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https://www.readbyqxmd.com/read/28822958/therapeutic-molecules-against-type-2-diabetes-what-we-have-and-what-are-we-expecting
#1
REVIEW
Ashwini Kumar, Sudhanshu Kumar Bharti, Awanish Kumar
World Health Organization (WHO) has identified diabetes as one of the fastest growing non-communicable diseases with 422 million patients around the world in 2014. Diabetes, a metabolic disease, is characterized primarily by hyperglycemia which results in various macrovascular and microvascular complications like cardiovascular disease and neuropathies which can significantly deteriorate the quality of life. The body either does not manufactures enough insulin (type 1 diabetes or T1DM) or becomes insensitive to physiologically secreted insulin or both (type 2 diabetes or T2DM)...
April 9, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28822702/antibody-mediated-extreme-insulin-resistance-a-report-of-three-cases
#2
Han Na Kim, Betiel Fesseha, Laura Anzaldi, Allison Tsao, Panagis Galiatsatos, Aniket Sidhaye
BACKGROUND: Type 2 diabetes mellitus is characterized by relative insulin deficiency and insulin resistance. Features suggesting severe insulin resistance include acanthosis nigricans, hyperandrogenism, weight loss, and recurrent hospital admissions for diabetic ketoacidosis. In rare circumstances, hyperglycemia persists despite administration of massive doses of insulin. In these cases, it is important to consider autoimmune etiologies for insulin resistance such as type B insulin resistance and insulin antibody-mediated extreme insulin resistance, which carry high morbidity and mortality if untreated...
August 16, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28822390/physiologic-features-of-brain-death
#3
Eno-Obong Essien, Kristina Fioretti, Thomas M Scalea, Deborah M Stein
Brain death is known to be associated with physiologic derangements but their incidence is poorly described. Knowledge of the changes that occur during brain death is important for management of the potential organ donor. Thus, we sought to characterize the pathophysiology that occurs during brain death in patients with traumatic injuries. All brain-dead patients over a 10-year period were identified from the trauma registry at a level 1 urban trauma center. Patient demographics, injury characteristics, and clinical data for defining organ dysfunction were reviewed for the 24 hours surrounding brain-death declaration...
August 1, 2017: American Surgeon
https://www.readbyqxmd.com/read/28822091/effect-of-ap102-a-subtype-2-and-5-specific-somatostatin-analog-on-glucose-metabolism-in-rats
#4
Erika Tarasco, Petra Seebeck, Svende Pfundstein, Adrian F Daly, Philippe J Eugster, Alan G Harris, Eric Grouzmann, Thomas A Lutz, Christina N Boyle
PURPOSE: Somatostatin analogs are widely used to treat conditions associated with hormonal hypersecretion such as acromegaly and metastatic neuroendocrine tumors. First generation somatostatin analogs, such as octreotide and lanreotide, have high affinity for somatostatin receptor subtype 2 (SSTR2), but have incomplete efficacy in many patients. Pasireotide targets multiple SSTRs, having the highest affinity for SSTR5, but causes hyperglycemia and diabetes mellitus in preclinical and clinical studies...
August 18, 2017: Endocrine
https://www.readbyqxmd.com/read/28821742/rock-1-mediates-diabetes-induced-retinal-pigment-epithelial-and-endothelial-cell-blebbing-contribution-to-diabetic-retinopathy
#5
Pierre-Raphaël Rothschild, Sawsen Salah, Marianne Berdugo, Emmanuelle Gélizé, Kimberley Delaunay, Marie-Christine Naud, Christophe Klein, Alexandre Moulin, Michèle Savoldelli, Ciara Bergin, Jean-Claude Jeanny, Laurent Jonet, Yvan Arsenijevic, Francine Behar-Cohen, Patricia Crisanti
In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821456/hyperglycemia-is-associated-with-increased-bone-mineral-density-and-decreased-trabecular-bone-score-in-elderly-japanese-men-the-fujiwara-kyo-osteoporosis-risk-in-men-formen-study
#6
Masayuki Iki, Yuki Fujita, Katsuyasu Kouda, Akiko Yura, Takahiro Tachiki, Junko Tamaki, Renaud Winzenrieth, Yuho Sato, Jong-Seong Moon, Nozomi Okamoto, Norio Kurumatani
PURPOSE: Patients with type 2 diabetes mellitus (T2DM) have an increased fracture risk despite having higher areal bone mineral density (aBMD). This study aimed to clarify the association between glycemic and insulin resistance status and bone microarchitecture, and whether pentosidine and bone turnover markers play any roles in the association. METHODS: A total of 2012 community-dwelling men aged ≥65years completed baseline measurements of spine aBMD, fasting plasma glucose (FPG) and serum insulin, hemoglobin A1c (HbA1c), osteocalcin, type I procollagen N-terminal propeptide, type I collagen C-terminal crosslinking telopeptide, tartrate-resistant acid phosphatase isoenzyme 5b, pentosidine, height and weight and an interview regarding past disease history...
