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Insulin secretion

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https://www.readbyqxmd.com/read/27933575/-fast-acting-insulin-new-developments-towards-more-flexibility-for-the-patient
#1
Gerhard W Schmeisl, Yasmin Kretzschmar
BACKGROUND: Post-prandial insulin secretion occurs under physiological conditions very fast and in adequate concentrations. This mechanism is impaired in patients with type 2 diabetes and severe increases of postprandial glucose levels may occur. In order to achieve physiological conditions and to avoid postprandial hyperglycemia, exogenous insulin and insulin analogues should be absorbed very fast and appropriate maximum concentrations should be reached very quickly. METHOD: Overview RESULTS AND CONCLUSIONS: The development of new bolus insulins is focused on improved pharmacokinetic and pharmacodynamic properties...
December 2016: MMW Fortschritte der Medizin
https://www.readbyqxmd.com/read/27933333/discriminatory-ability-of-simple-ogtt-based-beta-cell-function-indices-for-prediction-of-prediabetes-and-type-2-diabetes-the-codam-study
#2
Louise J C J den Biggelaar, Simone J S Sep, Simone J P M Eussen, Andrea Mari, Ele Ferrannini, Marleen M J van Greevenbroek, Carla J H van der Kallen, Casper G Schalkwijk, Coen D A Stehouwer, Pieter C Dagnelie
AIMS/HYPOTHESIS: The hyperglycaemic clamp technique and the frequently sampled IVGTT are unsuitable techniques to assess beta cell function (BCF) in large cohorts. Therefore, the aim of this study was to evaluate the discriminatory ability of simple OGTT-based BCF indices for prediction of prediabetes (meaning impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes. METHODS: Glucose metabolism status was assessed by 2 h 75 g OGTT at baseline (n = 476, mean age 59...
December 8, 2016: Diabetologia
https://www.readbyqxmd.com/read/27933272/autophagy-dependent-secretion-contribution-to-tumor-progression
#3
REVIEW
Tom G Keulers, Marco B E Schaaf, Kasper M A Rouschop
Autophagy is best known as a lysosomal degradation and recycling pathway to maintain cellular homeostasis. During autophagy, cytoplasmic content is recognized and packed in autophagic vacuoles, or autophagosomes, and targeted for degradation. However, during the last years, it has become evident that the role of autophagy is not restricted to degradation alone but also mediates unconventional forms of secretion. Furthermore, cells with defects in autophagy apparently are able to reroute their cargo, like mitochondria, to the extracellular environment; effects that contribute to an array of pathologies...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27932304/vitamin-d-and-type-2-diabetes
#4
REVIEW
Paul Lips, Marelise Eekhoff, Natasja Vzn Schoor, Mirjam Oosterwerff, Renate de Jongh, Yvonne Krul-Poel, Suat Simsek
Vitamin D deficiency is associated with a decreased insulin release, insulin resistance and type 2 diabetes in experimental and epidemiological studies. Animal studies show that 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) stimulates the pancreatic β-cell to secrete insulin. The relationship between vitamin D deficiency and insulin resistance could develop through inflammation, as vitamin D deficiency is associated with increased inflammatory markers. In addition, genetic polymorphisms of vitamin D -related genes may predispose to impaired glycemic control and type 2 diabetes...
December 5, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27932063/toward-connecting-metabolism-to-the-exocytotic-site
#5
REVIEW
Mourad Ferdaoussi, Patrick E MacDonald
Within cells the regulated exocytosis of secretory granules controls multiple physiological functions, including endocrine hormone secretion. Release of the glucose-regulating hormone insulin from pancreatic islet β cells is critical for whole-body metabolic homeostasis. Impaired insulin secretion appears early in the progression to type 2 diabetes (T2D). Key mechanisms that control the β-cell exocytotic response, mediating the long-known but little understood metabolic amplification of insulin secretion, are becoming clearer...
