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Novel diabetes therapeutic

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https://www.readbyqxmd.com/read/28812049/importance-of-adiponectin-activity-in-the-pathogenesis-of-alzheimer-s-disease
#1
REVIEW
Masaaki Waragai, Gilbert Ho, Yoshiki Takamatsu, Kazunari Sekiyama, Shuei Sugama, Takato Takenouchi, Eliezer Masliah, Makoto Hashimoto
A recent study suggested that insulin resistance may play a central role in the pathogenesis of Alzheimer's disease (AD). In this regard, it is of note that upregulation of plasma adiponectin (APN), a benign adipokine that sensitizes the insulin receptor signaling pathway and suppresses inflammation, has recently been associated with the severities of amyloid deposits and cognitive deficits in the elderly, suggesting that APN may enhance the risk of AD. These results are unanticipated because AD has been linked to type II diabetes and other metabolic disorders in which hypoadiponectinemia has been firmly established, and because APN ameliorated neuropathological features in a mouse model of neurodegeneration...
August 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28798389/the-mitochondrial-derived-peptides-humanins14g-and-small-humanin-like-peptide-2-exhibit-chaperone-like-activity
#2
Alan K Okada, Kazuki Teranishi, Fleur Lobo, J Mario Isas, Jialin Xiao, Kelvin Yen, Pinchas Cohen, Ralf Langen
Mitochondrial-derived peptides (MDPs) and their analogs have emerged as wide-spectrum, stress response factors protective in amyloid disease models. MDP cytoprotective functions are generally attributed to anti-apoptotic activity, however, little is known about their capacity to facilitate the cell's unfolded protein response via direct interactions with amyloidogenic proteins. Here, we explored the effects of the MDP-analog, humaninS14G (HNG), and the MDP, small humanin-like peptide 2 (SHLP2), on the misfolding of islet amyloid polypeptide (IAPP), a critical pathogenic step in type 2 diabetes mellitus (T2DM)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28774737/the-mechanism-of-diabetic-retinopathy-pathogenesis-unifying-key-lipid-regulators-sirtuin-1-and-liver-x-receptor
#3
Sandra S Hammer, Eleni Beli, Nermin Kady, Qi Wang, Kiana Wood, Todd A Lydic, Goldis Malek, Daniel R Saban, Xiaoxin X Wang, Sugata Hazra, Moshe Levi, Julia V Busik, Maria B Grant
Diabetic retinopathy (DR) is a complication secondary to diabetes and is the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to be realized. Several clinical trials have highlighted the vital role dyslipidemia plays in the progression of DR. Additionally, it has recently been shown that activation of Liver X receptor (LXRα/LXRβ) prevents DR in diabetic animal models. LXRs are nuclear receptors that play key roles in regulating cholesterol metabolism, fatty acid metabolism and inflammation...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28772216/minocycline-attenuates-the-development-of-diabetic-neuropathy-by-inhibiting-spinal-cord-notch-signaling-in-rat
#4
Cheng Yang, Jie Gao, Banglin Wu, Nuo Yan, Hui Li, Yiqing Ren, Yufei Kan, Jiamin Liang, Yang Jiao, Yonghao Yu
We studied the effects of minocycline (an inhibitor of microglial activation) on the expression and activity of Notch-1 receptor, and explored the therapeutic efficacy of minocycline combined with Notch inhibitor DAPT in the treatment of diabetic neuropathic pain (DNP). Diabetic rat model was established by intraperitoneal injection (ip) of Streptozotocin (STZ). Expression and activity of Notch-1 and expression of macrophage/microglia marker Iba-1 were detected by WB. Diabetes induction significantly attenuated sciatic nerve conduction velocity, and dramatically augmented the expression and the activity of Notch-1 in the lumbar enlargement of the spinal cord...
July 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28770533/hyperuricemia-type-2-diabetes-mellitus-and-hypertension-an-emerging-association
#5
REVIEW
Ibrahim Mortada
Uric acid is the final oxidation product of purine metabolism in circulation and has been associated with the occurrence of gout and kidney stones. Type 2 diabetes mellitus and hypertension are two important public health challenges, and both are linked to increased risk of cardiovascular events. Hyperuricemia has recently emerged as an independent risk factor in the development of type 2 diabetes mellitus and hypertension through several proposed mechanisms. Few clinical trials investigated the use of uric acid lowering agents in the management of these two disease entities; however, their results provided encouraging evidence to a potential role for these agents in fighting disease burden...