August 15, 2017: Bone
https://www.readbyqxmd.com/read/28821420/hyperglycemia-in-young-adults-seen-in-the-emergency-department-a-health-records-review
#7
Justin W Yan, Alexandra L Hamelin, Katherine M Gushulak, Kristine Van Aarsen, Melanie P Columbus, Ian G Stiell
Patients with diabetes who are in emerging adulthood, defined as the life stage between 18 and 29 years of age, have unique challenges in managing their illness and are at risk for acute complications and loss to follow up. This study's objective was to describe emergency department (ED) utilization because of hyperglycemia in emerging adults with diabetes and to characterize 30-day outcomes, including return visits and admission for hyperglycemia. This was a health-records review of emerging adults presenting over a 1-year period to 4 tertiary care EDs; the patients had known histories of diabetes and final diagnoses of hyperglycemia, diabetic ketoacidosis or hyperosmolar hyperglycemia...
August 15, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28820747/involvement-of-hyperglycemia-in-the-development-of-platelet-procoagulant-response-the-role-of-aldose-reductase-and-platelet-swelling
#8
Tomasz Rusak, Tomasz Misztal, Malgorzata Rusak, Justyna Branska-Januszewska, Marian Tomasiak
: Rise in mean platelet volume (MPV) has been demonstrated to be associated with increased platelet reactivity. In diabetes patients, augmented MPV was proposed to contribute to increased risk of thrombotic complications. Therefore, the aim of this study was to investigate whether under hyperglycemic conditions, aldose reductase (AR)-mediated sorbitol formation and associated rise in cell volume, which subsequently results in platelet hyperactivation. Platelets were obtained from 30 healthy volunteers and 13 patients with diabetes...
September 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28820679/tuberculosis-related-diabetes-is-it-reversible-after-complete-treatment
#9
Huma Aftab, Dirk L Christensen, Atiqa Ambreen, Mohammad Jamil, Peter Garred, Jørgen H Petersen, Susanne D Nielsen, Ib C Bygbjerg
Individuals with newly diagnosed tuberculosis (TB) were screened for diabetes (DM) with fasting plasma glucose (FPG) in Pakistan. A significant decrease in FPG was observed when TB was treated. Of those with newly diagnosed DM, 46% and 62% no longer had hyperglycemia after 3 and 6 months, respectively. Individuals with known DM also showed a significant decrease in fasting plasma levels when treated for TB, but after 3 months none had normoglycemia, and after 6 months 9.2% were normoglycemic. Thus, TB-related DM may abate when the stress terminates, as is the case in gestational DM...
August 7, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28819835/efficacy-and-safety-of-linagliptin-in-2681-asian-patients-stratified-by-age-obesity-and-renal-function-a-pooled-analysis-of-randomized-clinical-trials
#10
Guang Ning, Tushar Bandgar, Uwe Hehnke, Jisoo Lee, Juliana C N Chan
INTRODUCTION: Asian patients with type 2 diabetes (T2D) are younger, leaner, and more likely to develop renal dysfunction than White populations. In this multiethnic analysis of data from phase 3 trials, we investigated the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in Asians stratified by these subphenotypes. METHODS: Data from randomized, double-blind, placebo-controlled trials evaluating linagliptin (as monotherapy, add-on therapy to metformin ± sulfonylurea, combined with pioglitazone or added to insulin) were pooled with efficacy data from 11 randomized trials of at least 24 weeks and safety data from 15 trials of various durations...
