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insulin analog

Sudha S Shankar, R Ravi Shankar, Lori A Mixson, Deborah L Miller, Barnali Pramanik, Amy K O'Dowd, Donna M Williams, Clay B Frederick, Chan R Beals, S Aubrey Stoch, Helmut O Steinberg, David E Kelley
Oxyntomodulin (OXM), an enteroendocrine hormone, causes appetite suppression, increased energy expenditure, and weight loss in obese humans via activation of GLP-1 and glucagon receptors. However, the effects of OXM on glucose homeostasis remain ill-defined. To address this gap, we evaluated the effects of an intravenous (IV) infusion of native OXM on insulin secretory rates (ISR) and glycemic excursion in a graded glucose infusion (GGI) procedure in two separate randomized, placebo-controlled, single dose crossover trials in 12 overweight and obese subjects without diabetes, and in 12 obese subjects with Type 2 diabetes (T2DM) respectively, using the GLP-1 analog, liraglutide as a comparator in the T2DM...
March 15, 2018: Diabetes
O M Selivanova, S Yu Grishin, A V Glyakina, A S Sadgyan, N I Ushakova, O V Galzitskaya
We analyzed the structural properties of the peptide hormone insulin and described the mechanism of its physiological action, as well as effects of insulin in type 1 and 2 diabetes. Recently published data on the development of novel insulin preparations based on combining molecular design and genetic engineering approaches are presented. New strategies for creation of long-acting insulin analogs, the mechanisms of functioning of these analogs and their structure are discussed. Side effects of insulin preparations are described, including amyloidogenesis and possible mitogenic effect...
January 2018: Biochemistry. Biokhimii︠a︡
Mary Courtney Moore, David E Kelley, Raul C Camacho, Peter Zafian, Tian Ye, Songnian Lin, Niels C Kaarsholm, Ravi Nargund, Terri M Kelly, Margaret Van Heek, Stephen F Previs, Christopher Moyes, Marta S Smith, Ben Farmer, Phil Williams, Alan D Cherrington
We evaluated the hepatic and nonhepatic responses to glucose-responsive insulin (GRI). Eight dogs received GRI or regular human insulin (HI) in random order. A primed, continuous intravenous infusion of [3-3 H]glucose began at -120 min. Basal sampling (-30 to 0 min) was followed by 2 study periods (150 min each), P1 and P2. At 0 min, somatostatin and GRI (36±3 pmol/kg/min) or HI (1.8 pmol/kg/min) were infused IV; basal glucagon was replaced intraportally. Glucose was infused intravenously to clamp plasma glucose at 80 mg/dL (P1) and 240 mg/dL (P2)...
March 14, 2018: Diabetes
Tandra R Chakraborty, Victoria Gomez, Debasis Adhikari, Sanjoy Chakraborty
OBJECTIVE: To determine the hormonal changes that occur as a result of the long-term intake of a very-high-fat diet (VHFD) that leads to simultaneous changes in the islets of Langerhans and adipocyte cell size. METHODS: Male mice were fed with a normal chow diet (ND, n = 15) and a VHFD (n = 30) for 2, 12, and 24 weeks. Body weight, food intake, caloric intake (fat [saturated and unsaturated], protein, and carbohydrate), hormone levels (leptin and insulin), and islet of Langerhans/adipocyte size were quantitatively recorded...
March 13, 2018: Journal of the American College of Nutrition
William J Valentine, Kate Van Brunt, Kristina S Boye, Richard F Pollock
OBJECTIVE: The aim of the present study was to evaluate the cost effectiveness of rapid-acting analog insulin relative to regular human insulin in adults with type 1 diabetes mellitus in Germany. METHODS: The PRIME Diabetes Model, a patient-level, discrete event simulation model, was used to project long-term clinical and cost outcomes for patients with type 1 diabetes from the perspective of a German healthcare payer. Simulated patients had a mean age of 21.5 years, duration of diabetes of 8...
March 10, 2018: Applied Health Economics and Health Policy
Jeremy Streuli, Alan G Harris, Cecilia Cottiny, Florent Allagnat, Adrian F Daly, Eric Grouzmann, Karim Abid
BACKGROUND: Somatostatin analogs (SSAs) are first-line medical therapy for the treatment of acromegaly and neuroendocrine tumors that express somatostatin receptors (SSTR). Somatostatin suppresses secretion of a large number of hormones through the stimulation of the five SSTR. However, unbalanced inhibition of secretion as observed with the highly potent SSAs pasireotide causes hyperglycaemia mainly by inhibiting insulin secretion. In contrast, AP102 a new SSAs has neutral effect on blood glucose while suppressing GH secretion...