December 5, 2016: Trends in Cell Biology
https://www.readbyqxmd.com/read/27928899/alleviating-vldl-overproduction-is-an-important-mechanism-for-laminaria-japonica-polysaccharide-to-inhibit-atherosclerosis-in-ldlr-mice-with-diet-induced-insulin-resistance
#6
Xue-Qiang Zha, Wei-Nan Zhang, Fu-Hua Peng, Lei Xue, Jian Liu, Jian-Ping Luo
SCOPE: The overproduction of very low density lipoprotein (VLDL) is an important cause for initiation and development of atherosclerosis, which is highly associated with insulin signaling. The aim of this work is to verify whether the inhibition of VLDL overproduction is an underlying mechanism for a Laminaria japonica polysaccharide (LJP61A) to resist atherosclerosis. METHODS AND RESULTS: LJP61A (50 and 200 mg/Kg/day) was orally administered to a high fat diet (HFD)-fed LDLr(-/-) mice for 14 weeks...
December 8, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27928437/increased-copeptin-levels-in-metabolic-syndrome-from-a-romanian-population
#7
Vintilă M, Gheorghiu Ml, Caragheorgheopol A, Baculescu N, Lichiardopol C, Badiu C, Coculescu M, Grigorescu F, Poiană C
Rationale: Arginine vasopressin (AVP) is secreted under conditions of water deprivation. Since AVP has a low half-life in the plasma, the C-terminal fragment of AVP-precursor (copeptin) was used to estimate the AVP levels. High copeptin levels increase the risk for the development of diabetes mellitus. Aim: This study was aimed to measure copeptin levels in the metabolic syndrome (MetS) in Romanians using a competitive enzyme immunoassay. Methods and results: Patients prone to present MetS (n = 63) were compared to controls (n = 42)...
October 2016: Journal of Medicine and Life
https://www.readbyqxmd.com/read/27928162/role-of-mirnas-in-the-pathogenesis-and-susceptibility-of-diabetes-mellitus
#8
REVIEW
Naoko Hashimoto, Tomoaki Tanaka
MicroRNAs (miRNAs) are noncoding RNAs of ~22 nucleotides that regulate gene expression post-transcriptionally by binding to the 3' untranslated region of messenger RNA (mRNAs), resulting in inhibition of translation or mRNA degradation. miRNAs have a key role in fine-tuning cellular functions such as proliferation, differentiation and apoptosis, and they are involved in carcinogenesis, glucose homeostasis, inflammation and other biological processes. In this review, we focus on the role of miRNAs in the pathophysiology of the metabolic disease and diabetes mellitus, the hallmark of which is hyperglycemia caused by defective insulin secretion and/or action...
December 8, 2016: Journal of Human Genetics
https://www.readbyqxmd.com/read/27927801/physiological-aging-links-among-adipose-tissue-dysfunction-diabetes-and-frailty
#9
REVIEW
Michael B Stout, Jamie N Justice, Barbara J Nicklas, James L Kirkland
Advancing age is associated with progressive declines in physiological function that lead to overt chronic disease, frailty, and eventual mortality. Importantly, age-related physiological changes occur in cellularity, insulin-responsiveness, secretory profiles, and inflammatory status of adipose tissue, leading to adipose tissue dysfunction. Although the mechanisms underlying adipose tissue dysfunction are multifactorial, the consequences result in secretion of proinflammatory cytokines and chemokines, immune cell infiltration, an accumulation of senescent cells, and an increase in senescence-associated secretory phenotype (SASP)...
January 2017: Physiology
https://www.readbyqxmd.com/read/27927751/rab2a-and-rab27a-cooperatively-regulate-transition-from-granule-maturation-to-exocytosis-through-the-dual-effector-noc2
#10
Kohichi Matsunaga, Masato Taoka, Toshiaki Isobe, Tetsuro Izumi
Exocytosis of secretory granules entails budding from the trans-Golgi network, sorting and maturation of cargo proteins, and trafficking and fusion to the plasma membrane. Rab27a regulates the late steps in this process, such as granule recruitment to the fusion site, whereas Rab2a functions in the early steps, such as granule biogenesis and maturation. Here, we demonstrate that these two small GTPases simultaneously bind to Noc2 in GTP-dependent manners, although Rab2a binds only after Rab27a has bound. In pancreatic beta cells, the ternary Rab2a-Noc2-Rab27a complex specifically localizes on perinuclear immature granules, whereas the binary Noc2-Rab27a complex localizes on peripheral mature granules...
