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https://www.readbyqxmd.com/read/28432748/future-challenges-and-therapeutic-opportunities-in-type-2-diabetes-changing-the-paradigm-of-current-therapy
#1
REVIEW
D R Owens, L Monnier, A H Barnett
Most algorithms for type 2 diabetes mellitus (T2DM) do not recommend treatment escalation until glycated haemoglobin (HbA1c) fails to reach the recommended target of 7% (53 mmol/mol) within approximately 3 months on any treatment regimen ('treat to failure'). Clinical inertia and/or poor adherence to therapy contribute to patients not reaching glycaemic targets when managed according to this paradigm. Clinical inertia exists across the entire spectrum of anti-diabetes therapies, although it is most pronounced when initiating and optimizing insulin therapy...
April 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28431540/prevention-of-advanced-glycation-end-products-formation-in-diabetic-rats-through-beta-cell-modulation-by-aegle-marmelos
#2
Rahman M Hafizur, Shahrukh Momin, Noor Fatima
BACKGROUND: Although the anti-diabetic activity of Aegle marmelos (AM) is known, however, its anti-glycation activity is not reported yet. In this study, we have investigated its anti-glycation activity under in vitro and in vivo conditions and determined possible mechanism(s) in streptozotocin-induced diabetic rats. METHODS: Effective dose of AM (400 mg/kg) was administrated orally to diabetic rats for 42 days. Thereafter, blood glucose, serum insulin, HbA1c, antioxidant status, and advanced glycation end-products (AGEs) were measured...
April 21, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28428951/the-effect-of-flour-from-the-rind-of-the-yellow-passion-fruit-on-glycemic-control-of-people-with-diabetes-mellitus-type-2-a-randomized-clinical-trial
#3
Márcio Flávio Moura de Araújo, Vivian Saraiva Veras, Roberto Wagner Júnior Freire de Freitas, Maria do Livramento de Paula, Thiago Moura de Araújo, Lilian Raquel Alexandre Uchôa, Maria Wendiane Gueiros Gaspar, Maria da Conceição do Santos Oliveira Cunha, Maria Aparecida Alves de Oliveira Serra, Carolina Maria de Lima Carvalho, Edmara Chaves Costa, Marta Maria Coelho Damasceno
BACKGROUND: The single or combined use of herbal and dietary products with medications has shown benefits in the metabolic modulation of carbohydrates, in the restoring of the function of pancreatic beta cells, and in insulin resistance. To analyze the effect of the use of flour made from the rind of the yellow passion fruit on the glycemic control of people with diabetes mellitus type 2. METHODS: An open, prospective, randomized clinical trial was undertaken with 54 participants over an eight-week period...
2017: Journal of Diabetes and Metabolic Disorders
https://www.readbyqxmd.com/read/28428013/-the-monophasic-pattern-in-oral-glucose-tolerance-test-as-a-predictive-risk-factor-of-type-2-diabetes-in-obese-paediatric-patients
#4
Aura D Herrera-Martínez, Patricia Enes, María Martín-Frías, Belén Roldán, Rosa Yelmo, Raquel Barrio
INTRODUCTION: The onset of obesity at young ages is strongly associated with the early development of type 2diabetes (T2D). The shape of the curves of glucose and insulin curves during an oral glucose tolerance test (OGTT) could predict the risk of developing T2D. OBJECTIVE: To analyse the morphology of the OGTT and determine T2D risk factors in a mainly Caucasian population of children and adolescents. METHODS: Observational retrospective study including 588 patients (309 males, 279 females) with a mean age of 11...