August 17, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28819084/the-significance-of-lactate-and-lipid-peaks-for-predicting-primary-neuroepithelial-tumor-grade-with-proton-mr-spectroscopy
#11
Hisao Nakamura, Masatomo Doi, Takuya Suzuki, Yasuyuki Yoshida, Masahiro Hoshikawa, Masashi Uchida, Yuichiro Tanaka, Masayuki Takagi, Yasuo Nakajima
PURPOSE: (1)H-MRS is a non-invasive technique used to assess the metabolic activity of brain tumors. The technique is useful for the preoperative prediction of tumor grade, which is important for treatment planning and accurate prognosis. We used (1)H-MRS to study the lactate peak, which appears in various conditions, including hyperglycemia, ischemia, and hypoxia and lipid peak, which is associated with necrotic cells. The purpose of this study was to retrospectively examine the frequency and significance of lactate and lipid peaks in relation to brain tumor grade...
August 16, 2017: Magnetic Resonance in Medical Sciences: MRMS
https://www.readbyqxmd.com/read/28817755/measuring-toxic-effects-and-time-to-treatment-failure-for-nivolumab-plus-ipilimumab-in-melanoma
#12
Alexander N Shoushtari, Claire F Friedman, Pedram Navid-Azarbaijani, Michael A Postow, Margaret K Callahan, Parisa Momtaz, Katherine S Panageas, Jedd D Wolchok, Paul B Chapman
Importance: Nivolumab plus ipilimumab (nivo + ipi) is a standard treatment of advanced melanoma. Two randomized trials describe high objective response rates by Response Evaluation Criteria in Solid Tumors. The trials assessed toxic effects using the Common Terminology Criteria for Adverse Events (CTCAE), which may underestimate incidence of clinically significant immune-related adverse events (AEs). Objective: To describe detailed toxic effects and time to treatment failure of patients with melanoma treated with nivo + ipi in a prospective cohort...
August 17, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28816550/a-review-on-biosynthesis-analytical-techniques-and-pharmacological-activities-of-trigonelline-as-a-plant-alkaloid
#13
Neda Mohamadi, Fariba Sharififar, Mostafa Pournamdari, Mehdi Ansari
Trigonelline (TRG) as a polar hydrophilic alkaloid is extracted from many plant species, for example, Trigonella foenum-graecum, Allium sepapea, Coffea sp, Pissum sativum, Glycine max, and Lycopersicon esculentum. Numerous biological activities have been reported for TRG such as protection of heart and liver and treatment of hyperglycemia, hypercholesterolemia, nervous and hormonal disorders, and cancers. Thus, the aim of this review is to summarize some information about TRG's biosynthesis pathway, pharmacological activity, pharmacokinetics, and analytical techniques to introduce TRG as an alternative choice to treat the various diseases...
August 17, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28816105/thiazolidinedione-drugs-in-the-treatment-of-type-2-diabetes-mellitus-past-present-and-future
#14
Melissa A Davidson, Donald R Mattison, Laurent Azoulay, Daniel Krewski
Thiazolidinedione (TZD) drugs used in the treatment of type 2 diabetes mellitus (T2DM) have proven effective in improving insulin sensitivity, hyperglycemia, and lipid metabolism. Though well tolerated by some patients, their mechanism of action as ligands of peroxisome proliferator-activated receptors (PPARs) results in the activation of several pathways in addition to those responsible for glycemic control and lipid homeostasis. These pathways, which include those related to inflammation, bone formation, and cell proliferation, may lead to adverse health outcomes...
August 17, 2017: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/28815695/a-distinctive-histidine-residue-is-essential-for-in-vivo-glycation-inactivation-of-human-cd59-transgenically-expressed-in-mice-erythrocytes-implications-for-human-diabetes-complications
#15
Rupam Sahoo, Pamela Ghosh, Michael Chorev, Jose A Halperin
Clinical and experimental evidences support a link between the complement system and the pathogenesis of diabetes complications. CD59, an extracellular cell membrane-anchored protein, inhibits formation of the membrane attack complex (MAC), the main effector of complement-mediated tissue damage. This complement regulatory activity of human CD59 (hCD59) is inhibited by hyperglycemia-induced ε-amino glycation of Lys(41) . Biochemical and structural analyses of glycated proteins with known three-dimensional structure revealed that glycation of ε-amino lysyl residues occurs predominantly at "glycation motives" that include lysyl/lysyl pairs or proximity of a histidyl residue, in which the imidazolyl moiety is ≈ 5Å from the ε-amino group...
