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Insulin secretion

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https://www.readbyqxmd.com/read/28544644/%C3%AE-cell-function-in-postmenopausal-women-with-isolated-postchallenge-hyperglycemia
#1
Chii-Min Hwu, Yi-Chun Lin, Kuan-Hung Lin
BACKGROUND: Isolated postchallenge hyperglycemia (IPH) is an early stage of type 2 diabetes mellitus (T2DM) with fasting glucose < 126 mg/dL and 2 h glucose ≥ 200 mg/dL. Observations of insulin secretion profile in subjects with IPH may provide insight to the pathogenesis of T2DM in older women. METHODS: We recruited 555 naturally postmenopausal women without a history of T2DM for this study. All participants received a 75 g oral glucose tolerance test to examine if they had IPH...
May 22, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28544548/assessment-of-factors-determining-an-hba1c-concentration%C3%A2-%C3%A2-%C3%A2-7-5-in-patients-with-type-1-diabetes
#2
Eijiro Yamada, Shuichi Okada, Yasuyo Nakajima, Claire Bastie, Yuko Tagaya, Aya Osaki, Yoko Shimoda, Ryo Shibusawa, Tsugumichi Saito, Atsushi Ozawa, Masanobu Yamada
BACKGROUND: Establishing an optimal insulin regimen is crucial for maintaining glycemic control in patients with type 1 diabetes. We aimed to determine the insulin dose required to achieve a hemoglobin A1c (HbA1c) concentration ≤ 7.5% in Japanese patients with type 1 diabetes. METHODS: This multi-centered cross-sectional study was performed at 3 institutions in Japan. Among 107 patients with type 1 diabetes, 92 had no detectable endogenous insulin secretion: 39 patients had HbA1c concentration ≤ 7...
May 22, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28544529/excess-cholesterol-inhibits-glucose-stimulated-fusion-pore-dynamics-in-insulin-exocytosis
#3
Yingke Xu, Derek K Toomre, Jonathan S Bogan, Mingming Hao
Type 2 diabetes is caused by defects in both insulin sensitivity and insulin secretion. Glucose triggers insulin secretion by causing exocytosis of insulin granules from pancreatic β-cells. High circulating cholesterol levels and a diminished capacity of serum to remove cholesterol from β-cells are observed in diabetic individuals. Both of these effects can lead to cholesterol accumulation in β-cells and contribute to β-cell dysfunction. However, the molecular mechanisms by which cholesterol accumulation impairs β-cell function remain largely unknown...
May 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28543410/the-diagnosis-of-equine-insulin-dysregulation
#4
REVIEW
F R Bertin, M A de Laat
Insulin dysregulation is the hallmark of Equine Metabolic Syndrome and has received attention because of its direct association with laminitis. In the absence of an adequate treatment for laminitis, a focus on prophylaxis is needed, making early detection of individuals at risk of developing laminitis one of the main challenges in equine endocrinology. Recent studies have shown that insulin dysregulation goes beyond tissue insulin resistance and it is now demonstrated that the equine enteroinsular axis plays a major role in insulin secretion and equine hyperinsulinaemia...
May 22, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28542631/concordance-of-bioactive-vs-total-immunoreactive-serum-leptin-levels-in-children-with-severe-early-onset-obesity
#5
Juraj Stanik, Jürgen Kratzsch, Kathrin Landgraf, Kathrin Scheuermann, Ulrike Spielau, Ruth Gausche, Daniela Gasperikova, Wieland Kiess, Antje Körner
CONTEXT: Leptin secreted from adipose tissue signals peripheral energy status to the brain. Monogenic leptin deficiency results in severe early onset obesity with hyperphagia. Recently, a similar phenotype of inactivating leptin mutations but with preserved immunoreactivity and hence normal circulating immunoreactive leptin has been reported. OBJECTIVE: We aimed to evaluate the proportion of bioactive leptin serum levels (compared to immunoreactive leptin) as a biomarker for the screening of leptin gene mutations causing monogenic obesity...
