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Diabetes

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https://www.readbyqxmd.com/read/29233935/ligand-dependent-interaction-of-ppar%C3%AE-with-t-cell-protein-tyrosine-phosphatase-45-enhances-insulin-signaling
#1
Taesik Yoo, Sun Ah Ham, Won Jin Lee, Seon In Hwang, Jin-A Park, Jung Seok Hwang, Jinwoo Hur, Ho-Chul Shin, Sung Gu Han, Chi-Ho Lee, Dong Wook Han, Kyung Shin Paek, Han Geuk Seo
Peroxisome proliferator-activated receptor (PPAR) δ plays a pivotal role in metabolic homeostasis through its effect on insulin signaling. Although diverse genomic actions of PPARδ are postulated, the specific molecular mechanisms whereby PPARδ controls insulin signaling have not been fully elucidated. We demonstrate here that short-term activation of PPARδ results in formation of a stable complex with nuclear T cell protein tyrosine phosphatase 45 (TCPTP45) isoform. This interaction of PPARδ with TCPTP45 blocked translocation of TCPTP45 into the cytoplasm, thereby preventing its interaction with the insulin receptor, which inhibits insulin signaling...
December 12, 2017: Diabetes
https://www.readbyqxmd.com/read/29229616/glutamine-elicited-secretion-of-glucagon-like-peptide-1-glp-1-is-governed-by-an-activated-glutamate-dehydrogenase
#2
Lotta E Andersson, Liliya Shcherbina, Mahmoud Al-Majdoub, Neelanjan Vishnu, Claudia Balderas Arroyo, Jonathan Aste Carrara, Claes B Wollheim, Malin Fex, Hindrik Mulder, Nils Wierup, Peter Spégel
Glucagon-like peptide-1 (GLP-1), secreted from intestinal L-cells, glucose-dependently stimulates insulin secretion from beta-cells. This glucose-dependence prevents hypoglycemia, rendering GLP-1 analogues a useful and safe treatment modality in type-2 diabetes. While the amino acid glutamine is a potent elicitor of GLP-1 secretion, the responsible mechanism remains unclear.We investigated how GLP-1 secretion is metabolically coupled in L-cells (GLUTag) and in vivo in mice, using the insulin-secreting cell-line INS-1 832/13 as reference...
December 11, 2017: Diabetes
https://www.readbyqxmd.com/read/29229615/defective-amplifying-pathway-of-%C3%AE-cell-secretory-response-to-glucose-in-type-2-diabetes-integrated-modeling-of-in-vitro-and-in-vivo-evidence
#3
Eleonora Grespan, Toni Giorgino, Silva Arslanian, Andrea Natali, Ele Ferrannini, Andrea Mari
In vivo studies have investigated the role of β-cell dysfunction in type 2 diabetes (T2D), while in vitro research on islets has elucidated key mechanisms controlling insulin secretion rate (ISR). However, the relevance of the cellular mechanisms identified in vitro, i.e., the triggering and amplifying pathways, has not been established in vivo Furthermore, the mechanisms underpinning β-cell dysfunction in T2D remain undetermined. We propose a unifying explanation of several characteristic features of insulin secretion, both in vitro and in vivo, using a mathematical model...
December 11, 2017: Diabetes
https://www.readbyqxmd.com/read/29222368/novel-lncrna-erbb4-ir-promotes-diabetic-kidney-injury-in-db-db-mice-by-targeting-mir-29b
#4
Si F Sun, Patrick Mk Tang, Min Feng, Xiao Jun, Xiao R Huang, Ping Li, Ronal Cw Ma, Hui Y Lan
TGF-β/Smad signaling plays an important role in diabetic nephropathy. The present study identified a novel Smad3-dependent long non-coding RNA (lncRNA) Erbb4-IR in the development of type-2 diabetic nephropathy (T2DN) in db/db mice. We found that Erbb4-IR was highly expressed in T2DN of db/db mice and was specifically induced by AGE via a Smad3-dependent mechanism. The functional role of Erbb4-IR in T2DN was revealed by kidney-specific silencing of Erbb4-IR to protect against the development of T2DN such as elevated microalbuminuria, serum creatinine and progressive renal fibrosis in db/db mice, and to block AGE-induced collagen I and IV expression in mouse mesangial cells (mMCs) and mouse tubular epithelial cells (mTECs)...