December 7, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27927723/coordinated-activation-of-mitochondrial-respiration-and-exocytosis-mediated-by-pkc-signaling-in-pancreatic-%C3%AE-cells
#11
Jaime Santo-Domingo, Isabelle Chareyron, Loïc Dayon, Antonio Núñez Galindo, Ornella Cominetti, María Pilar Giner Giménez, Umberto De Marchi, Carles Canto, Martin Kussmann, Andreas Wiederkehr
Mitochondria play a central role in pancreatic β-cell nutrient sensing by coupling their metabolism to plasma membrane excitability and insulin granule exocytosis. Whether non-nutrient secretagogues stimulate mitochondria as part of the molecular mechanism to promote insulin secretion is not known. Here, we show that PKC signaling, which is employed by many non-nutrient secretagogues, augments mitochondrial respiration in INS-1E (rat insulinoma cell line clone 1E) and human pancreatic β-cells. The phorbol ester, phorbol 12-myristate 13-acetate, accelerates mitochondrial respiration at both resting and stimulatory glucose concentrations...
December 7, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27927722/age-dependent-control-of-energy-homeostasis-by-brown-adipose-tissue-in-progeny-subjected-to-maternal-diet-induced-fetal-programming
#12
Olivier Dumortier, Estelle Roger, Didier F Pisani, Virginie Casamento, Nadine Gautier, Patricia Lebrun, Hereroa Johnston, Pascal Lopez, Ez-Zoubir Amri, Céline Jousse, Pierre Fafournoux, Marc Prentki, Charlotte Hinault, Emmanuel Van Obberghen
Epidemiological and animal studies show that deleterious maternal environments predispose aging offspring to metabolic disorders and type 2 diabetes. Young progeny in a rat model of maternal low protein diet (LP) is normoglycemic despite collapsed insulin secretion. However, without further worsening of the insulin secretion defect glucose homeostasis deteriorates in aging LP descendants. Here we report that normoglycemic and insulinopenic 3-month-old LP progeny shows increased body temperature and energy dissipation in association with enhanced brown adipose tissue (BAT) activity...
December 7, 2016: Diabetes
https://www.readbyqxmd.com/read/27926891/type-2-diabetes-the-pathologic-basis-of-reversible-%C3%AE-cell-dysfunction
#13
REVIEW
Michael G White, James A M Shaw, Roy Taylor
The reversible nature of early type 2 diabetes has been demonstrated in in vivo human studies. Recent in vivo and in vitro studies of β-cell biology have established that the β-cell loses differentiated characteristics, including glucose-mediated insulin secretion, under metabolic stress. Critically, the β-cell dedifferentiation produced by long-term excess nutrient supply is reversible. Weight loss in humans permits restoration of first-phase insulin secretion associated with the return to normal of the elevated intrapancreatic triglyceride content...
November 2016: Diabetes Care
https://www.readbyqxmd.com/read/27926473/growth-differentiation-factor-15-increases-following-oral-glucose-ingestion-effect-of-meal-composition-and-obesity
#14
Marie Helene Schernthaner-Reiter, Dominik Kasses, Christina Tugendsam, Michaela Riedl, Slobodan Peric, Gerhard Prager, Michael Krebs, Miriam Promintzer-Schifferl, Martin Clodi, Anton Luger, Greisa Vila
OBJECTIVE: Growth differentiation factor 15 (GDF15) is a cardiovascular biomarker belonging to the transforming growth factor-β superfamily. Increased GDF15 concentrations are associated with insulin resistance, diabetes and obesity. We investigated the physiological effects of meal composition and obesity on the regulation of systemic GDF15 levels. DESIGN: Lean (n = 8) and obese (n = 8) individuals received a carbohydrate- or fat-rich meal, a 75 g oral glucose load (OGTT) or short-term fasting...