2017: PloS One
https://www.readbyqxmd.com/read/28542610/gpr40-partial-agonist-mk-2305-lower-fasting-glucose-in-the-goto-kakizaki-rat-via-suppression-of-endogenous-glucose-production
#6
Corin Miller, Michele J Pachanski, Melissa E Kirkland, Daniel T Kosinski, Joel Mane, Michelle Bunzel, Jin Cao, Sarah Souza, Brande Thomas-Fowlkes, Jerry Di Salvo, Adam B Weinglass, Xiaoyan Li, Robert W Myers, Kevin Knagge, Paul E Carrington, William K Hagmann, Maria E Trujillo
GPR40 (FFA1) is a fatty acid receptor whose activation results in potent glucose lowering and insulinotropic effects in vivo. Several reports illustrate that GPR40 agonists exert glucose lowering in diabetic humans. To assess the mechanisms by which GPR40 partial agonists improve glucose homeostasis, we evaluated the effects of MK-2305, a potent and selective partial GPR40 agonist, in diabetic Goto Kakizaki rats. MK-2305 decreased fasting glucose after acute and chronic treatment. MK-2305-mediated changes in glucose were coupled with increases in plasma insulin during hyperglycemia and glucose challenges but not during fasting, when glucose was normalized...
2017: PloS One
https://www.readbyqxmd.com/read/28542222/differential-expression-of-islet-glutaredoxin-1-and-5-with-high-reactive-oxygen-species-production-in-a-mouse-model-of-diabesity
#7
Sebastian Friedrich Petry, Fatemeh Sharifpanah, Heinrich Sauer, Thomas Linn
The onset and progression of diabetes mellitus type 2 is highly contingent on the amount of functional beta-cell mass. An underlying cause of beta-cell decay in diabetes is oxidative stress, which markedly affects the insulin producing pancreatic cells due to their poor antioxidant defence capacity. Consequently, disturbances of cellular redox signaling have been implicated to play a major role in beta-cell loss in diabetes mellitus type 2. There is evidence suggesting that the glutaredoxin (Grx) system exerts a protective role for pancreatic islets, but the exact mechanisms have not yet been elucidated...
2017: PloS One
https://www.readbyqxmd.com/read/28542139/regulator-of-g-protein-signaling-2-is-a-key-regulator-of-pancreatic-%C3%AE-cell-mass-and-function
#8
H Dong, Y Zhang, J Wang, D S Kim, H Wu, B Sjögren, W Gao, L Luttrell, H Wang
Pancreatic β-cell death and dysfunction contributes to the pathogenesis of both type 1 and type 2 diabetes. We aimed to examine whether the regulator of G protein signaling protein 2 (RGS2), a multifunctional inhibitor of G protein-coupled receptor (GPCR) signaling, impacts β-cell death and function. Metabolic phenotypes, β-cell secretory function, and glucose and insulin tolerance were measured in RGS2 knockout (RGS2(-/-)) mice and their wild-type (RGS2(+/+)) littermate controls. β-Cell death was evaluated in RGS2-knockdown and -overexpressing β cells and RGS2(-/-) islets by flow cytometry, western blot, ELISA, TUNEL staining, and apoptosis RT(2) profiler PCR array analysis...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28540689/involvement-of-micrornas-in-diabetes-and-its-complications
#9
Bin Wu, Daniel Miller
Diabetes is a severe condition worldwide. It is characterized by chronic hyperglycemia and is caused by defects in insulin production, secretion, and action. Both genetic and environmental factors contribute to the development of type 1 and type 2 diabetes. The pathogenesis of diabetes is complex and the underlying molecular mechanisms are only partially understood. MicroRNAs (miRNAs) play a fundamental role in diabetes and its complications. This chapter focuses on the dysregulation of miRNAs involved in the regulation of pancreatic islet insulin production and secretion as well as action and signaling in peripheral tissues...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28540469/a-3d-microfluidic-perfusion-system-made-from-glass-for-multiparametric-analysis-of-stimulus-secretioncoupling-in-pancreatic-islets
#10
Torben Schulze, Kai Mattern, Eike Früh, Lars Hecht, Ingo Rustenbeck, Andreas Dietzel
Microfluidic perfusion systems (MPS) are well suited to perform multiparametric measurements with small amounts of tissue to function as an Organ on Chip device (OOC). Such microphysiolgical characterization is particularly valuable in research on the stimulus-secretion-coupling of pancreatic islets. Pancreatic islets are fully functional competent mini-organs, which serve as fuel sensors and transduce metabolic activity into rates of hormone secretion. To enable the simultaneous measurement of fluorescence and oxygen consumption we designed a microfluidic perfusion system from borosilicate glass by 3D femtosecond laser ablation...
