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Nicotinamide AND diabetes

Zhiyi Liu, Dimitra Pouli, Carlo A Alonzo, Antonio Varone, Sevasti Karaliota, Kyle P Quinn, Karl Münger, Katia P Karalis, Irene Georgakoudi
Monitoring subcellular functional and structural changes associated with metabolism is essential for understanding healthy tissue development and the progression of numerous diseases, including cancer, diabetes, and cardiovascular and neurodegenerative disorders. Unfortunately, established methods for this purpose either are destructive or require the use of exogenous agents. Recent work has highlighted the potential of endogenous two-photon excited fluorescence (TPEF) as a method to monitor subtle metabolic changes; however, mechanistic understanding of the connections between the detected optical signal and the underlying metabolic pathways has been lacking...
March 2018: Science Advances
George Cătălin Marinescu, Roua-Gabriela Popescu, Anca Dinischiotu
Over 12% of the world's health resources are spent on treating diabetes, as high blood glucose is the third cause of mortality worldwide. Insulin resistance is the basis of the most common form of diabetes: type 2 diabetes. Recent animal studies report successful attempts at reversing type 2 diabetes by the administering of the NAD+ precursor nicotinamide mononucleotide (NMN). However, the current high price of this molecule urges for more efficient and cost-effective production methods. This work proposes a method for purifying NMN by Size Exclusion Chromatography (SEC) on silica with a covalently attached coating of poly(2-hydroxyethyl aspartamide) (PolyHEA) stationary phase using an isocratic elution with a denaturing mobile phase (50 mM formic acid) from a complex molecular mixture such as a fermentation broth...
March 13, 2018: Scientific Reports
Gui Pan, Haojie Hao, Jianping Liu
The transplantation of insulin-producing cells (IPCs) or pancreatic progenitor cells is a theoretical therapy for diabetes with insulin insufficiency. Isolated hepatocytes from newborn rats (within 24 h after birth) were progressively induced into IPCs using 5-aza-2'-deoxycytidine, Trichostatin A, retinoic acid, insulin-transferrin-selenium, and nicotinamide. We transplanted Pdx1+ pancreatic progenitors into STZ-induced diabetic mice and found the decreased blood glucose and increased insulin level in comparison with diabetic model...
March 7, 2018: Biochemical and Biophysical Research Communications
Hlaing H Maw, Xingzhong Zeng, Scot Campbell, Mitchell E Taub, Aaron M Teitelbaum
BI 187004, an 11β-hydroxysteroid dehydrogenase 1 (HSD) inhibitor, was administered once daily for 14 days to eight patients with type 2 diabetes mellitus. N-methylation was identified as a major biotransformation pathway. In four patients treated with BI 187004, the plasma exposure of an N-methylbenzimidazole metabolite (M1) was 7 fold higher than the remaining four patients, indicating a substantial degree of metabolic variation. To identify the methyltransferase enzyme(s) responsible for N-methylation, BI 187004 was incubated with human liver microsomes (HLM), human kidney microsomes (HKM), and their respective cytosolic preparations in the presence and absence of isoform-selective chemical inhibitors...
March 7, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
D Canistro, F Vivarelli, S Cirillo, A Soleti, B Albertini, N Passerini, G Merizzi, M Paolini
PURPOSE: We previously showed the positive effects of the new antioxidant molecule bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) in reducing basal hyperglycaemia and relieving glucose intolerance in a diabetes model. However, the chemical properties of IAC did not allow an efficient oral administration, thus representing the main failing of that study. Here, we tested the effect of a new oral delivery system based on solid lipid microparticles (SLMs) in a diabetes mouse model...
