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Diabetes therapy

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https://www.readbyqxmd.com/read/28340340/selective-chemical-inhibition-of-pgc-1%C3%AE-gluconeogenic-activity-ameliorates-type-2-diabetes
#1
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/28339838/the-clinical-epidemiology-of-young-adults-starting-renal-replacement-therapy-in-the-uk-presentation-management-and-survival-using-15-years-of-uk-renal-registry-data
#2
Alexander J Hamilton, Anna Casula, Yoav Ben-Shlomo, Fergus J Caskey, Carol D Inward
Background: Clinical epidemiology data for young adults on renal replacement therapy (RRT) are lacking. While mostly transplanted, they have an increased risk of graft loss during young adulthood. Methods: We combined the UK Renal Registry paediatric and adult databases to describe patient characteristics, transplantation and survival for young adults. We grouped patients 11-30 years of age starting RRT from 1999 to 2008 by age band and examined their course during 5 years of follow-up...
February 23, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28335557/ros-production-and-erk-activity-are-involved-in-the-effects-of-d-%C3%AE-hydroxybutyrate-and-metformin-in-a-glucose-deficient-condition
#3
Santosh Lamichhane, Tonking Bastola, Ramesh Pariyar, Eun-Sol Lee, Ho-Sub Lee, Dae Ho Lee, Jungwon Seo
Hypoglycemia, a complication of insulin or sulfonylurea therapy in diabetic patients, leads to brain damage. Furthermore, glucose replenishment following hypoglycemic coma induces neuronal cell death. In this study, we investigated the molecular mechanism underlying glucose deficiency-induced cytotoxicity and the protective effect of d-β-hydroxybutyrate (D-BHB) using SH-SY5Y cells. The cytotoxic mechanism of metformin under glucose deficiency was also examined. Cell viability under 1 mM glucose (glucose deficiency) was significantly decreased which was accompanied by increased production of reactive oxygen species (ROS) and decreased phosphorylation of extracellular signal-regulated kinase (ERK) and glycogen synthase 3 (GSK3β)...
March 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28335529/effects-of-momordica-charantia-bitter-melon-on-ischemic-diabetic-myocardium
#4
Attila Czompa, Alexandra Gyongyosi, Kitti Szoke, Istvan Bak, Evelin Csepanyi, David D Haines, Arpad Tosaki, Istvan Lekli
Objective: A rat model is here used to test a hypothesis that Momordica charantia (Bitter melon (BM)) extract favorably alters processes in cardiovascular tissue and is systemically relevant to the pathophysiology of type 2 diabetes (T2DM) and related cardiovascular disease. Methods: Male Lean and Zucker Obese (ZO) rats were gavage-treated for six weeks with 400 mg/kg body weight bitter melon (BM) extract suspended in mucin-water vehicle, or with vehicle (Control). Animals were segregated into four treatment groups, 10 animals in each group, according to strain (Lean or ZO) and treatment (Control or BM)...
March 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28334746/a-newborn-with-transient-diabetes-mellitus-accompanied-by-ketoacidosis-attributable-to-a-zfp57-mutation
#5
Fatma Iyigun, Beyza Ozcan, Ferit Kulali, Istemi Han Celik, Semra Cetinkaya, Ahmet Yagmur Bas, Nihal Demirel
Hyperglycemia commencing within the first 6 months of life requires exogenous insulin therapy and, if the condition persists for >2 weeks, is termed neonatal diabetes mellitus (NDM). This rare illness is of two types: transient and permanent NDM. Most cases come to medical attention because of nonspecific symptoms, including intrauterine growth retardation, dehydration, difficulties in feeding and inadequate weight gain. In the present article, we describe an infant who smelt of ketones during examination and who was diagnosed with transient NDM caused by a ZFP57 mutation, accompanied by ketoacidosis...