March 2, 2018: Neuropeptides
Sarah Morar Schneider, Vidya Sridhar, Amanda K Bettis, Heather Heath-Barnett, Cynthia J Balog-Alvarez, Lee-Jae Guo, Rachel Johnson, Scott Jaques, Stanislav Vitha, Alan C Glowcwski, Joe N Kornegay, Peter P Nghiem
PURPOSE: Metabolic dysfunction in Duchenne muscular dystrophy (DMD) is characterized by reduced glycolytic and oxidative enzymes, decreased and abnormal mitochondria, decreased ATP, and increased oxidative stress. We analyzed glucose metabolism as a potential disease biomarker in the genetically homologous golden retriever muscular dystrophy (GRMD) dog with molecular, biochemical, and in vivo imaging. PROCEDURES: Pelvic limb skeletal muscle and left ventricle tissue from the heart were analyzed by mRNA profiling, qPCR, western blotting, and immunofluorescence microscopy for the primary glucose transporter (GLUT4)...
March 5, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Zhongjie Fu, Zhongxiao Wang, Chi-Hsiu Liu, Yan Gong, Bertan Cakir, Raffael Liegl, Ye Sun, Steven S Meng, Samuel B Burnim, Ivana Arellano, Elizabeth Moran, Rubi Duran, Alexander Poblete, Steve S Cho, Saswata Talukdar, James D Akula, Ann Hellström, Lois E H Smith
Retinal neuronal abnormalities occur before vascular changes in diabetic retinopathy. Accumulating experimental evidence suggests that neurons control vascular pathology in diabetic and other neovascular retinal disease. Therefore, normalizing neuronal activity in diabetes may prevent vascular pathology. We investigated whether fibroblast growth factor 21 (FGF21) prevented retinal neuronal dysfunction in insulin-deficient diabetic mice. We found that in diabetic neural retina, photoreceptor rather than inner retinal function was most affected and administration of the long-acting FGF21 analog, PF-05231023 restored the retinal neuronal functional deficits detected by electroretinography...
February 27, 2018: Diabetes
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
Yeong-Min Yoo, Yung Chul Park
Streptozotocin (STZ), a glucose analog, induces diabetes in experimental animals by inducing preferential cytotoxicity in pancreatic beta cells. We investigated whether STZ reduced the production of intracellular insulin through autophagy in insulinoma INS-1E cells. Typically, 2 mM STZ treatment for 24 h significantly decreased cell survival. STZ treatment led to significant decrease in phospho-AMP-activated protein kinase (p-AMPK) level; reduction in levels of phospho-protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1α (IRE1α); significant reduction in levels of p85α, p110, phospho-serine and threonine kinase/protein kinase B (p-Akt/PKB) (Ser473), phospho-extracellular-regulated kinase (p-ERK), and phospho-mammalian target of rapamycin (p-mTOR); increase in levels of Cu/Zn-superoxide dismutase (SOD), Mn-SOD, and catalase; decrease in B-cell lymphoma 2 (Bcl-2) expression; increase in Bcl-2-associated X protein (Bax) expression; increase in levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1; and reduction in production of intracellular insulin...
February 27, 2018: DNA and Cell Biology
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
Yue Gao, Ke Wang, Yun Chen, Li Shen, Jianing Hou, Jianwei Xuan, Bao Liu
INTRODUCTION: To assess and compare per-day anti-diabetic medication costs for Chinese type-2 diabetes mellitus (T2DM) insulin-naïve patients between those who initiated premixed insulin analogs ("premixed group") and those who initiated long-acting insulin analogs ("long-acting group"). METHODS: Data were obtained from an electronic medical record database between 2010.01.01 and 2015.06.30 covering medical encounter records from all general hospitals in a district from Shanghai, China...
February 23, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Yuqian Liu, Hsuan-Yao Wang, Li Zhou, Yang Su, Wei-Chiang Shen
A recombinant proinsulin-transferrin fusion protein (ProINS-Tf) has been previously reported to be a novel long-lasting INS analog, acting specifically on the inhibition of hepatic glucose output. In this study, we investigated the biodistribution, activation and tissue retention of ProINS-Tf to elucidate its liver targeted anti-diabetic mechanism. The biodistribution study revealed that ProINS-Tf exhibited liver specific accumulation after a single intravenous injection, whereas transferrin (Tf) or insulin (INS) showed relatively even distribution among different organs...
February 20, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Alexander Zaykov, Vasily Gelfanov, Fa Liu, Richard Dennis DiMarchi, Richard Dennis DiMarchi
We report the synthesis and in vitro bioactivity assessment for an insulin-like peptide 5 (INSL5) analog that was recently discovered as a genetic mutation in an Amish population. The mutation was associated with improved metabolic status and receptor-based antagonism was proposed as a potential mechanism for the altered phenotype. We determined the specific peptide analog to be fully potent and of maximal efficacy at the human relaxin family peptide receptor 4 (RXFP-4), suggesting an alternative basis for the observed effect...
