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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/28340044/oral-ghrelin-receptor-agonist-mk-0677-increases-serum-insulin-like-growth-factor-1-in-hemodialysis-patients-a-randomized-blinded-study
#2
Garland A Campbell, James T Patrie, Bruce D Gaylinn, Michael O Thorner, Warren K Bolton
Background: . Protein-energy wasting (PEW) in end-stage renal disease (ESRD) patients is associated with increased morbidity and mortality, but options for treatment are limited. Growth hormone (GH) increases insulin-like growth factor 1 (IGF-1), with improved nutritional parameters, but must be given subcutaneously and does not provide normal GH secretion patterns. MK-0677, an oral ghrelin receptor agonist (GRA), maintains normal GH secretion and increases lean body mass in normal subjects; it has not been studied in dialysis patients, an essential step in assessing efficacy and safety prior to clinical trials...
March 3, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28337819/pai-1-in-granulosa-cells-is-suppressed-directly-by-statin-and-indirectly-by-suppressing-tgf-%C3%AE-and-tnf-%C3%AE-in-mononuclear-cells-by-insulin-sensitizing-drugs
#3
Kaori Yamada-Nomoto, Osamu Yoshino, Ikumi Akiyama, Akira Iwase, Yosuke Ono, Tomoko Nakamura, Miyuki Harada, Akitoshi Nakashima, Tomoko Shima, Akemi Ushijima, Yutaka Osuga, Russell Jeffrey Chang, Shunichi Shimasaki, Shigeru Saito
PROBLEM: Plasminogen activator inhibitor-1 (PAI-1) is elevated in women with polycystic ovary syndrome (PCOS), but the regulation in granulosa cells (GCs) is unclear. METHOD OF STUDY: PAI-1 expression in PCOS ovaries was investigated immunohistologically. PAI-1 expressions in HGrC1, a human GC cell line, were investigated at mRNA and activity levels. The expressions of TGF-β and TNF-α in peritoneal fluid mononuclear cells (PFMCs) were measured with quantitative PCR...
March 24, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28337685/type-iii-hypersensitivity-reaction-to-subcutaneous-insulin-preparations-in-a-type-1-diabetic
#4
Benjamin R Murray, Jolene R Jewell, Kyle J Jackson, Olabunmi Agboola, Brianna R Alexander, Poonam Sharma
Management of type 1 diabetes in patients who have insulin hypersensitivity is a clinical challenge and places patients at risk for recurrent diabetic ketoacidosis (DKA). Hypersensitivity reactions can be due to the patient's response to the insulin molecule itself or one of the injection's non-insulin components. It is therefore crucial for clinicians to quickly recognize the type of hypersensitivity reaction that is occurring and identify potentially immunogenic additives for the purpose of directing therapy as various insulin preparations have differing ingredients...
March 23, 2017: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/28336399/synthetic-matrix-of-polyether-polyurethane-as-a-biological-platform-for-pancreatic-regeneration
#5
Luciana Xavier Pereira, Celso Tarso Rodrigues Viana, Laura Alejandra Ariza Orellano, Simone Aparecida de Almeida, Anilton Cesar Vasconcelos, Alfredo de Miranda Goes, Alexander Birbrair, Silvia Passos Andrade, Paula Peixoto Campos
AIMS: Several alternative cellular approaches using biomaterials to host insulin-producing cells derived from stem cells have been developed to overcome the limitations of type 1 diabetes treatment (exogenous insulin injection). However, none seem to fulfill all requirements needed to induce pancreatic cells successful colonization of the scaffolds. Here, we report a polymeric platform adherent to the native mice pancreas filled with human adipose stem cells (hASCs) that was able to induce growth of pancreatic parenchyma...
March 20, 2017: Life Sciences
https://www.readbyqxmd.com/read/28335697/investigation-of-a-lifestyle-intervention-in-women-at-high-risk-of-breast-cancer
#6
Claire J Han, Larissa A Korde, Scott Reding, Kristen Allott, Matt Van Doren, Yvonne Schwarz, Catalina Vaughan, Kerryn W Reding
One fourth of breast cancer can be attributed to sedentary lifestyles and being overweight or obese. This pilot study was conducted to explore whether a 6-month lifestyle intervention affected body composition and obesity-related biomarkers among women at high risk of breast cancer. Overweight/obese women at high risk of breast cancer were randomized to the control group or to the intervention. The intervention was an individually tailored, cognitive-behavioral therapy program that assists women in identifying strategies to improve their nutrition and physical activity habits with the goal of reduced adiposity...
March 1, 2017: Western Journal of Nursing Research
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
#7
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/28335087/ursolic-acid-and-mechanisms-of-actions-on-adipose-and-muscle-tissue-a-systematic-review
#8
REVIEW
Carlos K Katashima, Vagner R Silva, Tatyanne L Gomes, Claude Pichard, Gustavo D Pimentel
This systematic review aimed at addressing the ursolic acid actions as an adjunctive treatment of the obesity-mediated metabolic abnormalities. To explore our aims, we used the literature search including clinical and animal studies using the Medline and Google Scholar (up to December 2015). Out of 63 screened studies, 17 presented eligibility criteria, such as the use of ursolic acid on adiposity, energy expenditure and skeletal muscle mass in mice and humans. In the literature, we found that several physiological and molecular mechanisms are implicated in the effects of ursolic acid on obesity, energy expenditure, hepatic steatosis, skeletal muscle mass loss and physical fitness, such as (1) increase of thermogenesis by modulation adipocyte transcription factors, activation of 5' adenosine monophosphate-activated protein kinase and overexpression of the uncoupling protein 1 thermogenic marker; (2) enhancement of skeletal muscle mass by activation in bloodstream growth hormone and insulin-like growth factor-1 concentrations secretion, as well as in the activation of mammalian target of rapamycin and inhibition of ring-finger protein-1; and (3) improvement of physical fitness by skeletal muscle proliferator-activated receptor gamma co-activator alpha and sirtuin 1 expression...
