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Insulin tolerance

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https://www.readbyqxmd.com/read/28727908/leveraging-a-clinical-phase-ib-proof-of-concept-study-for-the-gpr40-agonist-mk-8666-in-patients-with-type-2-diabetes-for-model-informed-phase-ii-dose-selection
#1
A W Krug, P Vaddady, R A Railkar, B J Musser, J Cote, Agh Ederveen, D G Krefetz, E DeNoia, A L Free, L Morrow, M V Chakravarthy, E Kauh, D A Tatosian, P A Kothare
GPR40 mediates free fatty acid-induced insulin secretion in beta cells. We investigated the safety, pharmacokinetics, and glucose response of MK-8666, a partial GPR40 agonist, after once-daily multiple dosing in type 2 diabetes patients. This double-blind, multisite, parallel-group study randomized 63 patients (placebo, n = 18; 50 mg, n = 9; 150 mg, n = 18; 500 mg, n = 18) for 14-day treatment. The results showed no serious adverse effects or treatment-related hypoglycemia. One patient (150-mg group) showed mild-to-moderate transaminitis at the end of dosing...
July 20, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28727165/increased-fibre-and-reduced-trans-fatty-acid-intake-are-primary-predictors-of-metabolic-improvement-in-overweight-polycystic-ovary-syndrome-substudy-of-randomized-trial-between-diet-exercise-and-diet-plus-exercise-for-weight-control
#2
Åsa Nybacka, Per M Hellström, Angelica L Hirschberg
OBJECTIVE: Polycystic ovary syndrome (PCOS) is commonly affected by obesity. PCOS phenotypes are prone to increased waist/hip ratio, insulin resistance and dyslipidaemia. This substudy was undertaken to evaluate the effects of lifestyle interventions on metabolic biomarkers in overweight/obese PCOS women, and the interventional effects of dietary components related to metabolic outcomes. DESIGN: Randomized three-arm parallel study. PATIENTS: Fifty-seven PCOS women (BMI >27kg/m(2) , age 18-40) were randomly assigned to diet (D, n=19), exercise (E, n=19) or diet plus exercise (DE, n=19) in three-arm fashion over 16 weeks...
July 20, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28726334/insulin-sensitivity-across-the-lifespan-from-obese-adolescents-to-obese-adults-with-impaired-glucose-tolerance-who-is-worse-off
#3
Silva Arslanian, Joon Young Kim, Alexis Nasr, Fida Bacha, Hala Tfayli, SoJung Lee, Frederico G S Toledo
OBJECTIVE: Youth type 2 diabetes mellitus (T2DM) occurs decades earlier than adult T2DM and is characterized by high therapeutic failure rates and decreased response to insulin sensitizers suggesting a more severe disease process than in adults. To explain these observations, we hypothesized that insulin resistance is worse in obese youth than adults with impaired glucose tolerance (IGT), a state of high-risk for T2DM. As proof-of-concept, we compared insulin sensitivity between BMI-, sex-, and race-matched obese youth vs adults with IGT...
July 20, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28726200/intranasal-insulin-restores-metabolic-parameters-and-insulin-sensitivity-in-rats-with-metabolic-syndrome
#4
K V Derkach, A O Ivantsov, O V Chistyakova, I B Sukhov, D M Buzanakov, A A Kulikova, A O Shpakov
We studied the effect of 10-week treatment with intranasal insulin (0.5 IU/day) on glucose tolerance, glucose utilization, lipid metabolism, functions of pancreatic β cells, and insulin system in the liver of rats with cafeteria diet-induced metabolic syndrome. The therapy reduced body weight and blood levels of insulin, triglycerides, and atherogenic cholesterol that are typically increased in metabolic syndrome, normalized glucose tolerance and its utilization, and increased activity of insulin signaling system in the liver, thus reducing insulin resistance...
July 18, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28725316/post-prandial-plasma-glucose-less-than-or-equal-to-70-mg-dl-is-not-uncommon-in-young-japanese-women
#5
Ayaka Tsuboi, Mika Takeuchi, Kaori Kitaoka, Satomi Minato, Miki Kurata, Tsutomu Kazumi, Keisuke Fukuo
BACKGROUND: Post-breakfast/post-challenge plasma glucose (PG) concentrations were studied less in young normal weight Japanese women. We addressed these issues. METHODS: Two separate groups of female collegiate athletes and female untrained students underwent either a standardized meal test or a standard 75-g oral glucose tolerance test, but not both. Frequency of women whose post-breakfast/post-load PG fell to 70 mg/dL or lower (termed as low glycemia) was compared between athletes and non-athletes, who also underwent measurements of serum adipokines, markers of insulin resistance and inflammation and dual-energy X-ray absorptiometry...
