammar, Irene D Bezemer, Ron M C Herings
PURPOSE: The aim of this study was to determine the similarities and differences of type 2 diabetes mellitus (T2DM) treatment patterns in daily practice in 5 European countries and whether these reflect differences in guidelines. METHODS: Prescriptions for drugs used in diabetes treatment during a 5-year study period were obtained from electronic databases. Patients initiating T2DM treatment during the study period were included. An SAS analysis tool was developed to create episodes of use of drug classes, which resulted in treatment patterns...
March 22, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28342399/design-synthesis-and-biological-evaluation-of-pegylated-xenopus-glucagon-like-peptide-1-derivatives-as-long-acting-hypoglycemic-agents
#7
Jing Han, Yiyun Wang, Qinghua Meng, Guangchao Li, Fangmin Huang, Su Wu, Yingying Fei, Feng Zhou, Junjie Fu
In order to develop novel long-acting GLP-1 derivatives, a peptide hybrid (1a) from human GLP-1 and Xenopus GLP-1 discovered in our previous research was selected as the lead compound. Exendin-4 inspired modification resulted in peptide 1b with enhanced glucose-lowering activity. Cysteine mutated 1b derivatives with reserved bioactivity were further site-specifically connected with mPEG2000-MAL to provide conjugates 3a-h, among which 3d and 3e were found to have significantly improved hypoglycemic activity and insulinotropic ability than GLP-1...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28340360/the-influence-of-carbohydrate-consumption-on-glycemic-control-in-pregnant-women-with-type-1-diabetes
#8
Björg Ásbjörnsdóttir, Cecelia E Akueson, Helle Ronneby, Ane Rytter, Jens R Andersen, Peter Damm, Elisabeth R Mathiesen
AIMS: To study the influence of the quantity and the quality of carbohydrate consumption on glycemic control in early pregnancy among women with type 1 diabetes. METHODS: A retrospective study of 107 women with type 1 diabetes who completed 1-3days of diet recording before first antenatal visit, as a part of routine care. The total daily carbohydrate consumption from the major sources (e.g. bread, potatoes, rice, pasta, dairy products, fruits, candy) was calculated...
December 23, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28340340/selective-chemical-inhibition-of-pgc-1%C3%AE-gluconeogenic-activity-ameliorates-type-2-diabetes
#9
Kfir Sharabi, Hua Lin, Clint D J Tavares, John E Dominy, Joao Paulo Camporez, Rachel J Perry, Roger Schilling, Amy K Rines, Jaemin Lee, Marc Hickey, Melissa Bennion, Michelle Palmer, Partha P Nag, Joshua A Bittker, José Perez, Mark P Jedrychowski, Umut Ozcan, Steve P Gygi, Theodore M Kamenecka, Gerald I Shulman, Stuart L Schreiber, Patrick R Griffin, Pere Puigserver
Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340221/nationwide-multicentre-kidney-biopsy-study-of-japanese-patients-with-type-2-diabetes
#10
Kengo Furuichi, Yukio Yuzawa, Miho Shimizu, Akinori Hara, Tadashi Toyama, Hiroshi Kitamura, Yoshiki Suzuki, Hiroshi Sato, Noriko Uesugi, Yoshifumi Ubara, Satoshi Hisano, Yoshihiko Ueda, Shinichi Nishi, Hitoshi Yokoyama, Tomoya Nishino, Kentaro Kohagura, Daisuke Ogawa, Koki Mise, Yugo Shibagaki, Kenjiro Kimura, Masakazu Haneda, Hirofumi Makino, Seiichi Matsuo, Takashi Wada
Background.: The clinical and pathologic manifestations of nephropathy due to type 2 diabetes are diverse, but large-scale pathologic studies with long-term observations are limited. Methods.: Kidney biopsies and clinical data of 600 patients with type 2 diabetes were collected retrospectively from 13 centres across Japan. Thirteen pathologic findings (nine glomerular lesions, two interstitial lesions and two vascular lesions) were clearly defined and scored. Results...