April 17, 2017: Anales de Pediatría: Publicación Oficial de la Asociación Española de Pediatría (A.E.P.)
https://www.readbyqxmd.com/read/28423063/vitamin-d-status-and-its-association-with-insulin-resistance-among-type-2-diabetics-a-case-control-study-in-ghana
#5
Linda Ahenkorah Fondjo, William K B A Owiredu, Samuel Asamoah Sakyi, Edwin Ferguson Laing, Michael Acquaye Adotey-Kwofie, Enoch Odame Antoh, Eric Detoh
BACKGROUND: Vitamin D plays a major role in physiological processes that modulate mineral metabolism and immune function with probable link to several chronic and infectious conditions. Emerging data suggests a possible influence of vitamin D on glucose homeostasis. This study sought to provide preliminary information on vitamin D status among Ghanaian type 2 diabetics and assessed its association with glucose homeostasis. METHODS: In a case control study, 118 clinically diagnosed Type 2 Diabetes Mellitus (T2DM) patients attending Diabetic Clinic at the Nkawie Government Hospital were enrolled between October and December 2015...
2017: PloS One
https://www.readbyqxmd.com/read/28422431/effect-of-empagliflozin-on-tacrolimus-induced-pancreas-islet-dysfunction-and-renal-injury
#6
J Jin, L Jin, K Luo, S W Lim, B H Chung, C W Yang
An inhibitor of sodium glucose co-transporter type 2 (SGLT-2) is recommended in type 2 diabetes mellitus (DM) but its use is still undetermined in Tacrolimus (TAC)-induced DM. We evaluated the effect of empagliflozin (Em) on TAC-induced pancreatic islet dysfunction and renal injury in experimental model of TAC-induced DM and in vitro. TAC induced a two-fold increase in SGLT-2 expression, while Em decreased SGLT-2 expression and further increased urinary glucose excretion compared to the TAC group. Em reduced hyperglycemia and increased plasma insulin level, pancreatic islet size and glucose-stimulated insulin secretion (GSIS) compared to the TAC group...
April 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28422176/the-characteristics-of-newly-diagnosed-adult-early-onset-diabetes-a-population-based-cross-sectional-study
#7
Xiantong Zou, Xianghai Zhou, Linong Ji, Wenying Yang, Juming Lu, Jianping Weng, Weiping Jia, Zhongyan Shan, Jie Liu, Haoming Tian, Qiuhe Ji, Dalong Zhu, Jiapu Ge, Lixiang Lin, Li Chen, Xiaohui Guo, Zhigang Zhao, Qiang Li, Zhiguang Zhou
To investigate the characteristics of newly diagnosed early-onset diabetes in the Chinese population, 2801 newly diagnosed diabetes participants without known diabetes or pre-diabetes in a national cross-sectional survey were analysed. Participants were divided into quartiles (22-43, 44-52, 53-61 and >61 years) according to age of diabetes onset and the first group were defined as early-onset diabetes group. Early-onset diabetes group had lower systolic blood pressure (SBP), total cholesterol, low density lipoprotein cholesterol, 2-hour post prandial blood glucose and urine albumin creatinine ratio...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420418/adult-muscle-derived-stem-cells-engraft-and-differentiate-into-insulin-expressing-cells-in-pancreatic-islets-of-diabetic-mice
#8
Violeta Mitutsova, Wendy Wai Yeng Yeo, Romain Davaze, Celine Franckhauser, El-Habib Hani, Syahril Abdullah, Patrice Mollard, Marie Schaeffer, Anne Fernandez, Ned J C Lamb
BACKGROUND: Pancreatic beta cells are unique effectors in the control of glucose homeostasis and their deficiency results in impaired insulin production leading to severe diabetic diseases. Here, we investigated the potential of a population of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to differentiate in vitro into beta cells when transplanted as undifferentiated stem cells in vivo to compensate for beta-cell deficiency. RESULTS: In vitro, cultured MDSC spontaneously differentiated into insulin-expressing islet-like cell clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry under the control of an insulin promoter...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28419211/the-inhibitory-g-protein-%C3%AE-subunit-g%C3%AE-z-promotes-type-1-diabetes-like-pathophysiology-in-nod-mice
#9
Rachel J Fenske, Mark T Cadena, Quincy E Harenda, Haley N Wienkes, Kathryn Carbajal, Michael D Schaid, Erin Laundre, Allison L Brill, Nathan A Truchan, Harpreet Brar, Jaclyn Wisinski, Jinjin Cai, Timothy E Graham, Feyza Engin, Michelle E Kimple
The alpha subunit of the heterotrimeric Gz protein, Gαz, promotes beta-cell death and inhibits beta-cell replication when pancreatic islets are challenged by stressors. Thus, we hypothesized that loss of Gαz protein would preserve functional beta-cell mass in the non-obese diabetic (NOD) model, protecting from overt diabetes. We saw that protection from diabetes was robust and durable up to 35 weeks of age in Gαz knockout mice. By 17 weeks of age, Gαz-null NOD mice had significantly higher diabetes-free survival than wild-type littermates...