September 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28770317/mitochondrial-h-atp-synthase-in-human-skeletal-muscle-contribution-to-dyslipidaemia-and-insulin-resistance
#6
Laura Formentini, Alexander J Ryan, Manuel Gálvez-Santisteban, Leslie Carter, Pam Taub, John D Lapek, David J Gonzalez, Francisco Villarreal, Theodore P Ciaraldi, José M Cuezva, Robert R Henry
AIMS/HYPOTHESIS: Mitochondria are important regulators of the metabolic phenotype in type 2 diabetes. A key factor in mitochondrial physiology is the H(+)-ATP synthase. The expression and activity of its physiological inhibitor, ATPase inhibitory factor 1 (IF1), controls tissue homeostasis, metabolic reprogramming and signalling. We aimed to characterise the putative role of IF1 in mediating skeletal muscle metabolism in obesity and diabetes. METHODS: We examined the 'mitochondrial signature' of obesity and type 2 diabetes in a cohort of 100 metabolically characterised human skeletal muscle biopsy samples...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28770170/high-throughput-microplate-based-assay-to-monitor-plasma-membrane-wounding-and-repair
#7
Sarika Pathak-Sharma, Xiaoli Zhang, Jonathan G T Lam, Noah Weisleder, Stephanie M Seveau
The plasma membrane of mammalian cells is susceptible to disruption by mechanical and biochemical damages that frequently occur within tissues. Therefore, efficient and rapid repair of the plasma membrane is essential for maintaining cellular homeostasis and survival. Excessive damage of the plasma membrane and defects in its repair are associated with pathological conditions such as infections, muscular dystrophy, heart failure, diabetes, and lung and neurodegenerative diseases. The molecular events that remodel the plasma membrane during its repair remain poorly understood...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28769873/targeting-obesity-and-diabetes-to-treat-heart-failure-with-preserved-ejection-fraction
#8
REVIEW
Raffaele Altara, Mauro Giordano, Einar S Nordén, Alessandro Cataliotti, Mazen Kurdi, Saeed N Bajestani, George W Booz
Heart failure with preserved ejection fraction (HFpEF) is a major unmet medical need that is characterized by the presence of multiple cardiovascular and non-cardiovascular comorbidities. Foremost among these comorbidities are obesity and diabetes, which are not only risk factors for the development of HFpEF, but worsen symptoms and outcome. Coronary microvascular inflammation with endothelial dysfunction is a common denominator among HFpEF, obesity, and diabetes that likely explains at least in part the etiology of HFpEF and its synergistic relationship with obesity and diabetes...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28769000/a-novel-bongkrekic-acid-analog-mediated-modulation-of-the-size-of-lipid-droplets-evidence-for-the-appearance-of-smaller-adipocytes
#9
Hiroyuki Okazaki, Shuso Takeda, Hiroyuki Ishii, Yukimi Takemoto, Satoshi Fujita, Masaki Suyama, Kenji Matsumoto, Mitsuru Shindo, Hironori Aramaki
Thiazolidinediones (TZDs) are known as peroxisome proliferator-activated receptor γ (PPARγ) activators, and are used in the treatment of diabetes. Although the usefulness of TZDs has been demonstrated, some of their side effects are becoming an obstacle to their clinical applicability; edema is known to be evoked by the "structural characteristics" of TZD, but not by the PPARγ activation. Thus, novel therapeutic modalities (i.e., non-TZD-type PPARγ activators) having different structures to those of TZDs are desired...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28768770/nmda-receptors-mediate-leptin-signaling-and-regulate-potassium-channel-trafficking-in-pancreatic-%C3%AE-cells
#10
Yi Wu, Dale A Fortin, Veronica A Cochrane, Pei-Chun Chen, Show-Ling Shyng
NMDA receptors (NMDARs) are Ca2+-permeant, ligand-gated ion channels activated by the excitatory neurotransmitter glutamate and have well-characterized roles in the nervous system. The expression and function of NMDARs in pancreatic β cells, by contrast, are poorly understood. Here, we report a novel function of NMDARs in β-cells. Using a combination of biochemistry, electrophysiology, and imaging techniques we now show that NMDARs have a key role in mediating the effect of leptin to modulate β-cell electrical activity by promoting AMP-activated protein kinase (AMPK)-dependent trafficking of KATP and Kv2...