December 8, 2017: Diabetes
https://www.readbyqxmd.com/read/29217655/regulation-of-lipolytic-response-and-energy-balance-by-melanocortin-2-receptor-accessory-protein-mrap-in-adipocytes
#5
Xiaodong Zhang, Alicia M Saarinen, Latoya E Campbell, Elena A De Filippis, Jun Liu
MRAP is highly expressed in adrenal gland and adipose tissue. In adrenal cells, MRAP is essential for ACTH-induced activation of the cAMP/PKA pathway by melanocortin 2 receptor (MC2R), leading to glucocorticoid production and secretion. Although ACTH was known to stimulate PKA-dependent lipolysis, the functional involvement of MRAP in adipocyte metabolism remains incompletely defined. Herein, we found that knockdown or overexpression of MRAP in 3T3-L1 adipocytes reduced or increased ACTH-induced lipolysis, respectively...
December 7, 2017: Diabetes
https://www.readbyqxmd.com/read/29217654/the-p300-and-cbp-transcriptional-coactivators-are-required-for-beta-cell-and-alpha-cell-proliferation
#6
Chi Kin Wong, Adam K Wade-Vallance, Dan S Luciani, Paul K Brindle, Francis C Lynn, William T Gibson
p300 (EP300) and CBP (CREBBP) are transcriptional coactivators with histone acetyltransferase activity. Various beta cell transcription factors can recruit p300/CBP, and thus the coactivators could be important for beta cell function and health in vivo We hypothesized that p300/CBP contribute to the development and proper function of pancreatic islets. To test this, we bred and studied mice lacking p300/CBP in their islets. Mice lacking either p300 or CBP in islets developed glucose intolerance attributable to impaired insulin secretion, together with reduced alpha and beta cell area and islet insulin content...
December 7, 2017: Diabetes
https://www.readbyqxmd.com/read/29212780/excitatory-gabaergic-action-and-increased-vasopressin-synthesis-in-hypothalamic-magnocellular-neurosecretory-cells-underlie-the-high-plasma-level-of-vasopressin-in-diabetic-rat
#7
Young-Beom Kim, Woong Bin Kim, Won Woo Jung, Xiangyan Jin, Yoon Sik Kim, Byoungjae Kim, Hee Chul Han, Gene D Block, Christopher S Colwell, Yang In Kim
Diabetes mellitus (DM) is associated with increased plasma levels of arginine-vasopressin (AVP) which may aggravate hyperglycemia and nephropathy. However, the mechanisms by which DM may cause the increased AVP levels are not known. Electrophysiological recordings in the supraoptic nucleus (SON) slices from streptozotocin-induced DM model (STZ) rats and vehicle-treated control rats revealed that GABA functions generally as an excitatory neurotransmitter in the AVP neurons of STZ rats, whereas it evoked usually inhibitory responses in the cells of control animals...
December 6, 2017: Diabetes
https://www.readbyqxmd.com/read/29212779/longitudinal-analysis-of-genetic-susceptibility-and-body-mass-index-throughout-adult-life
#8
Mingyang Song, Yan Zheng, Lu Qi, Frank B Hu, Andrew T Chan, Edward L Giovannucci
Little is known about the genetic influence on body mass index (BMI) trajectory throughout adulthood. We created a genetic risk score (GRS) comprising 97 adult BMI-associated variants among 9,971 women and 6,405 men of European ancestry. Serial measures of BMI were assessed from ages 18 (women) or 21 (men) to 85 years. We also examined BMI change in early (from age 18 or 21 to 45), middle (from age 45 to 65), and late adulthood (from age 65 to 80). GRS was positively associated with BMI across all ages, with stronger associations in women than in men...