April 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28413178/synthesized-a%C3%AE-42-caused-intracellular-oxidative-damage-leading-to-cell-death-via-lysosome-rupture
#10
Yuki Oku, Kazuma Murakami, Kazuhiro Irie, Jun Hoseki, Yasuyoshi Sakai
Neuronal cellular accumulation of amyloid beta peptide (Aβ) has been implicated in the pathogenesis of Alzheimer’s disease (AD). Intracellular accumulation of Aβ42, a toxic form of Aβ, was observed as an early event in AD patients. However, its contribution and the cellular mechanism of cell death remained unclear. We herein revealed the mechanism by which Aβ42 incorporated into cells leads to cell death by using chemically synthesized Aβ42 variants. The Aβ42 variant Aβ42 (E22P) which has an increased tendency to oligomerize, accumulated in lysosomes at an earlier stage than wild-type Aβ42, leading to higher ROS production and lysosomal membrane oxidation, and resulting in cell death...
April 12, 2017: Cell Structure and Function
https://www.readbyqxmd.com/read/28409274/toward-molecular-imaging-of-the-free-fatty-acid-receptor-1
#11
Ewa Hellström-Lindahl, Ola Åberg, Cecilia Ericsson, Gavin O'Mahony, Peter Johnström, Stanko Skrtic, Olof Eriksson
AIMS: Molecular imaging of the free fatty acid receptor 1 (FFAR1) would be a valuable tool for drug development by enabling in vivo target engagement studies in human. It has also been suggested as a putative target for beta cell imaging, but the inherent lipophilicity of most FFAR1 binders produces high off-target binding, which has hampered progress in this area. The aim of this study was to generate a suitable lead compound for further PET labeling. METHODS: In order to identify a lead compound for future PET labeling for quantitative imaging of FFAR1 in human, we evaluated tritiated small molecule FFAR1 binding probes ([(3)H]AZ1, [(3)H]AZ2 and [(3)H]TAK-875) for their off-target binding, receptor density and affinity in human pancreatic tissue (islets and exocrine) and rodent insulinoma...
April 13, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28409212/trajectories-of-glycaemia-insulin-sensitivity-and-insulin-secretion-in-south-asian-and-white-individuals-before-diagnosis-of-type-2-diabetes-a-longitudinal-analysis-from-the-whitehall-ii-cohort-study
#12
Adam Hulman, Rebecca K Simmons, Eric J Brunner, Daniel R Witte, Kristine Færch, Dorte Vistisen, Satoyo Ikehara, Mika Kivimaki, Adam G Tabák
AIMS/HYPOTHESIS: South Asian individuals have reduced insulin sensitivity and increased risk of type 2 diabetes compared with white individuals. Temporal changes in glycaemic traits during middle age suggest that impaired insulin secretion is a particular feature of diabetes development among South Asians. We therefore aimed to examine ethnic differences in early changes in glucose metabolism prior to incident type 2 diabetes. METHODS: In a prospective British occupational cohort, subject to 5 yearly clinical examinations, we examined ethnic differences in trajectories of fasting plasma glucose (FPG), 2 h post-load plasma glucose (2hPG), fasting serum insulin (FSI), 2 h post-load serum insulin (2hSI), HOMA of insulin sensitivity (HOMA2-S) and secretion (HOMA2-B), and the Gutt insulin sensitivity index (ISI0,120) among 120 South Asian and 867 white participants who developed diabetes during follow-up (1991-2013)...