August 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28767442/hydrogen-sulfide-ameliorates-cognitive-dysfunction-in-streptozotocin-induced-diabetic-rats-involving-suppression-in-hippocampal-endoplasmic-reticulum-stress
#11
Wei Zou, Juan Yuan, Zhuo-Jun Tang, Hai-Jun Wei, Wei-Wen Zhu, Ping Zhang, Hong-Feng Gu, Chun-Yan Wang, Xiao-Qing Tang
Diabetes induces impairment in cognitive function. There is substantial evidence that hippocampal endoplasmic reticulum (ER) stress is involved in diabetic cognitive impairment. Hydrogen sulfide (H2S) attenuates the learning and memory decline in experimental Alzheimer's disease and inhibits the hippocampal ER stress in homocysteine-exposed rats. Therefore, this aim of the present work was to investigate whether H2S ameliorates the diabetic cognitive dysfunction involving inhibition of hippocampal ER stress...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28765812/role-of-ampd2-in-impaired-glucose-tolerance-induced-by-high-fructose-diet
#12
Athanasius Wrin Hudoyo, Tetsuaki Hirase, Andreas Tandelillin, Masahiko Honda, Manabu Shirai, Jidong Cheng, Hiroko Morisaki, Takayuki Morisaki
A high intake of products containing fructose is known to mediate insulin resistance. In the liver, AMPD2, an isoform of AMPD, has important glucose metabolic homeostasis functions including maintenance of AMP-activated protein kinase (AMPK). We speculated that AMPD2 induces impaired glucose tolerance in individuals who consume a high-fructose diet. We gave either a normal-chow (NCD) or high-fructose (HFrD) diet for 40 days to 8-week-old male wild-type (WT) and Ampd2 -/- homozygote (A2 -/-) C57BL/6 mice...
December 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28762104/ngf-attenuates-high-glucose-induced-er-stress-preventing-schwann-cell-apoptosis-by-activating-the-pi3k-akt-gsk3%C3%AE-and-erk1-2-pathways
#13
Rui Li, Yanqing Wu, Shuang Zou, Xiaofang Wang, Yiyang Li, Ke Xu, Fanghua Gong, Yanlong Liu, Jian Wang, Yi Liao, Xiaokun Li, Jian Xiao
Diabetic peripheral neuropathy (DPN) is one of the most common and troublesome complications of diabetes mellitus. It has been demonstrated that nerve growth factor (NGF) exerts a pivotal role in the regulation of neuronal growth and the promotion of DPN recovery. However, the exact molecular mechanisms are not well understood. Recent studies have indicated that as a novel therapeutic target, endoplasmic reticulum (ER) stress participates in the onset and progression of DPN. In the present study, it has been demonstrated that NGF prevents the sciatic nerve from degeneration and demyelination in DPN rats...
July 31, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28759754/potential-of-the-chlorogenic-acid-as-multitarget-agent-insulin-secretagogue-and-ppar-%C3%AE-%C3%AE-dual-agonist
#14
Maetzin Becerra Sanchez, Elizabeth Miranda-Perez, Juan Carlos Gomez Verjan, Maria de Los Angeles Fortis Barrera, Julia Perez-Ramos, Francisco Javier Alarcon-Aguilar
The chlorogenic acid (CGA) is a natural product isolated from Cecropia obtusifolia, which possesses several pharmacological properties, such as: anti-carcinogenic, neuroprotective, antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic. In relation to its effects on the hyperglycemia and hypertriglyceridemia, few is known about the mechanisms in which this compound may be acting, therefore, the aim of the present study was to determine if CGA acts as an insulin secretagogue increasing intracellular calcium concentrations ([Ca(2+)]i) in RINm5F cells; or as an insulin sensitizer and lipid-lowering agent stimulating the expression of PPARγ and PPARα, respectively, in 3T3-L1 adipocytes...
July 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28755444/bolusing-frequency-and-amount-impacts-glucose-control-during-hybrid-closed-loop
#15
L Bally, H Thabit, Y Ruan, J K Mader, H Kojzar, S Dellweg, C Benesch, S Hartnell, L Leelarathna, M E Willinska, M L Evans, S Arnolds, T R Pieber, R Hovorka
AIM: To compare bolus insulin delivery patterns during closed-loop home studies in adults with suboptimally [HbA1c 58-86 mmol/mol (7.5%-10%)] and well-controlled [58 mmol/mol (< 7.5%)] Type 1 diabetes. METHODS: Retrospective analysis of daytime and night-time insulin delivery during home use of closed-loop over 4 weeks. Daytime and night-time controller effort, defined as amount of insulin delivered by closed-loop relative to usual basal insulin delivery, and daytime bolus effort, defined as total bolus insulin delivery relative to total daytime insulin delivery were compared between both cohorts...