December 6, 2017: Diabetes
https://www.readbyqxmd.com/read/29208634/the-synthetic-microneurotrophin-bnn27-affects-retinal-function-in-streptozotocin-induced-diabetic-rats
#9
Ruth Ibán-Arias, Silvia Lisa, Niki Mastrodimou, Despina Kokona, Emmanuil Koulakis, Panagiota Iordanidou, Antonis Kouvarakis, Myrto Fothiadaki, Sofia Papadogkonaki, Aggeliki Sotiriou, Haralambos E Katerinopoulos, Achille Gravanis, Ioannis Charalampopoulos, Kyriaki Thermos
BNN27, a C17-spiroepoxy derivative of DHEA, was shown to have anti-apoptotic properties via mechanisms involving the NGF receptors (TrkA/ p75NTR). In this study we examined the effects of BNN27 on neural/glial cell function, apoptosis and inflammation in the experimental rat streptozotocin (STZ)-model of diabetic retinopathy (DR). The ability of BNN27 to activate the TrkA receptor and regulate p75NTR expression was investigated. BNN27 (2,10,50mg/kg,7days,i.p.) administration four weeks post STZ-injection (Paradigm A) reversed the diabetes-induced glial activation, loss of function of amacrine cells (bNOS/TH expression) and ganglion cell axons via a TrkAR-dependent mechanism...
December 5, 2017: Diabetes
https://www.readbyqxmd.com/read/29208633/in-vivo-visualization-of-beta-cells-by-targeting-of-gpr44
#10
Olof Eriksson, Peter Johnström, Zsolt Cselenyi, Mahabuba Jahan, Ram K Selvaraju, Marianne Jensen-Waern, Akihiro Takano, Maria Sörhede Winzell, Christer Halldin, Stanko Skrtic, Olle Korsgren
GPR44 expression has recently been described as highly beta cell selective in the human pancreas and constitutes a tentative surrogate imaging biomarker in diabetes.A radiolabeled small molecule GPR44 antagonist, [11C]AZ12204657, was evaluated for visualization of beta cells in pigs and non-human primates by Positron Emission Tomography (PET) as well as in immunodeficient mice transplanted with human islets under the kidney capsule. In vitro autoradiography of human and animal pancreatic sections from non-diabetic and diabetic subjects, in combination with insulin staining, was performed to assess beta cell selectivity of the radiotracer...
December 5, 2017: Diabetes
https://www.readbyqxmd.com/read/29203512/glucocorticoids-reprogram-beta-cell-signaling-to-preserve-insulin-secretion
#11
Nicholas H F Fine, Craig L Doig, Yasir S Elhassan, Nicholas C Vierra, Piero Marchetti, Marco Bugliani, Rita Nano, Lorenzo Piemonti, Guy A Rutter, David A Jacobson, Gareth G Lavery, David J Hodson
Excessive glucocorticoid exposure has been shown to be deleterious for pancreatic beta cell function and insulin release. However, glucocorticoids at physiological levels are essential for many homeostatic processes, including glycemic control. Here, we show that corticosterone and cortisol and their less active precursors, 11-dehydrocorticosterone (11-DHC) and cortisone, suppress voltage-dependent Ca2+ channel function and Ca2+ fluxes in rodent as well as human beta cells. However, insulin secretion, maximal ATP/ADP responses to glucose and beta cell identity were all unaffected...
December 4, 2017: Diabetes
https://www.readbyqxmd.com/read/29203511/adipocyte-jak2-regulates-hepatic-insulin-sensitivity-independently-of-body-composition-liver-lipid-content-and-hepatic-insulin-signaling
#12
Kevin C Corbit, João Paulo G Camporez, Lia R Edmunds, Jennifer L Tran, Nicholas B Vera, Derek M Erion, Rahul C Deo, Rachel J Perry, Gerald I Shulman, Michael J Jurczak, Ethan J Weiss
Disruption of hepatocyte growth hormone (GH) signaling via disruption of Jak2 (JAK2L) leads to fatty liver. Previously, we demonstrated that development of fatty liver is dependent on adipocyte GH signaling. Here, we sought to determine the individual roles of hepatocyte and adipocyte Jak2 on whole body and tissue insulin sensitivity and liver metabolism. On chow, JAK2L mice had heaptic steatosis and severe whole body and hepatic insulin resistance. However, concomitant deletion of Jak2 in hepatocytes and adipocytes (JAK2LA) completely normalized insulin sensitivity while reducing liver lipid content...