March 2, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28340087/nutrigenomic-point-of-view-on-effects-and-mechanisms-of-action-of-ruminant-trans-fatty-acids-on-insulin-resistance-and-type-2-diabetes
#11
Bénédicte L Tremblay, Iwona Rudkowska
Evidence from observational studies suggests beneficial effects of ruminant trans fatty acids (rTFA) on insulin resistance (IR) and type 2 diabetes (T2D). However, beneficial effects of rTFA are not always observed in cell, animal, and human studies. This narrative review presents potential mechanisms of action of rTFA using nutrigenomics and microRNA results in an integrative model. In addition, the review presents factors, including measures of IR and T2D, dose and duration of studies, as well as health status, ethnicity, and genotypes of subjects, that may help explain the heterogeneity in response to rTFA supplementation...
March 7, 2017: Nutrition Reviews
https://www.readbyqxmd.com/read/28340010/non-proteinuric-rather-than-proteinuric-renal-diseases-are-the-leading-cause-of-end-stage-kidney-disease
#12
Davide Bolignano, Carmine Zoccali
Proteinuria is a distinguishing feature in primary and secondary forms of chronic glomerulonephritis, which contribute to no more than the 20% of the end-stage kidney disease (ESKD) population. The contribution of non-proteinuric nephropathies to the global ESKD burden is still poorly focused and scarce research efforts are dedicated to the elucidation of risk factors and mechanistic pathways triggering ESKD in these diseases. We abstracted information on proteinuria in the main renal diseases other than glomerulonephritides that may evolve into ESKD...
March 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339909/il-17-and-cd40-ligand-synergistically-stimulate-the-chronicity-of-diabetic-nephropathy
#13
Huey-Liang Kuo, Chiu-Ching Huang, Tze-Yi Lin, Ching-Yuang Lin
Background.: Early stages of diabetic nephropathy (DN) are characterized by an influx of inflammatory cells. Interactions between infiltrating T cells and podocytes may play an important role in the ongoing inflammatory response and remodelling. The aim of this study was to explore the role of IL-17 and CD40 ligand (CD40L) in DN. Methods.: The study design involved a case series. Kidney biopsy samples of 69 patients with type 2 diabetes were assessed for the presence of CD4 +  IL-17 +  T cells...
March 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339674/family-history-of-systemic-lupus-erythematosus-and-risk-of-autoimmune-disease-nationwide-cohort-study-in-denmark-1977-2013
#14
Constance Jensina Ulff-Møller, Jacob Simonsen, Kirsten Ohm Kyvik, Søren Jacobsen, Morten Frisch
Objective.: To provide population-based estimates of relative risk of SLE and other autoimmune diseases (ADs) in relatives of SLE patients. Methods.: A cohort of 5 237 319 Danish residents identified through the Civil Registration System was coupled to their relatives through the parental link and followed for SLE and other ADs between 1977 and 2013 through linkage to the National Patient Register. Twin zygosity was established through the Danish Twin Registry. Hazard ratios (HRs) with 95% CIs were calculated using Cox proportional hazards regression analyses...
February 20, 2017: Rheumatology
https://www.readbyqxmd.com/read/28339006/substance-p-accelerates-wound-healing-in-type-2-diabetic-mice-through-endothelial-progenitor-cell-mobilization-and-yes-associated-protein-activation
#15
Jihyun Um, Jinyeong Yu, Ki-Sook Park
Wound healing is delayed in diabetes due to a number of factors, including impaired angiogenesis and poor dermal healing. The present study demonstrated that subcutaneous administration of substance P (SP) accelerates wound healing in db/db type 2 diabetic mice (db/db mice). SP injection (10 nM/kg, subcutaneously) enhanced angiogenesis, induced the mobilization of endothelial progenitor cells (EPCs) and increased the number of EPC‑colony forming units (EPC‑CFUs) in the bone marrow of db/db mice. Immunohistochemistry was performed to check the effects of SP on the cellular proliferation and the subcellular localization of Yes-associated protein (YAP) in the wound dermis...