April 13, 2017: Diabetologia
https://www.readbyqxmd.com/read/28407415/impact-of-insulin-glargine-and-lixisenatide-on-beta-cell-function-in-patients-with-type-2-diabetes-mellitus-a-randomized-open-label-study
#13
Juris J Meier, Nina Schenker, Melanie Kahle, Freimut Schliess, Christoph Kapitza, Bjoern A Menge
Beta-cell function can be enhanced by direct stimulation of insulin secretion or by induction of beta-cell rest. Whether both strategies can complement each other has not yet been examined. 28 subjects with type 2 diabetes (HbA1c 7.8 ± 0.5 %) were treated with either lixisenatide or titrated insulin glargine, followed by their combined administration each over four weeks. First and second phase insulin secretion during an i.v. glucose challenge were calculated. First- and second-phase insulin secretion were not increased with glargine alone, but increased after addition of lixisenatide (p < 0...
April 13, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28405576/evaluation-of-anti-diabetic-activity-of-ahpl-aytab-0513-tablet-in-streptozotocin-induced-diabetes-in-rats
#14
Sanjay U Nipanikar, Soham S Chitlange, Dheeraj Nagore
BACKGROUND: Diabetes is a chronic, progressive disease associated with several complications leading to significant mortality and morbidity. Limitations and drawbacks of the conventional treatment generate need for safer, effective complimentary therapies to prevent complications, and maintain normoglycemic status. AIM AND OBJECTIVES: The aim of this study is to to evaluate antidiabetic activity of AHPL/AYTAB/0513 tablet alone, oral hypoglycemic agents (OHA[s]), and combination of AHPL/AYTAB/0513 tablet and OHA(s) in streptozotocin-induced diabetes in rats...
January 2017: International Journal of Pharmaceutical Investigation
https://www.readbyqxmd.com/read/28405188/compound-19e-a-novel-glucokinase-activator-protects-against-cytokine-induced-beta-cell-apoptosis-in-ins-1-cells
#15
Yoon Sin Oh, Eunhui Seo, Kaapjoo Park, Hee-Sook Jun
Previously, compound 19e, a novel heteroaryl-containing benzamide derivative, was identified as a potent glucokinase activator (GKA) and showed a glucose-lowering effect in diabetic mice. In this study, the anti-apoptotic actions of 19e were evaluated in INS-1 pancreatic beta-cells co-treated with TNF-α and IL-1β to induce cell death. Compound 19e protected INS-1 cells from cytokine-induced cell death, and the effect was similar to treatment with another GKA or exendin-4. Compound 19e reduced annexin-V stained cells and the expression of cleaved caspase-3 and poly (ADP-ribose) polymerase protein, as well as upregulated the expression of B-cell lymphoma-2 protein...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28404787/novel-atp-synthase-independent-mechanism-coupling-mitochondrial-activation-to-exocytosis-in-insulin-secreting-cells
#16
Umberto De Marchi, Aurelie Hermant, Jonathan Thevenet, Yann Ratinaud, Jaime Santo-Domingo, Denis Barron, Andreas Wiederkehr
Pancreatic beta-cells sense glucose promoting insulin secretion. Glucose sensing requires the sequential stimulation of glycolysis, mitochondrial metabolism and Ca(2+) entry. To elucidate how mitochondrial activation in beta-cells contributes to insulin secretion, we have compared the effects of glucose and the mitochondrial substrate methylsuccinate in INS-1E insulin secreting cells, at the respective concentrations they maximally activate mitochondrial respiration. Both substrates induced insulin secretion with distinct respiratory profiles, mitochondrial hyperpolarization, NADH production and ATP/ADP ratios...
