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https://www.readbyqxmd.com/read/28214558/small-heterodimer-partner-shp-contributes-to-insulin-resistance-in-cardiomyocytes
#1
Ricardo Rodríguez-Calvo, Dipanjan Chanda, Yvonne Oligschlaeger, Marie Miglianico, Will A Coumans, Emma Barroso, Marta Tajes, Joost Jfp Luiken, Jan Fc Glatz, Manuel Vázquez-Carrera, Dietbert Neumann
Small heterodimer partner (SHP) is an atypical nuclear receptor expressed in heart that has been shown to inhibit the hypertrophic response. Here, we assessed the role of SHP in cardiac metabolism and inflammation. Mice fed a high-fat diet (HFD) displayed glucose intolerance accompanied by increased cardiac mRNA levels of Shp. In HL-1 cardiomyocytes, SHP overexpression inhibited both basal and insulin-stimulated glucose uptake and impaired the insulin signalling pathway (evidenced by reduced AKT and AS160 phosphorylation), similar to insulin resistant cells generated by high palmitate/high insulin treatment (HP/HI; 500μM/100nM)...
February 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213130/dipeptidyl-peptidase-4-impairs-insulin-signalling-and-promotes-lipid-accumulation-in-hepatocytes
#2
Kerstin Rufinatscha, Bernhard Radlinger, Jochen Dobner, Sabrina Folie, Claudia Bon, Elisabeth Profanter, Claudia Ress, Karin Salzmann, Gabriele Staudacher, Herbert Tilg, Susanne Kaser
Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signalling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively...
February 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28211608/preclinical-characterisation-of-55p0251-a-novel-compound-that-amplifies-glucose-stimulated-insulin-secretion-and-counteracts-hyperglycaemia-in-rodents
#3
Karin Stadlbauer, Barbara Brunmair, Zsuzsanna Lehner, Immanuel Adorjan, Thomas Scherer, Anton Luger, Leonhardt Bauer, Clemens Fürnsinn
AIMS: 55P0251 is a novel compound with blood glucose lowering activity in mice, which has been developed from a molecular backbone structure found in herbal remedies. We here report its basic pharmacological attributes and initial progress in unmasking the mode of action. MATERIALS AND METHODS: Pharmacokinetic properties of 55P0251 were portrayed in several species. First efforts to elucidate the glucose lowering mechanism in rodents included numerous experimental protocols dealing with glucose tolerance, insulin secretion from isolated pancreatic islets, and comparison to established drugs...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28211546/differential-effects-of-hormones-on-cellular-metabolism-in-keratoconus-in-vitro
#4
Tina B McKay, Jesper Hjortdal, Henrik Sejersen, Dimitrios Karamichos
Keratoconus (KC) is a corneal thinning disease with an onset commonly immediately post-puberty and stabilization by 40 to 50 years of age. The role of hormones in regulating corneal tissue structure in homeostatic and pathological conditions is unknown. Our group recently linked altered hormone levels to KC. Our current study sought to investigate and delineate the effects of exogenous hormones, such as androgen, luteotropin, and estrogen, on corneal stroma bioenergetics. We utilized our established 3D in vitro model to characterize the effects of DHEA, prolactin, 17β-estradiol on insulin-growth factor-1 and -2 (IGF-1, -2) signaling and metabolic function in primary corneal fibroblasts from healthy controls (HCFs) and KC patients (HKCs)...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28210866/cost-effectiveness-of-insulin-degludec-versus-insulin-glargine-in-adults-with-type-1-and-type-2-diabetes-mellitus
#5
Marc Evans, Barrie Chubb, Jens Gundgaard
INTRODUCTION: To estimate the cost-effectiveness of insulin degludec (IDeg) versus insulin glargine U100 (IGlar U100) and new-to-market basal insulin analogues in patients with diabetes in order to aid decision-making in a complex basal insulin market. METHODS: A simple, short-term model was used to evaluate the costs and effects of treatment with IDeg versus IGlar U100 over a 12-month period in patients with type 1 (T1DM) and type 2 diabetes (T2DM) from the perspective of the UK National Health Service...