February 18, 2017: Journal of Tropical Pediatrics
https://www.readbyqxmd.com/read/28334683/combined-metformin-and-insulin-treatment-reverses-metabolically-impaired-omental-adipogenesis-and-accumulation-of-4-hydroxynonenal-in-obese-diabetic-patients
#6
Morana Jaganjac, Shamma Almuraikhy, Fatima Al-Khelaifi, Mashael Al-Jaber, Moataz Bashah, Nayef A Mazloum, Kamelija Zarkovic, Neven Zarkovic, Georg Waeg, Wael Kafienah, Mohamed A Elrayess
OBJECTIVE: Obesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). This study investigated whether impaired adipogenesis of omental (OM) adipose tissues and elevated 4-hydroxynonenal (4-HNE) accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype. METHODS: OM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery...
March 16, 2017: Redox Biology
https://www.readbyqxmd.com/read/28334605/new-horizons-in-diabetic-neuropathy-mechanisms-bioenergetics-and-pain
#7
REVIEW
Eva L Feldman, Klaus-Armin Nave, Troels S Jensen, David L H Bennett
Pre-diabetes and diabetes are a global epidemic, and the associated neuropathic complications create a substantial burden on both the afflicted patients and society as a whole. Given the enormity of the problem and the lack of effective therapies, there is a pressing need to understand the mechanisms underlying diabetic neuropathy (DN). In this review, we present the structural components of the peripheral nervous system that underlie its susceptibility to metabolic insults and then discuss the pathways that contribute to peripheral nerve injury in DN...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28334539/-long-acting-insulins-in-the-treatment-of-type-2%C3%A2-diabetes-and-their-position-in-the-current-treatment-algorithm
#8
Martin Haluzík
Insulin therapy has been for many years an inseparable part of the treatment of patients with type 2 diabetes, in particular those with longer diabetes duration. Current national and international guidelines list insulin treatment as a possible second choice therapy in patient with unsatisfactory glucose control on monotherapy with metformin. In reality, insulin therapy is often initiated later than it optimally should be. The reasons include among others the fear of patients and sometimes also of physicians from the side effects of insulin...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28333387/pathophysiological-fundamentals-of-diabetic-cardiomyopathy
#9
Xinyue Hu, Tao Bai, Zheng Xu, Qiuju Liu, Yang Zheng, Lu Cai
Diabetic cardiomyopathy (DCM) was first recognized more than four decades ago and occurred independent of cardiovascular diseases or hypertension in both type 1 and type 2 diabetic patients. The exact mechanisms underlying this disease remain incompletely understood. Several pathophysiological bases responsible for DCM have been proposed, including the presence of hyperglycemia, nonenzymatic glycosylation of large molecules (e.g., proteins), energy metabolic disturbance, mitochondrial damage and dysfunction, impaired calcium handling, reactive oxygen species formation, inflammation, cardiac cell death, and cardiac hypertrophy and fibrosis, leading to impairment of cardiac contractile functions...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333071/combined-effects-of-curcumin-and-lycopene-or-bixin-in-yoghurt-on-inhibition-of-ldl-oxidation-and-increases-in-hdl-and-paraoxonase-levels-in-streptozotocin-diabetic-rats
#10
Renata Pires Assis, Carlos Alberto Arcaro, Vânia Ortega Gutierres, Juliana Oriel Oliveira, Paulo Inácio Costa, Amanda Martins Baviera, Iguatemy Lourenço Brunetti
Combination therapy using natural antioxidants to manage diabetes mellitus and its complications is an emerging trend. The aim of this study was to investigate the changes promoted by treatment of streptozotocin (STZ)-diabetic rats with yoghurt enriched with the bioactives curcumin, lycopene, or bixin (the latter two being carotenoids). Antioxidants were administered individually, or as mixtures, and biomarkers of metabolic and oxidative disturbances, particularly those associated with cardiovascular risk, were assessed...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28332871/sodium-glucose-cotransporter-2-and-dipeptidyl-peptidase-4-inhibition-promise-of-a-dynamic-duo
#11
Ildiko Lingvay
OBJECTIVE: This article reviews evidence supporting sodium glucose cotransporter 2 (SGLT2) inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor combination therapy for management of type 2 diabetes mellitus (T2DM). METHODS: We conducted a non-systematic review of the literature focusing on single-pill or fixed-dose combinations of SGLT2 inhibitors and DPP-4 inhibitors available in the United States. RESULTS: SGLT2 inhibitors and DPP-4 inhibitors have complementary mechanisms of action that address several of the underlying pathophysiological abnormalities present in T2DM without overlapping toxicities...