February 21, 2018: ChemMedChem
Melena D Bellin, Maisam Abu-El-Haija, Katherine Morgan, David Adams, Gregory J Beilman, Srinath Chinnakotla, Darwin L Conwell, Ty B Dunn, Martin L Freeman, Timothy Gardner, Varvara A Kirchner, Luis F Lara, Leslie Long-Simpson, Jaimie D Nathan, Bashoo Naziruddin, John A Nyman, Timothy L Pruett, Sarah J Schwarzenberg, Vikesh K Singh, Kerrington Smith, Jennifer L Steel, Martin Wijkstrom, Piotr Witkowski, James S Hodges
BACKGROUND/OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is considered for managing chronic pancreatitis in selected patients when medical and endoscopic interventions have not provided adequate relief from debilitating pain. Although more centers are performing TPIAT, we lack large, multi-center studies to guide decisions about selecting candidates for and timing of TPIAT. METHODS: Multiple centers across the United States (9 to date) performing TPIAT are prospectively enrolling patients undergoing TPIAT for chronic pancreatitis into the Prospective Observational Study of TPIAT (POST), a NIDDK funded study with a goal of accruing 450 TPIAT recipients...
February 6, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Roberto Visentin, Enrique Campos-Náñez, Michele Schiavon, Dayu Lv, Martina Vettoretti, Marc Breton, Boris P Kovatchev, Chiara Dalla Man, Claudio Cobelli
BACKGROUND: A new version of the UVA/Padova Type 1 Diabetes (T1D) Simulator is presented which provides a more realistic testing scenario. The upgrades to the previous simulator, which was accepted by the Food and Drug Administration in 2013, are described. METHOD: Intraday variability of insulin sensitivity (S I ) has been modeled, based on clinical T1D data, accounting for both intra- and intersubject variability of daily S I . Thus, time-varying distributions of both subject's basal insulin infusion and insulin-to-carbohydrate ratio were calculated and made available to the user...
February 1, 2018: Journal of Diabetes Science and Technology
Andre F Batista, Leticia Forny-Germano, Julia R Clarke, Natalia M Lyra E Silva, Jordano Brito-Moreira, Susan E Boehnke, Andrew Winterborn, Brian C Coe, Ann Lablans, Juliana F Vital, Suelen A Marques, Ana M B Martinez, Matthias Gralle, Christian Holscher, William L Klein, Jean-Christophe Houzel, Sergio T Ferreira, Douglas P Munoz, Fernanda G De Felice
Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling...
February 12, 2018: Journal of Pathology
Adarsh R Kallar, Jayabalan Muthu, Shivaram Selvam
We report the preparation of protein encapsulated amino acid derived redox-responsive nanoparticles (NPs) as effective nanocarriers for intracellular delivery of proteins. More specifically, acryloyl derivatives of lysine, ornithine, cystine and cystamine, were employed as monomers and disulfide crosslinkers for non-covalent encapsulation of model protein bovine serum albumin (BSA) and were interfacially crosslinked via free radical polymerization to form redox-responsive protein NPs. Notably, prepared NPs exhibited high protein loading content between 37 and 45%, averaged ∼400 nm in hydrodynamic size and possessed a mean surface charge of -15 mV...
February 5, 2018: Colloids and Surfaces. B, Biointerfaces
Orsolya M Palacios, Indika Edirisinghe, Meredith L Wilcox, Britt Burton-Freeman, Di Xiao, Kevin C Maki
OBJECTIVE: Replacing dietary refined carbohydrates (CHO) with protein may impact appetite and glucose and lipid metabolism in metabolically at-risk individuals. The objectives of this study were to assess the effects of consumption of a lean pork-containing, high-protein (pPro) breakfast versus a refined-CHO-rich breakfast for 2 weeks on appetite and cardiometabolic parameters in overweight or obese adults with prediabetes. METHODS: In this crossover study, overweight or obese men and women with prediabetes were provided with either a pPro breakfast meal or a refined-CHO breakfast meal to consume each day (2-week intervention, ≥ 2-week washout)...
February 9, 2018: Journal of the American College of Nutrition
Mohamed Abid, Mohamed Hsairi, Mouna Elleuch, Emna Ben Aissa
Aim: To estimate the proportion of diabetic patients on insulin, who interrupt fasting during Ramadan, and describe the reported reasons of this interruption. Design: This is a national observational survey of diabetic patients treated with insulin and fasting during the month of Ramadan 2013, proposed to all endocrinologists willing to participate. Consecutive patients were included until the required sample size, estimated at 498 patients, was obtained. Conducted among patients recruited by endocrinologists during the month following Ramadan 2013...
2018: International Journal of General Medicine
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