March 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338987/gamma-glutamyltransferase-levels-prediabetes-and-type-2-diabetes-a-mendelian-randomization-study
#16
Jana Nano, Taulant Muka, Symen Ligthart, Albert Hofman, Sarwa Darwish Murad, Harry LA Janssen, Oscar H Franco, Abbas Dehghan
Background: High levels of serum gamma-glutamyltransferase (GGT) are associated with increased risk of prediabetes and type 2 diabetes in observational studies. It is unclear whether this relationship is causal, arises from residual confounding or is a consequence of reverse causation. Methods: We used data from a prospective population-based cohort study, compromising 8611 individuals without diabetes at baseline. Cox proportional hazard models were used to study the association between serum GGT levels and incident prediabetes and diabetes...
March 13, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28338900/exposure-to-the-chinese-famine-of-1959-61-in-early-life-and-long-term-health-conditions-a-systematic-review-and-meta-analysis
#17
Chihua Li, L H Lumey
Background: Most Chinese people over 55 years old today have experienced the Great Leap Forward Famine of 1959-61. Many reports suggested that the famine could have profound long-term health effects for exposed birth cohorts. A systematic review and meta-analysis was carried out to summarize reported famine effects on long-term health. Methods: Relevant reports were identified by searching PubMed, Embase, Chinese Wanfang Data and Chinese National Knowledge Infrastructure databases...
March 3, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28338878/risk-of-diabetes-after-hysterectomy-with-or-without-oophorectomy-in-postmenopausal-women
#18
Juhua Luo, JoAnn E Manson, Rachel Peragallo Urrutia, Michael Hendryx, Erin S LeBlanc, Karen L Margolis
The aim of this study was to determine the associations between hysterectomy, bilateral salpingo-oophorectomy (BSO), and incidence of diabetes in postmenopausal women participating in the Women's Health Initiative (WHI), a series of trials conducted in the United States, during the period 1993-1998. A total of 67,130 postmenopausal women aged 50-79 years were followed for a mean of 13.4 years. Among them, 7,430 cases of diabetes were diagnosed. Multivariable Cox proportional hazards models were used to assess the association between hysterectomy/oophorectomy status and diabetes incidence...
March 6, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28338608/impact-of-high-carbohydrate-diet-on-metabolic-parameters-in-patients-with-type-2-diabetes
#19
REVIEW
Chan-Hee Jung, Kyung Mook Choi
In patients with type 2 diabetes mellitus (T2DM), whether dietary carbohydrates have beneficial or detrimental effects on cardiometabolic risk factors has drawn attention. Although a high-carbohydrate (HC) diet and a low-carbohydrate (LC) diet have gained popularity for several decades, there is scarce review focusing on the effects of HC diet on glucose, lipids and body weight in patients with T2DM. In this review, we examined recently-published literature on the effects of HC diets on metabolic parameters in T2DM...
March 24, 2017: Nutrients
https://www.readbyqxmd.com/read/28338308/penile-alterations-at-early-stage-of-type-1-diabetes-in-rats
#20
Mingfang Tao, Cemal Tasdemir, Seda Tasdemir, Ali Shahabi, Guiming Liu
OBJECTIVE: Diabetes affects the erectile function significantly. However, the penile alterations in the early stage of diabetes in experimental animal models have not been well studied. We examined the changes of the penis and its main erectile components in diabetic rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into 2 groups: streptozotocin (STZ)-induced diabetics and age-matched controls. Three or nine weeks after diabetes induction, the penis was removed for immunohistochemical staining of smooth muscle and neuronal nitric oxide synthase (nNOS) in midshaft penile tissues...
March 24, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
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