March 6, 2018: Journal of Endocrinological Investigation
Nobutomo Ikarashi, Takahiro Toda, Yusuke Hatakeyama, Yoshiki Kusunoki, Risako Kon, Nanaho Mizukami, Miho Kaneko, Sosuke Ogawa, Kiyoshi Sugiyama
We have previously demonstrated that acacia polyphenol (AP) exerts strong anti-obesity, anti-diabetic, and anti-atopic dermatitis effects. In the present study, we investigated the anti-hypertensive effects of AP. Spontaneously hypertensive rats (SHR) with hypertension and control Wistar Kyoto rats (WKY) were used. WKY and SHR were fed AP-containing food or AP-free food (control group) ad libitum for 4 weeks, and their blood pressures were measured. After AP administration, both systolic and diastolic blood pressures were significantly lower in the SHR group than in the control group...
March 1, 2018: International Journal of Molecular Sciences
Pin-Chun Chao, Yingxiao Li, Chin-Hong Chang, Ja Ping Shieh, Juei-Tang Cheng, Kai-Chun Cheng
Animal models are widely used to develop drugs for treating diabetes mellitus (DM). Insulin resistance (IR) is one of the main problems in type-2 DM (T2DM). Streptozotocin (STZ) is used to damage pancreatic cells for induction of DM. Many rat models were applied in research as T2DM. However, the degree of IR in each model is unknown. In the present study, IR and insulin signaling were compared in four models of type 2 diabetes: rats fed a fructose-rich chow for 8 weeks, rats feed high-fat chow for 4 weeks followed by injection with streptozotocin (35 mg/kg, i...
February 24, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Aimo Kannt, Sridharan Rajagopal, Sanjay Venkatachalapathi Kadnur, Juluri Suresh, Ravi Kanth Bhamidipati, Srinivasan Swaminathan, Mahanandeesha Siddappa Hallur, Rajendra Kristam, Ralf Elvert, Jörg Czech, Anja Pfenninger, Christine Rudolph, Herman Schreuder, Devaraj Venkatapura Chandrasekar, Vishal Subhash Mane, Swarnakumari Birudukota, Shama Shaik, Bharat Ravindra Zope, Raghunadha Reddy Burri, Niranjan Naranapura Anand, Manish Kumar Thakur, Manvi Singh, Reejuana Parveen, Saravanan Kandan, Ramesh Mullangi, Takeshi Yura, Ramachandraiah Gosu, Sven Ruf, Saravanakumar Dhakshinamoorthy
Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that catalyzes the transfer of a methyl group from the co-factor S-adenosyl-L-methionine (SAM) onto the substrate, nicotinamide (NA) to form 1-methyl-nicotinamide (MNA). Higher NNMT expression and MNA concentrations have been associated with obesity and type-2 diabetes. Here we report a small molecule analog of NA, JBSNF-000088, that inhibits NNMT activity, reduces MNA levels and drives insulin sensitization, glucose modulation and body weight reduction in animal models of metabolic disease...
February 26, 2018: Scientific Reports
Nejat Kheiripour, Jamshid Karimi, Iraj Khodadadi, Heidar Tavilani, Mohammad Taghi Goodarzi, Mohammad Hashemnia
BACKGROUND: In this study, we have investigated whether silymarin intake influences lipid and glycogen content in conjunction with sirtuin1 (SIRT1) and sterol regulatory element-binding protein 1c (SREBP-1c) expressions in liver of type 2 diabetic rat. METHODS: Thirty-six male Wistar rats were randomly divided into six groups: control groups (C) and diabetic groups (D); the control groups received 60 or 120 mg/kg silymarin (C+S60 or C+S120), and the diabetic groups received 60 or 120 mg/kg silymarin (D+S60 or D+S120) daily for 8 weeks...
February 24, 2018: Journal of Basic and Clinical Physiology and Pharmacology
Kuo-Ping Shen, Hui-Li Lin, Hsueh-Wei Yen, Su-Ling Hsieh, Li-Mei An, Bin-Nan Wu
This study examined the effects of eugenosedin-A (Eu-A) in a streptozotocin (STZ)/nicotinamide-induced rat model of type II diabetes mellitus (T2DM). Six-week-old Sprague-Dawley rats were randomly divided into three groups: (1) RD group, normal rats fed a regular diet (RD), (2) DM group, T2DM rats fed a high-fat diet, and (3) Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day). After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group...
