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Mohun Ramratnam, Barrett Kenny, John W Kyle, Brandi Wiedmeyer, Timothy A Hacker, David Y Barefield, Elizabeth M McNally, Jonathan C Makielski
ATP-sensitive potassium channels found in both the sarcolemma (sarcKATP ) and mitochondria (mitoKATP ) of cardiomyocytes are important mediators of cardioprotection during ischemic heart disease. Sulfonylurea receptor isoforms (SUR2), encoded by Abcc9 , an ATP-binding cassette family member, form regulatory subunits of the sarcKATP channel and are also thought to regulate mitoKATP channel activity. A short-form splice variant of SUR2 (SUR2A-55) was previously shown to target mitochondria and display diaxoxide and ATP insensitive KATP activity when co-expressed with the inward rectifier channels Kir6...
July 2018: Heliyon
Christian Seerup Frandsen, Thomas Fremming Dejgaard, Sten Madsbad, Jens Juul Holst
Despite intensified insulin treatment, many persons with type 1 diabetes (T1D) do not achieve glycemic and metabolic targets. Consequently, non-insulin chemical therapies that improve glycemic control and metabolic parameters without increasing the risk of adverse events (including hypoglycemia) are of interest as adjunct therapies to insulin. Areas covered: In this review, the authors discuss the efficacy and safety of non-insulin therapies, including pramlintide, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 inhibitors (DPP-4), sodium-glucose cotransporter (SGLT1 and SGLT2) inhibitors, metformin, sulfonylureas, and thiazolidinediones as add-on therapies to insulin in T1D...
June 2018: Expert Opinion on Pharmacotherapy
Kenta Nakano, Rieko Yanobu-Takanashi, Yuki Takahashi, Hayato Sasaki, Yukiko Shimizu, Tadashi Okamura, Nobuya Sasaki
AIMS/INTRODUCTION: Diabetic animal models have made an enormous contribution to our understanding of the etiology of diabetes and the development of new medications. The aim of this study was to develop and characterize a novel, non-obese murine strain with spontaneous diabetes, the insulin hyposecretion (ihs) mouse. MATERIALS AND METHODS: During the development of ICGN.B6-Tns2WT  strain as the control for ICGN-Tns2nph  congenital nephrotic strain, diabetic mice were discovered and named ihs mice...
July 10, 2018: Journal of Diabetes Investigation
Michelle L Baglia, Yong Cui, Tao Zheng, Gong Yang, Honglan Li, Mingrong You, Liling Xu, Harvey Murff, Yu-Tang Gao, Wei Zheng, Yong-Bing Xiang, Xiao-Ou Shu
Purpose: Studies suggest that regular use of metformin may decrease cancer mortality. We investigated the association between diabetes medication use and cancer survival. Materials and Methods: The current study includes 633 breast, 890 colorectal, 824 lung, and 543 gastric cancer cases identified from participants of two population-based cohort studies in Shanghai. Information on diabetes medication use was obtained by linking to electronic medical records. The associations between diabetes medication use (metformin, sulfonylureas, and insulin) and overall and cancer-specific survival were evaluated using time-dependent Cox proportional hazards models...
July 2, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Jiun-Ling Wang, Yaa-Hui Dong, Wen-Chien Ko, Chia-Hsuin Chang, Li-Chiu Wu, Lee-Ming Chuang, Pau-Chung Chen
AIM: Previous research has suggested that peroxisome proliferator-activated receptor-gamma (PPAR-γ) may play an important role in immunomodulation. We aimed to examine the association between thiazolidinediones, PPAR-γ agonists, and incidence of bacterial abscess among patients with type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study included 46,986 propensity (PS)-matched patients diagnosed with type 2 diabetes between 2000 and 2010. We compared incidence of bacterial abscess, including liver and non-liver abscesses, between patients treated with metformin plus a thiazolidinedione (M+T, N=7831) or metformin plus a sulfonylurea (M+S, N=39,155)...
July 4, 2018: Diabetes, Obesity & Metabolism
Camila P Mendes, Bárbara G Postal, Geisel T C Oliveira, Allisson J G Castro, Marisa J S Frederico, Ana L L Moraes, Patrícia D Neuenfeldt, Ricardo J Nunes, Danusa Menegaz, Fátima R M B Silva
New compounds with promising antidiabetic activity were synthesized. For the first time, a portion of the glibenclamide molecule was bound to a part of the core structure of thiazolidinedione to evaluate insulin secretagogue activity. Following studies in our laboratory, 4-{2-[2-(3,4-dichlorophenyl)-4-oxo-1,3-thiazolidin-3-yl]ethyl}benzene-1-sulfonamide (DTEBS) was selected to evaluate glycemia using the glucose tolerance test and insulin secretagogue activity by E.L.I.S.A. The mechanism of action of this compound was studied by 45 Ca2+ influx and whole-cell patch-clamp in rat pancreatic isolated islets...