September 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28539721/phytochemical-and-biological-evaluations-of-arum-hygrophilum-boiss-araceae
#11
Fatma U Afifi, Violet Kasabri, Simona Litescu, Ismail F Abaza, Khalid Tawaha
BACKGROUND: Arum hygrophilum is a traditional medicinal plant indigenous to Jordan. The present study explores its phytochemistry, antioxidative, antidiabesity, and antiproliferative potentialities. MATERIALS AND METHODS: Column chromatography and HPLC-MS analysis were used for its phytochemical evaluation. Using leaf crude water and ethanol extracts, the antioxidative capacities, their modulation of pancreatic β-cell proliferation, and insulin secretion as well as glucose diffusion and enzymatic bioassays were evaluated...
April 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28539593/identification-of-the-matricellular-protein-fibulin-5-as-a-target-molecule-of-glucokinase-mediated-calcineurin-nfat-signaling-in-pancreatic-islets
#12
Tomoko Okuyama, Jun Shirakawa, Hiromi Yanagisawa, Mayu Kyohara, Shunsuke Yamazaki, Kazuki Tajima, Yu Togashi, Yasuo Terauchi
Glucokinase-mediated glucose signaling induces insulin secretion, proliferation, and apoptosis in pancreatic β-cells. However, the precise molecular mechanisms underlying these processes are not clearly understood. Here, we demonstrated that glucokinase activation using a glucokinase activator (GKA) significantly upregulated the expression of Fibulin-5 (Fbln5), a matricellular protein involved in matrix-cell signaling, in isolated mouse islets. The islet Fbln5 expression was induced by ambient glucose in a time- and dose-dependent manner and further enhanced by high-fat diet or the deletion of insulin receptor substrate 2 (IRS-2), whereas the GKA-induced increase in Fbln5 expression was diminished in Irs-2-deficient islets...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539232/adipose-angiotensin-ii-type-1-receptor-associated-protein-ameliorates-metabolic-disorders-via-promoting-adipose-tissue-adipogenesis-and-browning
#13
Chengting Luo, Na Lv, Zai Chang, Qiannuo Qu, Jianzhen Huang
Adipose tissue is a complicated organ that not only stores excess energy, but also secrets many adipokines regulating whole-body energy hemostasis. Dysfunction of adipose tissue leads to metabolic disorders such as insulin resistance, hypertension, cardiovascular diseases. In this study, we generated a mouse model with overexpression of Angiotensin II type 1 receptor-associated protein (ATRAP) in adipose tissue specifically. Under a normal diet, ATRAP transgene (TgATRAP) mice showed similar bodyweight, fat mass and insulin sensitivity with wild-type controls (WT)...
May 17, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28538729/cryo-em-structure-of-the-activated-glp-1-receptor-in-complex-with-a-g-protein
#14
Yan Zhang, Bingfa Sun, Dan Feng, Hongli Hu, Matthew Chu, Qianhui Qu, Jeffrey T Tarrasch, Shane Li, Tong Sun Kobilka, Brian K Kobilka, Georgios Skiniotis
Glucagon-like peptide 1 (GLP-1) is a hormone with essential roles in regulating insulin secretion, carbohydrate metabolism and appetite. GLP-1 effects are mediated through binding to the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor (GPCR) that signals primarily through the stimulatory G protein Gs. Class B GPCRs are important therapeutic targets; however, our understanding of their mechanism of action is limited by the lack of structural information on activated and full-length receptors. Here we report the cryo-electron microscopy structure of the peptide-activated GLP-1R-Gs complex at near atomic resolution...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28536423/fam3b-mediates-high-glucose-induced-vascular-smooth-muscle-cell-proliferation-and-migration-via-inhibition-of-mir-322-5p
#15
Wenxiang Zhang, Siyu Chen, Zhao Zhang, Chen Wang, Chang Liu
The proliferation and migration of vascular smooth muscle cells (VSMCs) play an essential role during the development of cardiovascular diseases (CVDs). While many factors potentially contribute to the abnormal activation of VSMCs, hyperglycemia is generally believed to be a major causative factor. On the other hand, FAM3B (named PANDER for its secretory form) is a uniquely structured protein strongly expressed within and secreted from the endocrine pancreas. FAM3B is co-secreted with insulin from the β-cell upon glucose stimulation and regulates glucose homeostasis...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536182/glucagon-s-effect-on-liver-protein-metabolism-in-vivo
#16
Guillaume Kraft, Katie C Coate, Jason J Winnick, Dominique Dardevet, E Patrick Donahue, Alan D Cherrington, Phillip E Williams, Mary Courtney Moore
The postprandial state is characterized by a storage of nutrients in the liver, muscle and adipose tissue for later utilization. In the case of a protein rich meal, amino acids (AA) stimulate glucagon secretion by the α-cell. The aim of the present study was to determine the impact of the rise in glucagon on AA metabolism, particularly in the liver. We used a conscious catheterized dog model to recreate a postprandial condition using a pancreatic clamp. Portal infusions of glucose, AA and insulin were used to achieve postprandial levels while portal glucagon infusion either maintained the basal level or increased it by 3 fold...