February 16, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28207812/of-the-milk-sugars-galactose-but-not-prebiotic-galacto-oligosaccharide-improves-insulin-sensitivity-in-male-sprague-dawley-rats
#6
Priska Stahel, Julie J Kim, Changting Xiao, John P Cant
BACKGROUND: Consumption of dairy products reduces risk of type 2 diabetes. Milk proteins and fats exhibit anti-diabetic properties but milk sugars have been studied little in this context. Galactose from milk lactose is readily converted to glycogen in the liver but its effects on insulin sensitivity have not been assessed. Prebiotic oligosaccharides from milk alter gut microbiota and can thereby influence host metabolism. Our objective was to assess the effect on insulin sensitivity of dietary galactose compared to glucose and fructose, and fermentable galacto-oligosaccharides compared to non-fermentable methylcellulose...
2017: PloS One
https://www.readbyqxmd.com/read/28201828/add-on-exenatide-treatment-is-beneficial-in-poorly-controlled-obese-type-2-diabetics-under-intensive-insulin-regimens
#7
Alper Sönmez, Mustafa Dinç, Abdullah Taşlıpınar, Aydogan Aydoğdu, Coskun Meriç, Yalcin Başaran, Cem Haymana, Orhan Demir, İlker Yılmaz, Ömer Azal
Background: Intensive insulin treatment is bothersome in obese patients with type 2 diabetes mellitus. High insulin dosages further increase weight gain and the risk of hypoglycemia. Glucagon like peptide-1 receptor agonists decrease the insulin need, cause weight loss and reduce the risk of hypoglycemia. There is limited data about the effect of exenatide on obese diabetics under intensive insulin regimens. Methods: This retrospective case series report the clinical outcomes of 23 obese (13 morbidly obese) patients with uncontrolled type 2 diabetes mellitus (Age=59±10...
February 15, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28198575/tat-biliverdin-reductase-a-protects-ins-1-cells-from-human-islet-amyloid-polypeptide-induced-cytotoxicity-by-alleviating-oxidative-stress-and-er-stress
#8
Su Jin Lee, Hyung Kyung Kang, Won Sik Eum, Jinseu Park, Soo Young Choi, Hyeok Yil Kwon
Human islet amyloid polypeptide (hIAPP), a major constituent of islet amyloid deposits, induces pancreatic β-cell apoptosis and eventually contributes to β-cell deficit in patients with type 2 diabetes mellitus (T2DM). In this study, Tat-mediated transduction of biliverdin reductase A (BLVRA) was investigated in INS-1 cells to examine whether exogenous supplementation of BLVRA prevented hIAPP-induced apoptosis and dysfunction in insulin secretion in β-cells. Tat-BLVRA fusion protein was efficiently delivered into INS-1 cells in a time- and dose-dependent manner...
February 15, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28194805/fetal-adaptations-in-insulin-secretion-result-from-high-catecholamines-during-placental-insufficiency
#9
Sean W Limesand, Paul J Rozance
Placental insufficiency and intrauterine growth restriction (IUGR) of the fetus affects approximately 8% of all pregnancies and is associated with short- and long-term disturbances in metabolism. In pregnant sheep, experimental models with a small, defective placenta that restricts delivery of nutrients and oxygen to the fetus result in IUGR. Low blood oxygen concentrations increase fetal plasma catecholamine concentrations, which lower fetal insulin concentrations. All of these observations in sheep models with placental insufficiency are consistent with cases of human IUGR...
February 14, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28187863/a-review-of-the-clinical-efficacy-and-safety-of-insulin-degludec-and-glargine-300-u-ml-in-the-treatment-of-diabetes-mellitus
#10
REVIEW
Vincent C Woo
PURPOSE: The treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) using insulin is not ideal at this time. Despite advances made with basal insulin analogues, many individuals achieve less than optimal glycemic control or are at risk for hypoglycemia. Currently available basal insulin analogues do not deliver steady, peakless, continuous insulin for >24 hours and are associated with adverse events, including hypoglycemia. The objective of this paper was to review the clinical efficacy and safety of upcoming long-acting insulin analogues such as insulin degludec and insulin glargine 300 U/mL (Gla-300)...