August 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28725256/the-effect-of-high-intensity-breastfeeding-on-postpartum-glucose-tolerance-in-women-with-recent-gestational-diabetes
#6
Ichiro Yasuhi, Tomoko Soda, Hiroshi Yamashita, Atsuko Urakawa, Mihoko Izumi, Yukari Kugishima, Yasushi Umezaki
BACKGROUND: Although breastfeeding is expected to reduce the incidence of diabetes in women with gestational diabetes, the effect has not been clearly confirmed. We examined whether or not high-intensity breastfeeding reduces the incidence of abnormal glucose tolerance and investigated the effect of high-intensity breastfeeding on insulin resistance during the first year postpartum in Japanese women with current gestational diabetes. METHODS: In this retrospective study, we included women with gestational diabetes who underwent postpartum 75 g oral glucose tolerance test during the first year (12-14 months) postpartum from 2009 to 2011 at a single tertiary perinatal care center in Japan...
2017: International Breastfeeding Journal
https://www.readbyqxmd.com/read/28724270/synergistic-effects-of-ad-libitum-low-dose-fructose-drinking-and-low-dose-streptozotocin-treatment-in-wistar-rats-a-mild-model-of-type-2-diabetes
#7
Asie Sadeghi, Maani Beigy, Samira Alizadeh, Hossein Mazloom, Sanaz Vakili, Saideh Ahmadi, Reza Meshkani
To develop a convenient animal model of T2D by pretreatment with low-dose 10% w/v fructose (FRC) solution followed by the injection of low doses of streptozotocin (STZ) in Wistar rats. For this 8-week experimental study; rats were first fed a standard chow ad-libitum diet and either tap water (n=40) or 10% w/v FRC solution (n=40) for 4 weeks. Next, rats in each category were randomly allocated to 4 subgroups (n=10 each) of low-dose STZ (25,35, and 45 mg/kg). The final mean fasting blood sugar (FBG) of FRC+STZ45 (197±55...
May 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/28724177/natural-molecules-for-the-therapy-of-hyperandrogenism-and-metabolic-disorders-in-pcos
#8
V Cappelli, M C Musacchio, A Bulfoni, G Morgante, V De Leo
OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of women of reproductive age and a complex endocrine condition, due to its heterogeneity and uncertainty about its etiology. However, PCOS is also associated with other metabolic abnormalities such as insulin resistance, impaired glucose tolerance, and diabetes. There are few medications that are approved for the most common symptoms of PCOS, leading to the off-label use of medications that were approved for other indications...
June 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28724056/prevalence-of-pancreatic-autoantibodies-in-non-diabetic-patients-with-autoimmune-thyroid-disease-and-its-relation-to-insulin-secretion-and-glucose-tolerance
#9
Carolina Sallorenzo, Regina Silva, Teresa Kasamatsu, Sérgio Dib
Objective: We evaluated the prevalence of glutamic acid decarboxylase (GADA) and tyrosine phosphatase-protein antibodies (IA2A), their titers and their relation to first phase insulin response (FPIR) and glucose tolerance in autoimmune thyroid diseases (ATDs) patients. Subjects and methods: Graves' disease (GD; n = 181) and Hashimoto's thyroiditis (HT; n = 143) patients in addition to healthy controls (n = 93) were studied. Secondly, FPIR and oral glucose tolerance tests (OGTT) were performed in 11 anti-pancreatic islet-cell (+) and in 20 anti-pancreatic-cell (-) patients...
July 13, 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28723844/associations-of-physical-activity-intensities-with-markers-of-insulin-sensitivity
#10
Charlotte Jelleyman, Charlotte L Edwardson, Joseph Henson, Laura J Gray, Alex V Rowlands, Kamlesh Khunti, Melanie J Davies, Thomas Yates
BACKGROUND: Objectively measured physical activity (PA) intensity has traditionally been categorised as light, moderate and vigorous using laboratory calibrated cut-points. The relative contribution of time spent across a spectrum of accelerometer-determined intensities on health outcomes is less clear. PURPOSE: To assess the relationship between objectively measured PA intensity on a continuous scale and markers of insulin sensitivity. METHODS: Participants at high risk of type 2 diabetes were recruited from primary care (Leicestershire, UK)...