July 3, 2018: Journal of Cellular Physiology
Kazuno Omori, Hiroshi Nomoto, Akinobu Nakamura, Takahiro Takase, Kyu Yong Cho, Kota Ono, Naoki Manda, Yoshio Kurihara, Shin Aoki, Tatsuya Atsumi, Hideaki Miyoshi
AIMS/INTRODUCTION: Glinides are antidiabetic drugs that enhance the early phase of insulin secretion, but have been considered to be less effective at lowering blood glucose than sulfonylureas. However, glinides possess the lower risk of hypoglycemia and the greater effect on postprandial hyperglycemia, and are particularly recommended for use in elderly patients with type 2 diabetes. We investigated the efficacy and safety of repaglinide compared with sulfonylurea for the treatment of elderly patients...
July 2, 2018: Journal of Diabetes Investigation
Jing-Syuna Ruan, Jie-Kuan Lin, Yi-Ying Kuo, Yun-Wen Chen, Pei-Chun Chen
Lipotoxicity is associated with a high level of fatty acid accumulation in pancreatic β-cells. An overload of free fatty acids contributes to pancreatic β-cell apoptosis and dysfunction. Insulin secretion involves sequential ionic events upon glucose stimulation. ATP sensitive potassium (KATP ) channels serve as glucose sensors and effectively initiate glucose-stimulated insulin secretion. This study investigated the effects of lipotoxicity on the trafficking of KATP channels in pancreatic β cells using chronic palmitic acid -injected mice and treated insulinoma cells...
June 4, 2018: Journal of Nutritional Biochemistry
Yan Xing, Shandong Ye, Yan Chen, Aihong Fan, Zhuohua Xu, Wen Jiang
Introduction:To observe the effects of metformin on urinary excretion of MIF, CD74 and podocalyxin in type 2 diabetics and to explore its possible renoprotective mechanisms. METHODS: 202 uncontrolled type 2 diabetics, who were previously prescribed sulfonylurea monotherapy(n=100) or sulfonylurea in combination with metformin (n=102) were enrolled in the study. The amount of macrophage migration inhibitory factor(MIF) and CD74 in serum, urinary MIF to creatine ratio(UMCR), urinary CD74 to creatine ratio(UCCR), urinary albumin to creatine ratio(UACR) and urinary podocalyxin to creatine ratio (UPCR) were determined...
2018: Endokrynologia Polska
Da Young Lee, Ji Hee Yu, Sanghyun Park, Kyungdo Han, Nam Hoon Kim, Hye Jin Yoo, Kyung Mook Choi, Sei Hyun Baik, Nan Hee Kim, Ji A Seo
This study investigated the effects of diabetes and antidiabetic medications on the risk of pancreatic cancer(PaC). We extracted data on Koreans with newly diagnosed diabetes and selected age- and sex-matched controls provided by the National Health Insurance Corporation. Incident PaC was defined as a new registration in the Korea Central Cancer Registry under ICD-10 C25 with admission history until 2015. During 19,429,617.1 person-years, 8,589 PaCs were identified in 1,005,409 subjects for diabetes group and 4,021,636 subjects for control group...
June 26, 2018: Scientific Reports
Brian M Frier, Wolfgang Landgraf, Mei Zhang, Geremia B Bolli, David R Owens
Patient characteristics associated with hypoglycaemia frequency during insulin glargine 100 U/mL (Gla-100) titration and clinical outcomes at Week 24 were examined using participant-level data from 16 treat-to-target trials of people with type 2 diabetes mellitus inadequately controlled with oral antidiabetes drugs initiating Gla-100 (n=3549). Hypoglycaemia (plasma glucose <3.9 mmol/L or severe) during the first 8 weeks of titration was stratified by number of events (0, 1-3, and ≥4), resulting in 72.5%, 20...
June 25, 2018: Diabetes, Obesity & Metabolism
Sridharan Raghavan, Wenhui G Liu, David R Saxon, Gary K Grunwald, Thomas M Maddox, Jane E B Reusch, Seth A Berkowitz, Liron Caplan
Objective: To determine whether sulfonylurea use, compared with non-sulfonylurea oral diabetes medication use, was associated with 2-year mortality in individuals with well-controlled diabetes and coronary artery disease (CAD). Research design and methods: We studied 5352 US veterans with type 2 diabetes, obstructive CAD on coronary angiography, hemoglobin A1c ≤7.5% at the time of catheterization, and taking zero or one oral diabetes medication (categorized as no medications, non-sulfonylurea medication, or sulfonylurea)...
2018: BMJ Open Diabetes Research & Care
Wei Guo, Lin Nie, Xi-Rui Wang, Mei-Ling Xu, Wen-Jia Yang, Xue-Ying Gao, Xiao-Ling Cai, Li-Nong Ji
Background: Placebo was defined as any therapy that is used for its nonspecific psychological and physiologic effect but has no specific pharmacologic impact on the condition being treated. Besides medication therapies, studies have found that the optimal dietary approach as well as physical activity and education are useful to control hyperglycemia in patients with type 2 diabetes (T2DM). The aim of this study was to evaluate the placebo effects of antidiabetic therapies in Asian and Caucasian T2DM patients and make a comparison between the two ethnicities...