March 23, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28332143/the-relationship-between-increases-in-morning-spot-urinary-glucose-excretion-and-decreases-in-hba1c-in-patients-with-type-2-diabetes-after-taking-an-sglt2-inhibitor-a-retrospective-longitudinal-study
#12
So Ra Kim, Yong-Ho Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee
INTRODUCTION: Sodium glucose co-transporter 2 (SGLT2) inhibitors increase urinary glucose excretion (UGE) by reducing the renal threshold for glucose excretion, which results in decreased serum glucose concentrations in patients with type 2 diabetes mellitus (T2D). However, no study to date has determined whether larger increases in UGE after SGLT2 inhibitor treatment correspond to larger reductions in glycated hemoglobin (HbA1C). METHODS: We enrolled participants who were newly prescribed an SGLT2 inhibitor (dapagliflozin 10 mg or ipragliflozin 50 mg, once daily) as an add-on therapy...
March 22, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28332067/preoperative-chronic-sinusitis-as-significant-cause-of-postoperative-infection-and-implant-loss-after-sinus-augmentation-from-a-lateral-approach
#13
Ayako Kozuma, Masanori Sasaki, Katsuhiro Seki, Takeshi Toyoshima, Hiroyuki Nakano, Yoshihide Mori
OBJECTIVES: Among intra/postoperative complications of sinus augmentation from a lateral approach, postoperative infection and implant loss are particularly important because they have irreversible consequences. The purpose of this study was to determine the causes of postoperative infection and implant loss after a lateral approach and to determine the appropriate prophylaxis and therapy. MATERIALS AND METHODS: In total, 109 patients (121 sinuses, 252 implants) were included in this study...
March 22, 2017: Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28331986/renal-function-preservation-with-pioglitazone-or-with-basal-insulin-as-an-add-on-therapy-for-patients-with-type-2-diabetes-mellitus
#14
Yu-Hung Chang, Der-Wei Hwu, Dao-Ming Chang, Ling-Wang An, Chang-Hsun Hsieh, Yau-Jiunn Lee
AIMS: Clinical outcome may differ owing to the distinct pharmacological characteristics of insulin sensitizers and insulin. This study was performed to compare the metabolic and renal function changes with add-on pioglitazone treatment versus basal insulin in patients with type 2 diabetes mellitus (DM) in whom sulfonylurea and metformin regimens failed. METHODS: Patients who were consecutively managed in the diabetes comprehensive program with add-on pioglitazone or detemir/glargine treatment for at least 2 years following sulfonylurea and metformin treatment failure were included...
March 22, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28331855/diabetes-in-hfe-hemochromatosis
#15
REVIEW
James C Barton, Ronald T Acton
Diabetes in whites of European descent with hemochromatosis was first attributed to pancreatic siderosis. Later observations revealed that the pathogenesis of diabetes in HFE hemochromatosis is multifactorial and its clinical manifestations are heterogeneous. Increased type 2 diabetes risk in HFE hemochromatosis is associated with one or more factors, including abnormal iron homeostasis and iron overload, decreased insulin secretion, cirrhosis, diabetes in first-degree relatives, increased body mass index, insulin resistance, and metabolic syndrome...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28331372/a-glucokinase-gene-mutation-in-a-young-boy-with-diabetes-mellitus-hyperinsulinemia-and-insulin-resistance
#16
Andrey O Emelyanov, Elena Sechko, Ekaterina Koksharova, Igor Sklyanik, Tamara Kuraeva, Alexander Mayorov, Valentina Peterkova, Ivan Dedov
We report the case of a 12-year-old boy with a glucokinase (GCK) mutation, and diabetes with hyperinsulinemia and insulin resistance. For 4 years, the patient intermittently received insulin medications Actrapid HM and Protaphane HM (total dose 5 U/day), with glycated hemoglobin (HbA1c) levels of 6.6%-7.0%. After extensive screening the patient was found to carry a heterozygous mutation (p.E256K) in GCK (MIM #138079, reference sequence NM_000162.3). Insulin therapy was replaced by metformin at 1,700 mg/day...