July 19, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28722653/directing-visceral-white-adipocyte-precursors-to-a-thermogenic-adipocyte-fate-improves-insulin-sensitivity-in-obese-mice
#11
Chelsea Hepler, Mengle Shao, Jonathan Y Xia, Alexandra L Ghaben, Mackenzie J Pearson, Lavanya Vishvanath, Ankit X Sharma, Thomas S Morley, William L Holland, Rana K Gupta
Visceral adiposity confers significant risk for developing metabolic disease in obesity whereas preferential expansion of subcutaneous white adipose tissue (WAT) appears protective. Unlike subcutaneous WAT, visceral WAT is resistant to adopting a protective thermogenic phenotype characterized by the accumulation of Ucp1(+) beige/BRITE adipocytes (termed "browning"). In this study, we investigated the physiological consequences of browning murine visceral WAT by selective genetic ablation of Zfp423, a transcriptional suppressor of the adipocyte thermogenic program...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28722106/anti-inflammatory-effects-of-exercise-role-in-diabetes-and-cardiovascular-disease
#12
REVIEW
Bente Klarlund Pedersen
BACKGROUND: Persistent inflammation is involved in the pathogenesis of chronic diseases such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). AIMS: The aim of this review was to provide the reader with an update of the mechanisms whereby exercise-induced cytokines may impact cardiometabolic diseases. RESULTS: Evidence exists that interleukin (IL)-1β is involved in pancreatic β-cell damage, whereas TNF-α is a key molecule in peripheral insulin resistance...
July 19, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28721439/effects-of-insulin-and-exercise-training-on-fgf21-its-receptors-and-target-genes-in-obesity-and-type-2-diabetes
#13
Rikke Kruse, Sara G Vienberg, Birgitte F Vind, Birgitte Andersen, Kurt Højlund
AIMS/HYPOTHESIS: Pharmacological doses of FGF21 improve glucose tolerance, lipid metabolism and energy expenditure in rodents. Induced expression and secretion of FGF21 from muscle may increase browning of white adipose tissue (WAT) in a myokine-like manner. Recent studies have reported that insulin and exercise increase FGF21 in plasma. Obesity and type 2 diabetes are potentially FGF21-resistant states, but to what extent FGF21 responses to insulin and exercise training are preserved, and whether FGF21, its receptors and target genes are altered, remains to be established...
July 18, 2017: Diabetologia
https://www.readbyqxmd.com/read/28721221/pasireotide-successful-treatment-of-a-sparsely-granulated-tumour-in-a-resistant-case-of-acromegaly
#14
W K M G Amarawardena, K D Liyanarachchi, J D C Newell-Price, R J M Ross, D Iacovazzo, M Debono
The granulation pattern of somatotroph adenomas is well known to be associated with differing clinical and biochemical characteristics, and it has been shown that sparsely granulated tumours respond poorly to commonly used somatostatin receptor ligands (SRLs). We report a challenging case of acromegaly with a sparsely granulated tumour resistant to multiple modalities of treatment, ultimately achieving biochemical control with pasireotide. A 26-year-old lady presented with classical features of acromegaly, which was confirmed by an oral glucose tolerance test...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28721138/the-effect-of-orlistat-versus-metformin-on-body-composition-and-insulin-resistance-in-obese-premenopausal-women-3-month-randomized-prospective-open-label-study
#15
Magdalena Kujawska-Łuczak, Katarzyna Musialik, Monika Szulińska, Ewelina Swora-Cwynar, Angelina Kargulewicz, Małgorzata Grzymisławska, Danuta Pupek-Musialik, Paweł Bogdański
INTRODUCTION: Our aim was to evaluate the effects of metformin and orlistat on body composition and glucose-insulin homeostasis in obese premenopausal women. MATERIAL AND METHODS: Seventy-three obese premenopausal Caucasian women aged 32.4 ±8.3 years were treated with either metformin (1000 mg/day; n = 37) or orlistat (360 mg/day; n = 36). Anthropometric parameters were measured using dual-energy X-ray absorptiometry. Glucose tolerance, using the oral glucose tolerance test; insulin resistance, using the homeostasis model assessment (HOMA-IR); and insulin sensitivity, using the Matsuda insulin sensitivity index (ISI Matsuda), were assessed at the commencement of the study and after 3 months...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28721067/phase-i-dose-escalation-study-of-long-acting-pasireotide-in-patients-with-neuroendocrine-tumors