July 5, 2018: Chinese Medical Journal
Sun-Young Park, Eun Jin Jang, Ju-Young Shin, Min-Young Lee, Donguk Kim, Eui-Kyung Lee
OBJECTIVES: This study aimed to identify the prevalence and predictors of hypoglycemia in patients with type 2 diabetes (T2D) using South Korea's nationwide healthcare database. STUDY DESIGN: Retrospective cohort and nested case-control analyses were conducted to estimate the prevalence and predictors of hypoglycemia, respectively. METHODS: A cohort of 2,273,481 patients with T2D was followed to estimate the 1-year prevalence of hypoglycemia...
June 2018: American Journal of Managed Care
Mónika Vörös, László Manczinger, László Kredics, András Szekeres, Kadaikunnan Shine, Naiyf S Alharbi, Jamal M Khaled, Csaba Vágvölgyi
Metal- and pesticide-tolerant biocontrol agents are preferred in integrated pest management, as such strains can be applied in combination with different pesticides. The Bacillus velezensis strain SZMC 6161J proved to be sensitive to copper, nickel, zinc, and cadmium, while manganese elevated its growth. At concentrations higher than 1 mmol L-1 , zinc and iron inhibited the chymotrypsin-like activity of this strain. In addition, trypsin-like protease and palmitoyl esterase activities were insensitive to all tested heavy metals in the applied concentration range...
June 25, 2018: MicrobiologyOpen
Annaswamy Raji, Jianmin Long, Raymond L H Lam, Edward A O'Neill, Samuel S Engel
INTRODUCTION: To assess the efficacy and safety profile of the dipeptidyl-peptidase-4 inhibitor sitagliptin in a population of self-identified Hispanic/Latino patients with type 2 diabetes. METHODS: Data were pooled from ten randomized, double-blind studies in which subjects were treated with sitagliptin 100 mg/day (as mono- or combination therapy) or placebo, and used to evaluate the glycemic efficacy, safety, and tolerability of sitagliptin compared with placebo after 24 weeks of treatment...
June 23, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Jie-Hua Shi, Yan-Yue Lou, Kai-Li Zhou, Dong-Qi Pan
As a sulfonylurea herbicide, sulfosulfuron is extensively applied in controlling broad-leaves and weeds in agriculture. It may cause a potential risk for human and herbivores health due to its widely application and residue in crops and fruits. The study of the binding characteristics of calf thymus DNA (ct-DNA) with sulfosulfuron was performed through a series of spectroscopic techniques and computer simulation. The experimental results showed sulfosulfuron interacted with ct-DNA through the groove binding...
June 18, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Fangfang Zhou, Yangjun Liu, Binbin Yang, Zhiping Hu
The sulfonylurea receptor 1 (SUR1)-regulated NCca-ATP channels were progressively upregulated and demonstrated unchecked opening in central nervous system (CNS) injury, which induced cerebral damage. Glibenclamide (GLI) can block NCca-ATP channels and consequently exert protective effects. Recent studies have found that GLI has antioxidative effects. In this study, we primarily explored the antioxidative effects of GLI in a rat model of intracerebral hemorrhage (ICH). We found that GLI could scavenge free radicals, reduce activated-caspase-3 expression, increase the Bcl-2/Bax ratio, inhibit apoptosis, and improve functional neurological outcomes in a rat model of ICH...
June 19, 2018: Brain Research Bulletin
Richard Silbert, Alejandro Salcido-Montenegro, Rene Rodriguez-Gutierrez, Abdulrahman Katabi, Rozalina G McCoy
PURPOSE OF REVIEW: Hypoglycemia is the most common and often treatment-limiting serious adverse effect of diabetes therapy. Despite being potentially preventable, hypoglycemia in type 2 diabetes incurs substantial personal and societal burden. We review the epidemiology of hypoglycemia in type 2 diabetes, discuss key risk factors, and introduce potential prevention strategies. RECENT FINDINGS: Reported rates of hypoglycemia in type 2 diabetes vary widely as there is marked heterogeneity in how hypoglycemia is defined, measured, and reported...
June 21, 2018: Current Diabetes Reports
May Sanyoura, Louis H Philipson, Rochelle Naylor
PURPOSE OF REVIEW: We provide a review of monogenic diabetes in young children and adolescents with a focus on recognition, management, and pharmacological treatment. RECENT FINDINGS: Monogenic forms of diabetes account for approximately 1-2% of diabetes in children and adolescents, and its incidence has increased in recent years due to greater awareness and wider availability of genetic testing. Monogenic diabetes is due to single gene defects that primarily affect beta cell function with more than 30 different genes reported...
June 22, 2018: Current Diabetes Reports
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