August 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28815569/glucose-dependent-leukocyte-activation-in-familial-hypercholesterolemia
#16
Natasja Koks, Marijke A de Vries, Erwin Birnie, Arash Alipour, Manuel Castro Cabezas
BACKGROUND: Leukocyte activation is an obligatory factor in the development of atherosclerosis. The postprandial situation has been associated to increased leukocyte activation in several disorders, such as type 2 diabetes mellitus and familial combined hyperlipidemia. Our study aim was to evaluate the effect of post-OGTT hyperglycemia on leukocyte activation in patients with familial hypercholesterolemia (FH). MATERIALS AND METHODS: Patients who met the diagnostic criteria for heterozygous FH and healthy volunteers were asked to undergo an oral glucose tolerance test...
August 16, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28815409/insulin-like-growth-factor-igf-pathway-targeting-in-cancer-role-of-the-igf-axis-and-opportunities-for-future-combination-studies
#17
Aaron Simpson, Wilfride Petnga, Valentine M Macaulay, Ulrike Weyer-Czernilofsky, Thomas Bogenrieder
Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair...
August 16, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28814814/umbilical-cord-extracts-improve-diabetic-abnormalities-in-bone-marrow-derived-mesenchymal-stem-cells-and-increase-their-therapeutic-effects-on-diabetic-nephropathy
#18
Kanna Nagaishi, Yuka Mizue, Takako Chikenji, Miho Otani, Masako Nakano, Yusaku Saijo, Hikaru Tsuchida, Shinichi Ishioka, Akira Nishikawa, Tsuyoshi Saito, Mineko Fujimiya
Bone marrow-derived mesenchymal stem cells (BM-MSC) has been applied as the most valuable source of autologous cell transplantation for various diseases including diabetic complications. However, hyperglycemia may cause abnormalities in intrinsic BM-MSC which might lose sufficient therapeutic effects in diabetic patients. We demonstrated the functional abnormalities in BM-MSC derived from both type 1 and type 2 diabetes models in vitro, which resulted in loss of therapeutic effects in vivo in diabetic nephropathy (DN)...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28813453/metabolomics-reveals-that-vine-tea-ampelopsis-grossedentata-prevents-high-fat-diet-induced-metabolism-disorder-by-improving-glucose-homeostasis-in-rats
#19
Wenting Wan, Baoping Jiang, Le Sun, Lijia Xu, Peigen Xiao
BACKGROUND: Vine tea (VT), derived from Ampelopsis grossedentata (Hand.-Mazz.) W.T. Wang, is an alternative tea that has been consumed widely in south China for hundreds of years. It has been shown that drinking VT on a daily basis improves hyperlipidemia and hyperglycemia. However, little is known about the preventive functions of VT for metabolic dysregulation and the potential pathological mechanisms involved. This paper elucidates the preventive effects of VT on the dysregulation of lipid and glucose metabolism using rats maintained on a high-fat-diet (HFD) in an attempt to explain the potential mechanisms involved...
2017: PloS One
https://www.readbyqxmd.com/read/28813209/galangin-a-natural-flavonoid-reduces-mitochondrial-oxidative-damage-in-streptozotocin-induced-diabetic-rats
#20
Amal A Aloud, Chinnadurai Veeramani, Chandramohan Govindasamy, Mohammed A Alsaif, Khalid S Al-Numair
OBJECTIVE: We designed this study to observe the effect of galangin on damaged mitochondria in the liver of diabetic rats. METHODS: Male albino Wistar rats were made diabetic by injecting streptozotocin (STZ) intraperitoneally (40 mg kg(-1) body weight (BW)). Galangin (8 mg kg(-1) BW) or glibenclamide (600 µg kg(-1) BW) was given orally daily once for 45 days to both healthy and diabetic rats. RESULTS: Diabetic rats showed significant (P < 0...
August 16, 2017: Redox Report: Communications in Free Radical Research
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