March 2018: Kaohsiung Journal of Medical Sciences
Hanae Naceiri Mrabti, Karima Sayah, Nidal Jaradat, Faouzi Kichou, Abdelaziz Ed-Dra, Badiaa Belarj, Yahia Cherrah, My El Abbes Faouzi
Background Diabetes mellitus (DM) is currently a major health problem and the most common chronic disease worldwide. Traditional medicinal plants remedies remain a potential adjunct therapy to maintain better glycemic control while also imparting few side-effects. Arbutus unedo L. has been traditionally used to manage several diseases including diabetes. This study was undertaken to contribute the validation of the traditional use of Arbutus unedoL. (Ericaceae) in the treatment of diabetes. Methods In-vitro antidiabetic effect of the A...
February 21, 2018: Journal of Complementary & Integrative Medicine
S V Kotov, E V Isakova, V Yu Leidvoll, Yu A Belova, T V Volchenkova, A V Borodin, V A Shvedov
AIM: To study the efficacy of the complex therapy, including cocarnit (group B vitamins, triphosadenine and nicotinamide), of diabetic neuropathy. MATERIAL AND METHODS: Forty-one patients with diabetes mellitus type 2 and distal symmetric sensorimotor polyneuropathy were examined. Patients were divided into 2 groups. Patients of the main group (n=26) received complex therapy, including cocarnit, and patients of the comparison group (n=15) received standard treatment...
2018: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Ayodele Olufemi Morakinyo, Titilola Aderonke Samuel, Daniel Abiodun Adekunbi
OBJECTIVE: We investigated the effects of magnesium supplementation on glucose tolerance, insulin sensitivity, oxidative stress as well as the concentration of insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide induced type-2 diabetic (T2D) rats. METHODS: Rats were divided into four groups designated as: 1) control (CTR); 2) diabetic untreated (DU); 3) diabetic treated with 1 mg of Mg/kg diet (Mg1-D); and 4) diabetic treated with 2 mg of Mg/kg diet (Mg2-D)...
January 1, 2018: Endocrine Regulations
Wale Johnson Adeyemi, Luqman Aribidesi Olayaki
Because optimising therapy for the management of diabetes mellitus remains challenging, the study investigated the effects of salmon calcitonin (Sct) and/or omega-3 fatty acids (N-3 - eicosapentaenoic acid and docosahexaenoic acid-3:2), compared to metformin, on selected biochemical parameters in male Wistar rats, in an experimental model of diabetes. Forty rats were used for this study. They were divided into eight groups of five rats each, which included: Normal control; Diabetic (D) control; D + N-3; D + low dose Sct (Sct...
February 9, 2018: Pathophysiology: the Official Journal of the International Society for Pathophysiology
Sven Ruf, Mahanandeesha Siddappa Hallur, Nisha K Anchan, Indu N Swamy, Karthikai Raj Murugesan, Sayantani Sarkar, Lokesh Kananti Narasimhulu, V P Rama Kishore Putta, Shama Shaik, Devaraj Venkatapura Chandrasekar, Vishal Subhash Mane, Sanjay Venkatachalapathi Kadnur, Juluri Suresh, Ravi Kanth Bhamidipati, Manvi Singh, Raghunadha Reddy Burri, Rajendra Kristam, Herman Schreuder, Joerg Czech, Christine Rudolph, Alexander Marker, Thomas Langer, Ramesh Mullangi, Takeshi Yura, Ramachandraiah Gosu, Aimo Kannt, Saravanakumar Dhakshinamoorthy, Sridharan Rajagopal
Nicotinamide N-methyltransferase (NNMT) has been linked to obesity and diabetes. We have identified a novel nicotinamide (NA) analog, compound 12 that inhibited NNMT enzymatic activity and reduced the formation of 1-methyl-nicotinamide (MNA), the primary metabolite of NA by ∼80% at 2 h when dosed in mice orally at 50 mg/kg.