February 7, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28187765/does-a-lack-of-physical-activity-explain-the-rheumatoid-arthritis-lipid-profile
#11
Hiba AbouAssi, Margery A Connelly, Lori A Bateman, K Noelle Tune, Janet L Huebner, Virginia B Kraus, Deborah A Winegar, James D Otvos, William E Kraus, Kim M Huffman
BACKGROUND: In rheumatoid arthritis (RA), cardiovascular risk is associated with paradoxical reductions in total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C). Concentrations of small LDL (LDL-P) and HDL (HDL-P) particles are also reduced with increased inflammation and disease activity in RA patients. Here we sought to identify which measure(s) of inflammation, disease activity and cardiometabolic risk contribute most to the RA-associated lipoprotein profile...
February 10, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28183563/effect-of-basal-insulin-dosage-on-blood-glucose-concentration-in-ambulatory-surgery-patients-with-type-2-diabetes
#12
Linda J Demma, Karen T Carlson, Elizabeth W Duggan, John Gordon Morrow, Guillermo Umpierrez
STUDY OBJECTIVE: Among patients with type 2 diabetes treated with insulin, perioperative hyperglycemia and hypoglycemia may cause undesirable symptoms, surgery delay or cancellation, or unexpected hospitalization. Our objective was to compare preoperative glargine dosing regimens on perioperative glycemic control in patients undergoing ambulatory surgery. DESIGN: Observational study. SETTING: Pre- and postoperative holding areas. PATIENTS: One hundred fifty patients with type 2 diabetes using a once daily, evening insulin glargine regimen undergoing ambulatory surgery were included...
February 2017: Journal of Clinical Anesthesia
https://www.readbyqxmd.com/read/28183452/controversies-in-the-management-of-hyperglycaemic-emergencies-in-adults-with-diabetes
#13
REVIEW
Luís Cardoso, Nuno Vicente, Dírcea Rodrigues, Leonor Gomes, Francisco Carrilho
Hyperglycaemic emergencies are associated with significant morbi-mortality and healthcare costs. Management consists on fluid replacement, insulin therapy, and electrolyte correction. However, some areas of patient management remain debatable. In patients without respiratory failure or haemodynamic instability, arterial and venous pH and bicarbonate measurements are comparable. Fluid choice varies upon replenishment phase and patient's condition. If patient is severely hypovolaemic, normal saline solution should be the first option...
March 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28179966/efficacy-and-safety-of-vildagliptin-as-an-add-on-therapy-in-inadequately-controlled-type-2-diabetes-patients-treated-with-basal-insulin
#14
Daisuke Saito, Akio Kanazawa, Nayumi Shigihara, Fumihiko Sato, Toyoyoshi Uchida, Junko Sato, Hiromasa Goto, Takeshi Miyatsuka, Fuki Ikeda, Takeshi Ogihara, Chie Ohmura, Hirotaka Watada
BACKGROUND: The aim of this study was to investigate the efficacy and safety of vildagliptin as an add-on therapy for patients with type 2 diabetes mellitus inadequately controlled with basal insulin. METHODS: Twenty-four patients treated with basal insulin and oral anti-diabetes drugs were randomly allocated into two groups: the control group (did not receive any add-on drugs) and vildagliptin group (received vildagliptin 100 mg/day for 6 months). The primary outcome was changes in hemoglobin A1c (HbA1c) from baseline to end of study...
March 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28176957/determinants-of-weight-change-in-patients-on-basal-insulin-treatment-an-analysis-of-the-dive-registry
#15
Peter Bramlage, Tobias Bluhmki, Holger Fleischmann, Matthias Kaltheuner, Jan Beyersmann, Reinhard W Holl, Thomas Danne
OBJECTIVE: We aimed to describe patterns of weight change in insulin-naive patients with type 2 diabetes mellitus (T2DM) starting basal insulin (BI) treatment. RESEARCH DESIGN AND METHODS: Diabetes Versorgungs-Evaluation (DIVE) is an observational, multicenter, prospective registry in patients with T2DM. Patients were divided into those initiating BI therapy for the first time (with optional oral antidiabetic drugs (OADs)) and those initiating OADs only (OADo). RESULTS: 521 patients were included in the analysis, 113 in the BI arm and 408 in the OADo arm...