2017: International Medical Case Reports Journal
https://www.readbyqxmd.com/read/28331365/mastectomy-skin-flap-necrosis-challenges-and-solutions
#17
REVIEW
Stuart A Robertson, Johann A Jeevaratnam, Avi Agrawal, Ramsey I Cutress
INTRODUCTION: Mastectomy skin flap necrosis (MSFN) has a reported incidence of 5%-30% in the literature. It is often a significant and underappreciated problem. The aim of this article was to review the associated challenges and possible solutions. METHODS: A MEDLINE search was performed using the search term "mastectomy skin flap necrosis". Titles and abstracts from peer-reviewed publications were screened for relevance. RESULTS: MSFN is a common complication and may present as partial- or full-thickness necrosis...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28331351/long-term-management-of-type-2-diabetes-with-glucagon-like-peptide-1-receptor-agonists
#18
REVIEW
Hamish Courtney, Rahul Nayar, Chinnadorai Rajeswaran, Ravi Jandhyala
Continuously reducing excess blood glucose is a primary goal for the management of type 2 diabetes (T2D). Most patients with T2D require glucose-lowering medications to achieve and maintain adequate glycemic control; however, treatment failure may occur, limiting treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an emerging therapeutic class that can be prescribed for patients instead of basal insulin after the failure of oral therapies. Recent studies have focused on the durability and tolerability of long-term GLP-1RA therapy...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28331117/comparison-between-effectiveness-of-100-mg-day-sitagliptin-and-a-switch-to-mitiglinide-calcium-hydrate-voglibose-from-50-mg-day-sitagliptin-in-patients-with-type-2-diabetes
#19
Tadashi Arao, Yosuke Okada, Keiichi Torimoto, Kei Sugai, Takashi Otsuka, Akira Kurozumi, Yoshiya Tanaka
We analyzed the effects of 100 mg/day sitagliptin and a switch to mitiglinide calcium hydrate/voglibose compound tablets (MIT/VOG) in patients with type 2 diabetes mellitus (T2DM) treated with 50 mg/day sitagliptin. Five patients with T2DM treated with 50 mg/day sitagliptin and hemoglobin A1c (HbA1c) of ≥6.5% were switched to MIT/VOG, or the dose of sitagliptin was increased to 100 mg/day. The effects of the changes in therapy were compared in a crossover fashion by continuous glucose monitoring. The primary endpoint was mean amplitude of glycemic excursions (MAGE), and the secondary end points were 24-hour mean blood glucose level and mean blood glucose level from 0:00 a...
2017: Journal of UOEH
https://www.readbyqxmd.com/read/28330905/secretogranin-iii-as-a-disease-associated-ligand-for-antiangiogenic-therapy-of-diabetic-retinopathy
#20
Michelle E LeBlanc, Weiwen Wang, Xiuping Chen, Nora B Caberoy, Feiye Guo, Chen Shen, Yanli Ji, Hong Tian, Hui Wang, Rui Chen, Wei Li
Diabetic retinopathy (DR) is a leading cause of vision loss with retinal vascular leakage and/or neovascularization. Current antiangiogenic therapy against vascular endothelial growth factor (VEGF) has limited efficacy. In this study, we applied a new technology of comparative ligandomics to diabetic and control mice for the differential mapping of disease-related endothelial ligands. Secretogranin III (Scg3) was discovered as a novel disease-associated ligand with selective binding and angiogenic activity in diabetic but not healthy vessels...
March 22, 2017: Journal of Experimental Medicine
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