January 31, 2018: Bioorganic & Medicinal Chemistry Letters
Ruma Rani, Shakti Dahiya, Dinesh Dhingra, Neeraj Dilbaghi, Ki-Hyun Kim, Sandeep Kumar
Thymoquinone is abioactive constituent of Nigella sativa seeds. It has been reported to possess antihyperglycemic effect in rats. However, the effect of nanoformulation (NF) of thymoquinone has not been reported in literature. So, the present study was designed with the aim to investigate the effect of nanoformulation of thymoquinone in streptozotocin-nicotinamide induced type-2 diabetic rats and compare its effect with pure bioactive compound as well as metformin, a standard antidiabetic drug. It is the first study reporting the use of thymoquinone NF against diabetes...
February 5, 2018: Chemico-biological Interactions
Alamzeb Khan, Hazem Dawoud, Tadeusz Malinski
Background: Clinical studies indicate that vitamin D3 improves circulation and may have beneficial effects in hypertension. This study uses nanomedical systems to investigate the role of 1,25-dihydroxy vitamin D3 in the preservation/restoration of endothelial function in an angiotensin II (Ang II) cellular model of hypertension. Methods: 1,25-dihydroxy vitamin D3-stimulated nitric oxide (NO) and peroxynitrite (ONOO-) concentrations were measured in situ with nanosensors (200-300 mm diameter with a detection limit of 1 nM) in human umbilical vein endothelial cells of African American (AA) and Caucasian American (CA) donors exposed to Ang II...
2018: International Journal of Nanomedicine
Devy Deliyanti, Saeed F Alrashdi, Sih Min Tan, Colin Meyer, Keith W Ward, Judy B de Haan, Jennifer L Wilkinson-Berka
Purpose: Oxidative stress is a causal factor in the development of diabetic retinopathy; however, clinically relevant strategies to treat the disease by augmenting antioxidant defense mechanisms have not been fully explored. We hypothesized that boosting nuclear factor erythroid-2-related factor 2 (Nrf2) antioxidant capacity with the novel Nrf2 activator dh404, would protect the retina in diabetes including vision-threatening breakdown of the blood-retinal barrier (BRB) and associated damage to macroglial Müller cells...
February 1, 2018: Investigative Ophthalmology & Visual Science
Atsuo Tahara, Toshiyuki Takasu
Diabetic nephropathy is the leading cause of end-stage renal disease and is associated with high-cardiovascular risk and significant morbidity and mortality. The recent development of sodium-glucose cotransporter (SGLT) 2 inhibitors offers a new antidiabetic therapy via enhanced glucose excretion; however, the beneficial effect of these drugs on the development of type 2 diabetic overt nephropathy is still largely unclear. We examined the therapeutic effects of the SGLT2 inhibitor ipragliflozin on various diabetic symptoms and the progression of nephropathy in uninephrectomized type 2 diabetic mice, which exhibit not only typical diabetic symptoms, such as impaired insulin secretion, glucose intolerance, hyperglycemia, and obesity, but also overt nephropathy with decline in renal function...
January 26, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Yan Cui, Yan Shi, Yan Bao, Shulong Wang, Qiuju Hua, Yun Liu
Diabetes affects a large proportion of population wide across the world and kidney is a main target organ of diabetic complications. Zingerone is a stable active component derived from dry ginger rhizome. We investigated the effect of zingerone on diabetic nephropathy and explored the possible mechanisms. We showed that zingerone decreased the levels of serum insulin, C-peptide and glycosylated hemoglobin A1c. The levels of blood urea nitrogen (BUN), serum creatinine, urinary albumin content and albumin/creatinine ratio (ACR) were reduced by zingerone...
January 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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