December 4, 2017: Diabetes
https://www.readbyqxmd.com/read/29203510/mechanisms-to-elevate-endogenous-glucagon-like-peptide-1-glp-1-beyond-injectable-glp-1-analogues-and-metabolic-surgery
#13
Daniel A Briere, Ana B Bueno, Ellen J Gunn, M Dodson Michael, Kyle W Sloop
Therapeutic engineering of glucagon-like peptide-1 (GLP-1) has enabled development of new medicines to treat type 2 diabetes mellitus. These injectable analogues achieve robust glycemic control by increasing concentrations of 'GLP-1 equivalents' (∼50 pM). Similar levels of endogenous GLP-1 occur following gastric bypass surgery, and mechanistic studies indicate glucose lowering by these procedures is driven by GLP-1. Therefore, due to the remarkable signaling and secretory capacity of the GLP-1 system, we sought to discover mechanisms that raise GLP-1 pharmacologically...
December 4, 2017: Diabetes
https://www.readbyqxmd.com/read/29180353/clec16a-nrdp1-and-usp8-form-a-ubiquitin-dependent-tripartite-complex-that-regulates-beta-cell-mitophagy
#14
Gemma Pearson, Biaoxin Chai, Tracy Vozheiko, Xueying Liu, Malathi Kandarpa, Robert C Piper, Scott A Soleimanpour
Mitophagy is a cellular quality control pathway, which is essential to eliminate unhealthy mitochondria. While mitophagy is critical to pancreatic β-cell function, the post-translational signals governing β-cell mitochondrial turnover are unknown. Here we report that ubiquitination is essential for the assembly of a mitophagy regulatory complex, comprised of the E3 ligase Nrdp1, the deubiquitinase enzyme USP8, and Clec16a, a mediator of β-cell mitophagy with unclear function. We discover that the diabetes gene Clec16a encodes an E3 ligase, which promotes non-degradative ubiquitin conjugates to direct its mitophagy effectors and stabilize the Clec16a-Nrdp1-USP8 complex...
November 27, 2017: Diabetes
https://www.readbyqxmd.com/read/29167189/photobiodulation-inhibits-long-term-structural-and-functional-lesions-of-diabetic-retinopathy
#15
Yan Cheng, Yunpeng Du, Haitao Liu, Jie Tang, Alex Veenstra, Timothy S Kern
Previous studies demonstrated that brief (3-4 minutes), daily application of light at 670nm to diabetic rodents inhibited molecular and pathophysiologic processes implicated in the pathogenesis of diabetic retinopathy (DR), and reversed diabetic macular edema in small numbers of patients studied. Whether or not this therapy would inhibit the neural and vascular lesions that characterize the early stages of the retinopathy was unknown. We administered photobiomodulation (PBM) therapy daily for 8 months to streptozotocin-diabetic mice, and assessed effects of PBM on visual function, retinal capillary permeability, and capillary degeneration using published methods...
November 22, 2017: Diabetes
https://www.readbyqxmd.com/read/29146629/erratum-adipocyte-glucocorticoid-receptor-deficiency-attenuates-aging-and-hfd-induced-obesity-and-impairs-the-feeding-fasting-transition-diabetes-2017-66-272-286
#16
Kristina M Mueller, Kerstin Hartmann, Doris Kaltenecker, Sabine Vettorazzi, Mandy Bauer, Lea Mauser, Sabine Amann, Sigrid Jall, Katrin Fischer, Harald Esterbauer, Timo D Müller, Matthias H Tschöp, Christoph Magnes, Johannes Haybaeck, Thomas Scherer, Natalie Bordag, Jan P Tuckermann, Richard Moriggl
No abstract text is available yet for this article.