April 12, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28402852/an-activating-stat3-mutation-causes-neonatal-diabetes-through-premature-induction-of-pancreatic-differentiation
#17
Jonna Saarimäki-Vire, Diego Balboa, Mark A Russell, Juha Saarikettu, Matias Kinnunen, Salla Keskitalo, Amrinder Malhi, Cristina Valensisi, Colin Andrus, Solja Eurola, Heli Grym, Jarkko Ustinov, Kirmo Wartiovaara, R David Hawkins, Olli Silvennoinen, Markku Varjosalo, Noel G Morgan, Timo Otonkoski
Activating germline mutations in STAT3 were recently identified as a cause of neonatal diabetes mellitus associated with beta-cell autoimmunity. We have investigated the effect of an activating mutation, STAT3(K392R), on pancreatic development using induced pluripotent stem cells (iPSCs) derived from a patient with neonatal diabetes and pancreatic hypoplasia. Early pancreatic endoderm differentiated similarly from STAT3(K392R) and healthy-control cells, but in later stages, NEUROG3 expression was upregulated prematurely in STAT3(K392R) cells together with insulin (INS) and glucagon (GCG)...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28401888/advances-in-pancreatic-islet-monolayer-culture-on-glass-surfaces-enable-super-resolution-microscopy-and-insights-into-beta-cell-ciliogenesis-and-proliferation
#18
Edward A Phelps, Chiara Cianciaruso, Jaime Santo-Domingo, Miriella Pasquier, Gabriele Galliverti, Lorenzo Piemonti, Ekaterine Berishvili, Olivier Burri, Andreas Wiederkehr, Jeffrey A Hubbell, Steinunn Baekkeskov
A robust and reproducible method for culturing monolayers of adherent and well-spread primary islet cells on glass coverslips is required for detailed imaging studies by super-resolution and live-cell microscopy. Guided by an observation that dispersed islet cells spread and adhere well on glass surfaces in neuronal co-culture and form a monolayer of connected cells, we demonstrate that in the absence of neurons, well-defined surface coatings combined with components of neuronal culture media collectively support robust attachment and growth of primary human or rat islet cells as monolayers on glass surfaces...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28401743/portosystemic-shunt-as-a-cause-of-congenital-hyperinsulinemic-hypoglycemia
#19
Keisuke Yoshii, Masahiro Noda, Yasuhiro Naiki, Reiko Horikawa
Congenital hyperinsulinemic hypoglycemia (CHH) is characterized by the inappropriate secretion of insulin from pancreatic beta cells in the presence of hypoglycemia. We herein describe the case of a 5-month-old boy with CHH due to congenital portosystemic shunt (CPSS). Insulin secreted from pancreatic beta cells flows into the portal vein and is first metabolized in the liver. First-pass elimination of insulin in the liver leads to great decrease in insulin concentration by approximately 40-80% in humans. CPSS accounts for a large quantity of insulin delivery into the systemic circulation due to the lack of hepatic first-pass elimination...
April 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28400827/effects-of-vitamin-d-deficiency-treatment-on-metabolic-markers-in-hashimoto-thyroiditis-patients
#20
Parichehr Vahabi Anaraki, Ashraf Aminorroaya, Massoud Amini, Awat Feizi, Bijan Iraj, Azamosadat Tabatabaei
BACKGROUND: The aim of the current trial was to investigate the effect of Vitamin D treatment on metabolic markers in people with Vitamin D deficiency and thyroid autoimmunity. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled clinical trial, 65 Vitamin D deficient euthyroid or hypothyroid patients with positive TPO-Ab were enrolled. They randomly allocated into two groups to receive oral Vitamin D3 (50000 IU weekly) and placebo for 12 weeks...
2017: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
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