May 23, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28535646/-the-research-advances-in-the-relationship-between-visfatin-and-cancer
#17
W Y Tian, Y M Wang, Y F Zhang, F X Xue
Visfatin is a cytokine secreted by visceral adipose tissue, which plays an important role in obesity, diabetes, insulin resistance, atherosclerosis and polycystic ovarian syndrome. Additionally, visfatin is also involved in the metabolic syndrome-associated malignancies such as breast, colon, gastric and endometrial cancers. Visfatin inhibitor might be a potential antitumor therapeutic strategy for inhibiting the growth of many cancers.
May 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28535085/characterization-of-an-encapsulated-insulin-secreting-human-pancreatic-beta-cell-line-in-a-modular-microfluidic-device
#18
Argia Acarregui, Jesús Ciriza, Laura Saenz Del Burgo, Haritz Gurruchaga, José Yeste, Xavier Illa, Gorka Orive, Rosa M Hernández, Rosa Villa, Jose Luis Pedraz
Type I diabetes mellitus is characterized by the destruction of the insulin producing beta cells within the pancreas by the immune system. After the success of Edmonton protocol, islet transplantation has shown to be a promising therapy, but with the Achilles´ heel of the need of using immunosuppressive drugs. Currently, cell encapsulation technology represents a real alternative to protect transplanted islets from the host´s immune attack. Although preliminary in vitro studies with encapsulated cells have been traditionally performed under static conditions in terms of viability and efficiency, these static cultures do not represent a close approach to in vivo environments...
May 23, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28534682/diabetic-ketoacidosis-a-common-debut-of-diabetes-among-african-americans-with-type-2-diabetes
#19
Priyathama Vellanki, Guillermo E Umpierrez
OBJECTIVE: More than half of African Americans (AA) with a new diagnosis of diabetic ketoacidosis have clinical and metabolic features of type 2 diabetes during follow-up. This particular presentation of diabetes has been termed as ketosis-prone type 2 diabetes (KPDM) or atypical diabetes. METHODS: We review the epidemiology, diagnosis, pathophysiology and acute and long-term management of AA with KPDM and compare these similarities to patients with type 2 diabetes...
May 23, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28534511/stromal-derived-igf2-promotes-colon-cancer-progression-via-paracrine-and-autocrine-mechanisms
#20
C Unger, N Kramer, D Unterleuthner, M Scherzer, A Burian, A Rudisch, M Stadler, M Schlederer, D Lenhardt, A Riedl, S Walter, A Wernitznig, L Kenner, M Hengstschläger, J Schüler, W Sommergruber, H Dolznig
The insulin-like growth factor (IGF)2/IGF1 receptor (IGF1R) signaling axis has an important role in intestinal carcinogenesis and overexpression of IGF2 is an accepted risk factor for colorectal cancer (CRC) development. Genetic amplifications and loss of imprinting contribute to the upregulation of IGF2, but insufficiently explain the extent of IGF2 expression in a subset of patients. Here, we show that IGF2 was specifically induced in the tumor stroma of CRC and identified cancer-associated fibroblasts (CAFs) as the major source...
May 22, 2017: Oncogene
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