March 23, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28334746/a-newborn-with-transient-diabetes-mellitus-accompanied-by-ketoacidosis-attributable-to-a-zfp57-mutation
#9
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
#10
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/28334539/-long-acting-insulins-in-the-treatment-of-type-2%C3%A2-diabetes-and-their-position-in-the-current-treatment-algorithm
#11
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/28331986/renal-function-preservation-with-pioglitazone-or-with-basal-insulin-as-an-add-on-therapy-for-patients-with-type-2-diabetes-mellitus
#12
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/28331909/evaluating-the-effect-of-insulin-sensitizers-metformin-and-pioglitazone-alone-and-in-combination-on-women-with-polycystic-ovary-syndrome-an-rct
#13
Seyed Mojtaba Sohrevardi, Fahime Nosouhi, Saeed Hossein Khalilzade, Parichehr Kafaie, Mojgan Karimi-Zarchi, Iman Halvaei, Mehdi Mohsenzadeh
BACKGROUND: Insulin resistance and hyperinsulinemia may play a role in pathogenesis of PCOS. One of the common therapeutic methods is using insulin-sensitizing drugs such as metformin and thiazolidinediones. OBJECTIVE: The purpose was to determine the effect of metformin and pioglitazone on clinical, hormonal and metabolic parameters in women with PCOS. MATERIALS AND METHODS: Eighty four women randomly received one of the following for 3 months: metformin (n=28) (500 mg three times a day), pioglitazone (30 mg daily) (n=28) and combination of both metformin and pioglitazone (n=28) (30 mg/day pioglitazone plus 500 mg metformin three times a day)...
December 2016: International Journal of Reproductive Biomedicine (Yazd, Iran)
https://www.readbyqxmd.com/read/28331865/growth-hormone-utilization-review-in-a-pediatric-primary-care-setting
#14
Fatemeh Sayarifard, Fereshteh Bakhshi Imcheh, Shirinsadat Badri, Toktam Faghihi, Mostafa Qorbani, Mania Radfar
OBJECTIVE: One of the main problems facing public health providers and administrators in many countries is ensuring the rational use of high-cost drugs. In this regard, on-going process of medication use evaluation can be considered as a useful tool. In this study, we evaluated certain usage aspects of a highly-cost medication, that is, recombinant growth hormone (GH). METHODS: This cross-sectional study conducted from August 2012 to August 2014. Children receiving GH ± gonadotropin releasing hormone (GnRH) analogs were included in the study...
January 2017: Journal of Research in Pharmacy Practice
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/28331351/long-term-management-of-type-2-diabetes-with-glucagon-like-peptide-1-receptor-agonists
#17
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/28330997/igfbp3-modulates-lung-tumorigenesis-and-cell-growth-through-igf1-signaling
#18
Yong A Wang, Yunguang Sun, Joshua D Palmer, Charalambos Solomides, Li-Ching Huang, Yu Shyr, Adam P Dicker, Bo Lu
Insulin-like growth factor binding protein 3 (IGFBP3) modulates cell growth through IGF-dependent and -independent mechanisms. Reports suggest that the serum levels of IGFBP3 are associated with various cancers and that IGFBP3 expression is significantly decreased in cisplatin (CDDP)-resistant lung cancer cells. Based on these findings, we investigated whether Igfbp3 deficiency accelerates mouse lung tumorigenesis and if expression of IGFBP3 enhances CDDP response by focusing on the IGF1 signaling cascade. To this end, an Igfbp3-null mouse model was generated in combination with KrasG12D to compare the tumor burden...
March 22, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28330852/a-controlled-release-mitochondrial-protonophore-reverses-hypertriglyceridemia-nonalcoholic-steatohepatitis-and-diabetes-in-lipodystrophic-mice
#19
Abudukadier Abulizi, Rachel J Perry, João Paulo G Camporez, Michael J Jurczak, Kitt Falk Petersen, Patricia Aspichueta, Gerald I Shulman
Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes...
March 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28330649/effect-of-sacubitril-valsartan-versus-enalapril-on-glycaemic-control-in-patients-with-heart-failure-and-diabetes-a-post-hoc-analysis-from-the-paradigm-hf-trial
#20
Jelena P Seferovic, Brian Claggett, Sara B Seidelmann, Ellen W Seely, Milton Packer, Michael R Zile, Jean L Rouleau, Karl Swedberg, Martin Lefkowitz, Victor C Shi, Akshay S Desai, John J V McMurray, Scott D Solomon
BACKGROUND: Diabetes is an independent risk factor for heart failure progression. Sacubitril/valsartan, a combination angiotensin receptor-neprilysin inhibitor, improves morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), compared with the angiotensin-converting enzyme inhibitor enalapril, and improves peripheral insulin sensitivity in obese hypertensive patients. We aimed to investigate the effect of sacubitril/valsartan versus enalapril on HbA1c and time to first-time initiation of insulin or oral antihyperglycaemic drugs in patients with diabetes and HFrEF...
March 17, 2017: Lancet Diabetes & Endocrinology
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