2017: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/28176886/assessment-of-channeling-bias-among-initiators-of-glucose-lowering-drugs-a-uk-cohort-study
#16
Mikkel Z Ankarfeldt, Brian L Thorsted, Rolf Hh Groenwold, Erpur Adalsteinsson, M Sanni Ali, Olaf H Klungel
BACKGROUND: Channeling bias may occur when a newly marketed drug and an established drug, despite similar indications, are prescribed to patients with different prognostic characteristics (ie, confounding). AIM: To investigate channeling bias and its impact on relative effectiveness of glucagon-like peptide-1 (GLP-1) analogs versus basal insulin and dipeptidyl peptidase-4 inhibitors (DPP-4i) versus sulfonylurea. METHODS: In the UK Clinical Practice Research Datalink, patients with type 2 diabetes initiating treatment between 2006 and 2015 were included...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28169086/basal-insulin-treatment-intensification-in-patients-with-type-2-diabetes-mellitus-a-comprehensive-systematic-review-of-current-options
#17
REVIEW
D Raccah
AIM: As type 2 diabetes mellitus progresses, most patients require treatment with basal insulin in combination with another agent to achieve recommended glycaemic targets. The purpose of this systematic review was to examine the evidence supporting the use of the available add-on treatments [rapid-acting insulin (RAI), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors] to basal insulin...
February 3, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28168767/lifestyle-change-reduces-cardiometabolic-risk-factors-and-glucagon-like-peptide-1-levels-in-obese-first-degree-relatives-of-people-with-diabetes
#18
A Bowes, J Begley, D Kerr
BACKGROUND: Preventing type 2 diabetes in a real-world setting remains challenging. The present study aimed to assess the effectiveness of a lifestyle-based programme for individuals at high risk of developing type 2 diabetes as assessed by achieved weight loss, cardiovascular risk factors and glucagon-like peptide-1 (GLP-1). METHODS: Sixty-six obese individuals with history of diabetes in first-degree relatives participated in an 8-month lifestyle programme consisting of 12 × 1...
February 7, 2017: Journal of Human Nutrition and Dietetics: the Official Journal of the British Dietetic Association
https://www.readbyqxmd.com/read/28168232/radiographic-basal-ganglia-abnormalities-secondary-to-nonketotic-hyperglycemia-with-unusual-clinical-features
#19
Ju Young Choi, Joon Min Park, Kyung Hwan Kim, Jun Seok Park, Dong Wun Shin, Hoon Kim, Woo Chan Jeon, Hyun Jong Kim
A 77-year-old woman was admitted to a local clinic for altered consciousness and presented with a suspected basal ganglion hemorrhage detected on brain computed tomography. The patient was stuporous, but her vital signs were stable. Her initial blood glucose was 607 mg/dL, and a hyperdense lesion was found in the right basal ganglion on brain computed tomography. T1-weighted magnetic resonance imaging revealed high signal intensity in the right basal ganglion. Electroencephalography showed no seizure activity...
December 2016: Clinical and Experimental Emergency Medicine
https://www.readbyqxmd.com/read/28164072/leptin-and-adiponectin-levels-in-girls-with-central-precocious-puberty-before-and-during-gnrh-agonist-treatment
#20
Jae Won Yoo, Chun Woo Song, Han Hyuk Lim
PURPOSE: The effects of gonadotropin-releasing hormone agonist (GnRHa) treatment on the energy metabolism in girls with central precocious puberty (CPP) are controversial. We focused the changes and related factors of serum levels of leptin and adiponectin in girls with CPP before and during GnRHa treatment. METHODS: Thirty girls with idiopathic CPP were enrolled in the study. Their auxological data and fasting blood were collected at the baseline and after six months of GnRHa treatment...
December 2016: Annals of Pediatric Endocrinology & Metabolism
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