#16
James C Yao, Jennifer A Chan, Alain C Mita, Madan G Kundu, Karina Hermosillo Reséndiz, Ke Hu, Shoba Ravichandran, Jonathan R Strosberg, Edward M Wolin
This phase I study aimed at determining the maximum tolerated dose (MTD) and characterizing the safety, tolerability, pharmacokinetics (PKs), and efficacy of pasireotide in patients with advanced neuroendocrine tumors (NETs). Patients were enrolled in two phases: dose-escalation phase (to determine the MTD) at a starting dose of 80 mg pasireotide long-acting release (LAR) i.m. followed by a dose-expansion phase (to evaluate safety and prelimi-nary efficacy). Associations between PK/pharmacodynamic parameters and clinical outcomes were evaluated using linear regression analysis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28720705/conceptual-framework-of-the-eco-physiological-phases-of-insect-diapause-development-justified-by-transcriptomic-profiling
#17
Vladimír Koštál, Tomáš Štětina, Rodolphe Poupardin, Jaroslava Korbelová, Alexander William Bruce
Insects often overcome unfavorable seasons in a hormonally regulated state of diapause during which their activity ceases, development is arrested, metabolic rate is suppressed, and tolerance of environmental stress is bolstered. Diapausing insects pass through a stereotypic succession of eco-physiological phases termed "diapause development." The phasing is varied in the literature, and the whole concept is sometimes criticized as being too artificial. Here we present the results of transcriptional profiling using custom microarrays representing 1,042 genes in the drosophilid fly, Chymomyza costata Fully grown, third-instar larvae programmed for diapause by a photoperiodic (short-day) signal were assayed as they traversed the diapause developmental program...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28720696/persistent-organic-pollutants-impair-insulin-secretory-function-of-pancreatic-beta-cells-human-and-in-vitro-evidence
#18
Yu-Mi Lee, Chae-Myeong Ha, Se-A Kim, Themis Thoudam, Young-Ran Yoon, Dae-Jung Kim, Hyeon-Chang Kim, Hyo-Bang Moon, Sungmi Park, In-Kyu Lee, Duk-Hee Lee
Persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), have emerged as a new risk factor of type 2 diabetes (T2D). We evaluated whether chronic exposure to low-dose POPs affects insulin secretory function of beta-cells in humans and in vitro cells. Serum concentrations of OCPs and PCBs were measured in 200 nondiabetic adults. Mathematical-model-based insulin secretion indices were estimated using a 2-hour 7-sample oral glucose tolerance test. Insulin secretion by INS1E beta-cells was measured after 48-hour treatment with 3 OCPs or a PCB mixture...
July 18, 2017: Diabetes
https://www.readbyqxmd.com/read/28720321/no-evidence-for-progressive-deterioration-in-stimulated-insulin-secretion-in-renal-transplant-recipients-after-12years-tacrolimus-exposure
#19
Mariëlle A C J Gelens, Johannes P van Hooff, Len Usvyat, Maarten H Christiaans
AIMS: Tacrolimus (Tac) inhibits insulin secretion in a Tac-trough blood level dependent way early post-transplant in renal transplant recipients (Rtx). It is unknown whether long-term exposure results into a progressive beta cells dysfunction. METHODS: Two independent cohorts of Tac-treated non-diabetic Rtx, previously participating in glucose metabolism studies using intravenous Glucose Tolerance Test (ivGTT) were included: Fifty-eight Rtx were tested by ivGTT cross-sectional between 0...
July 4, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28717164/glucagon-like-peptide-1-reduces-pancreatic-%C3%AE-cell-mass-through-hypothalamic-neural-pathways-in-high-fat-diet-induced-obese-rats
#20
Hisae Ando, Koro Gotoh, Kansuke Fujiwara, Manabu Anai, Seiichi Chiba, Takayuki Masaki, Tetsuya Kakuma, Hirotaka Shibata
We examined whether glucagon-like peptide-1 (GLP-1) affects β-cell mass and proliferation through neural pathways, from hepatic afferent nerves to pancreatic efferent nerves via the central nervous system, in high-fat diet (HFD)-induced obese rats. The effects of chronic administration of GLP-1 (7-36) and liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, c-fos expression and brain-derived neurotrophic factor (BDNF) content in the hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent sympathectomy (SpX)...
July 17, 2017: Scientific Reports
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