July 29, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28754350/beneficial-metabolic-effects-of-dietary-epigallocatechin-gallate-alone-and-in-combination-with-exendin-4-in-high-fat-diabetic-mice
#16
Nupur M Pathak, Paul J B Millar, Varun Pathak, Peter R Flatt, Victor A Gault
OBJECTIVE: Significant attempts are being made to generate multifunctional, hybrid or peptide combinations as novel therapeutic strategies for type 2 diabetes, however this presents key challenges including design and pharmaceutical development. In this study, we evaluated metabolic properties of oral nutritional supplement epigallocatechin gallate (EGCG) in combination with GLP-1 agonist exendin-4 in a mouse model of dietary-induced diabetes and obesity. METHODS: EGCG, exendin-4 or combination of both were administered twice-daily over 28 days to high fat (HF) mice on background of low-dose streptozotocin...
July 25, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28753062/long-noncoding-rna-h19-acts-as-a-competing-endogenous-rna-to-mediate-ctgf-expression-by-sponging-mir-455-in-cardiac-fibrosis
#17
Zhi-Wen Huang, Li-Hong Tian, Bin Yang, Run-Min Guo
Cardiac fibrosis is closely related to multiple cardiovascular system diseases, and noncoding RNAs (ncRNAs), including long noncoding RNA (lncRNA) and microRNA (miRNA), have been reported to play a vital role in fibrogenesis. The present study aims to investigate the potential regulatory mechanism of lncRNA H19 and miR-455 on fibrosis-associated protein synthesis in cardiac fibroblasts (CFs). miRNA microarray assay revealed 34 significantly dysregulated miRNAs, including 13 upregulated miRNAs and 21 downregulated miRNAs...
July 28, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28752417/metformin-alleviated-the-neuronal-oxidative-stress-in-hippocampus-of-rats-under-single-prolonged-stress
#18
Jiangang Wang, Bing Xiao, Fang Han, Yuxiu Shi
In an animal model of post-traumatic stress disorder (PTSD), our previous studies showed mitochondrial stress-induced apoptosis in the hippocampus. Metformin, the most commonly prescribed anti-diabetic drug, exerts its effects through 5'-adenosine monophosphate-activated protein kinase (AMPK) activation. It was shown that a neuroprotective role was gradually established against stroke, spinal cord injury and Parkinson's disease. The aim of this study was to explore the role of the AMPK pathway in neuronal apoptosis in the hippocampus using a rat model of PTSD...
July 27, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28752048/myeloid-protein-tyrosine-phosphatase-1b-ptp1b-deficiency-protects-against-atherosclerotic-plaque-formation-in-the-apoe-mouse-model-of-atherosclerosis-with-alterations-in-il10-ampk%C3%AE-pathway
#19
D Thompson, N Morrice, L Grant, S Le Sommer, K Ziegler, P Whitfield, N Mody, H M Wilson, M Delibegović
OBJECTIVE: Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with Type 1 or Type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance due to impaired insulin receptor (IR) signaling. Moreover, inflammatory cells, in particular macrophages, play a key role in pathogenesis of atherosclerosis and insulin resistance in humans. We hypothesized that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR, specifically in macrophages, would have beneficial anti-inflammatory effects and lead to protection against atherosclerosis and CVD...
August 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28750203/synthesis-%C3%AE-glucosidase-inhibitory-activity-and-in-silico-study-of-tris-indole-hybrid-scaffold-with-oxadiazole-ring-as-potential-leads-for-the-management-of-type-ii-diabetes-mellitus
#20
Muhammad Taha, Fazal Rahim, Syahrul Imran, Nor Hadiani Ismail, Hayat Ullah, Manikandan Selvaraj, Muhammad Tariq Javid, Uzma Salar, Muhammad Ali, Khalid Mohammed Khan
Discovery of α-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of type-II diabetes mellitus and the other carbohydrate mediated disease. In continuation of our drug discovery research on potential antidiabetic agents, we synthesized novel tris-indole-oxadiazole hybrid analogs (1-21), structurally characterized by various spectroscopic techniques such as (1)H NMR, EI-MS, and (13)C NMR. Elemental analysis was found in agreement with the calculated values...
July 18, 2017: Bioorganic Chemistry
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