November 16, 2017: Diabetes
https://www.readbyqxmd.com/read/29141982/a-partial-loss-of-function-variant-in-akt2-is-associated-with-reduced-insulin-mediated-glucose-uptake-in-multiple-insulin-sensitive-tissues-a-genotype-based-callback-positron-emission-tomography-study
#17
Aino Latva-Rasku, Miikka-Juhani Honka, Alena Stančáková, Heikki A Koistinen, Johanna Kuusisto, Li Guan, Alisa K Manning, Heather Stringham, Anna L Gloyn, Cecilia M Lindgren, Francis S Collins, Karen L Mohlke, Laura J Scott, Tomi Karjalainen, Lauri Nummenmaa, Michael Boehnke, Pirjo Nuutila, Markku Laakso
Rare fully penetrant mutations in AKT2 are an established cause of monogenic disorders of glucose metabolism. Recently, a novel partial loss-of-function AKT2 coding variant (p.Pro50Thr) was identified that is nearly specific to Finns (frequency 1.1%), with the low-frequency allele associated with an increase in fasting plasma insulin level and risk of type 2 diabetes. The effects of p.Pro50Thr on insulin-stimulated glucose uptake (GU) in the whole body and in different tissues have not previously been investigated...
November 15, 2017: Diabetes
https://www.readbyqxmd.com/read/29138256/low-neonatal-plasma-n-6-n-3-pufa-ratios-regulate-offspring-adipogenic-potential-and-condition-adult-obesity-resistance
#18
Michael C Rudolph, Matthew R Jackman, David M Presby, Julie A Houck, Patricia G Webb, Ginger C Johnson, Taylor K Soderborg, Becky A de la Houssaye, Ivana V Yang, Jacob E Friedman, Paul S MacLean
Adipose tissue expansion (ATE) progresses rapidly during postnatal life, influenced by both prenatal maternal factors and postnatal developmental cues. The ratio of n-6 relative to n-3 polyunsaturated fatty acids (PUFA) is thought to regulate perinatal adipogenesis, but the cellular mechanisms and long-term effects are not well understood. We lowered the fetal and postnatal n-6/n-3 PUFA ratio exposure in wildtype offspring, under standard maternal dietary fat amounts, to test effects of low n-6/n-3 ratios on offspring adipogenesis and adipogenic potential...
November 14, 2017: Diabetes
https://www.readbyqxmd.com/read/29133512/exosomes-from-adipose-derived-stem-cells-attenuate-adipose-inflammation-and-obesity-through-polarizing-m2-macrophages-and-beiging-in-white-adipose-tissues
#19
Hui Zhao, Qianwen Shang, Zhenzhen Pan, Yang Bai, Zequn Li, Huiying Zhang, Qiu Zhang, Chun Guo, Lining Zhang, Qun Wang
Adipose-derived stem cells (ADSCs) play critical roles in controlling obesity-associated inflammation and metabolic disorders. Exosomes from ADSCs exert protective effects in several diseases, but their roles in obesity and related pathological conditions remain unclear. Here we showed that treatment of obese mice with ADSC-derived exosomes facilitated their metabolic homeostasis including improved insulin sensitivity (27.8% improvement), reduced obesity and alleviated hepatic steatosis. ADSC-derived exosomes drove M2 macrophage polarization, inflammation reduction and beiging in white adipose tissues (WAT) of diet-induced obese mice...
November 13, 2017: Diabetes
https://www.readbyqxmd.com/read/29109245/expression-of-concern-protein-kinase-c-pkc-%C3%AE-activation-inhibits-pkc-%C3%AE-and-mediates-the-action-of-ped-pea-15-on-glucose-transport-in-the-l6-skeletal-muscle-cells-diabetes-2001-50-1244-1252-doi-https-doi-org-10-2337-diabetes-50-6-1244-pmid-11375323
#20
Gerolama Condorelli, Giovanni Vigliotta, Alessandra Trencia, Maria Alessandra Maitan, Matilde Caruso, Claudia Miele, Francesco Oriente, Stefania Santopietro, Pietro Formisano, Francesco Beguinot
No abstract text is available yet for this article.
November 6, 2017: Diabetes
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