December 2016: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27925205/generation-of-insulin-producing-cells-from-human-induced-pluripotent-stem-cells-using-a-stepwise-differentiation-protocol-optimized-with-platelet-rich-plasma
#15
Seyed Ehsan Enderami, Yousef Mortazavi, Masoud Soleimani, Samad Nadri, Alireza Biglari, Reyhaneh Nassiri Mansour
Studies on patient-specific human-induced pluripotent stem cells (hiPSCs) as well as a series of autologous growth factors presumably will reveal their many benefits for cell base replacement therapy in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a multistep protocol by adding platelet-rich plasma (PRP) that induce the hiPSCs into insulin-producing cells (IPCs). We present here a differentiation protocol consisting of five stages in two groups including protocol with PRP and without PRP...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924813/taotie-neurons-regulate-appetite-in-drosophila
#16
Yin Peng Zhan, Li Liu, Yan Zhu
The brain has an essential role in maintaining a balance between energy intake and expenditure of the body. Deciphering the processes underlying the decision-making for timely feeding of appropriate amounts may improve our understanding of physiological and psychological disorders related to feeding control. Here, we identify a group of appetite-enhancing neurons in a behavioural screen for flies with increased appetite. Manipulating the activity of these neurons, which we name Taotie neurons, induces bidirectional changes in feeding motivation...
December 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27923328/modeling-stroma-induced-drug-resistance-in-a-tissue-engineered-tumor-model-of-ewing-sarcoma
#17
Marco Santoro, Brian A Menegaz, Salah-Eddine Lamhamedi-Cherradi, Eric R Molina, Danielle Wu, Waldemar Priebe, Joseph A Ludwig, Antonios G Mikos
Three-dimensional (3D) tumor models are gaining traction in the research community given their capacity to mimic aspects of the tumor microenvironment absent in monolayer systems. In particular, the ability to spatiotemporally control cell placement within ex vivo 3D systems has enabled the study of tumor-stroma interactions. Furthermore, by regulating biomechanical stimuli, one can reveal how biophysical cues affect stromal cell phenotype and how their phenotype impacts tumor drug sensitivity. Both tumor architecture and shear force have profound effects on Ewing sarcoma (ES) cell behavior and are known to elicit ligand-mediated activation of the insulin-like growth factor-1 receptor (IGF-1R), thereby mediating resistance of ES cells to IGF-1R inhibitors...
December 6, 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27923249/thyroid-function-in-human-obesity-underlying-mechanisms
#18
L C Fontenelle, M M Feitosa, J S Severo, T E C Freitas, J B S Morais, F L Torres-Leal, G S Henriques, D do Nascimento Marreiro
Obesity is associated with several metabolic and endocrine disorders; and changes in plasma concentrations, secretion patterns, and clearance of various hormones are observed in obese patients. In this context, recent research has shown that overweight can influence the function of the thyroid gland, usually leading to increased thyrotropin concentrations and changes in the ratio between the hormones triiodothyronine and thyroxine, though within the normal range. The etiology of these changes is still unclear; however, several mechanisms have been proposed including the adaptive process to increase energy expenditure, hyperleptinemia, changes in the activity of deiodinases, the presence of thyroid hormones resistance, chronic low-grade inflammation, and insulin resistance...
December 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/27922752/abnormal-glucose-metabolism-and-high-energy-expenditure-in-idiopathic-pulmonary-arterial-hypertension
#19
Gustavo A Heresi, Steven K Malin, Jarrod W Barnes, Liping Tian, John P Kirwan, Raed A Dweik
RATIONALE: Insulin resistance has emerged as a potential mechanism related to the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH). However, direct measurements of insulin and glucose metabolism have not been performed in IPAH patients to date. OBJECTIVES: To perform comprehensive metabolic phenotyping on humans with IPAH. METHODS: We assessed plasma insulin and glucose using an oral glucose tolerance test and estimated insulin resistance and beta-cell function in 14 IPAH patients and 14 controls matched for age, sex, blood pressure, and body mass index (BMI),...
December 6, 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27922139/are-low-sun-exposure-and-or-vitamin-d-risk-factors-for-type-1-diabetes
#20
K M Miller, P H Hart, N H de Klerk, E A Davis, R M Lucas
The global variation in type 1 diabetes (T1D) incidence rates is one of the most significant observed for any non-communicable disease. Geographical patterns in incidence suggest that low sun exposure may contribute to the wide disparity, with incidence rates generally increasing with distance from the Equator. T1D development is associated with hyperactivity of the adaptive immune system leading to autoimmune destruction of insulin-secreting pancreatic β cells. Both exposure to ultraviolet radiation (UVR) and vitamin D, with their known immunosuppressive effects, have the potential to delay or inhibit the disease...
December 6, 2016: Photochemical & Photobiological Sciences
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