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pancreatitis AND insulin

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https://www.readbyqxmd.com/read/30517875/integrated-in-vivo-quantitative-proteomics-and-nutrient-tracing-reveals-age-related-metabolic-rewiring-of-pancreatic-%C3%AE-cell-function
#1
Matthew Wortham, Jacqueline R Benthuysen, Martina Wallace, Jeffrey N Savas, Francesca Mulas, Ajit S Divakaruni, Fenfen Liu, Verena Albert, Brandon L Taylor, Yinghui Sui, Enrique Saez, Anne N Murphy, John R Yates, Christian M Metallo, Maike Sander
Pancreatic β cell physiology changes substantially throughout life, yet the mechanisms that drive these changes are poorly understood. Here, we performed comprehensive in vivo quantitative proteomic profiling of pancreatic islets from juvenile and 1-year-old mice. The analysis revealed striking differences in abundance of enzymes controlling glucose metabolism. We show that these changes in protein abundance are associated with higher activities of glucose metabolic enzymes involved in coupling factor generation as well as increased activity of the coupling factor-dependent amplifying pathway of insulin secretion...
December 4, 2018: Cell Reports
https://www.readbyqxmd.com/read/30515793/protective-effects-of-either-c-peptide-or-l-arginine-on-pancreatic-%C3%AE-cell-function-proliferation-and-oxidative-stress-in-streptozotocin-induced-diabetic-rats
#2
Merhan Mamdouh Ragy, Sabreen Mahmoud Ahmed
Diabetes and cardiometabolic risk factors including hypertension and dyslipidemia are the major threats to human health in the 21st century. Apoptosis in pancreatic tissue is one of the major causes of diabetes type 1 progression. The aim of this study was to investigate the effects of C-peptide or l-arginine on some cardiometabolic risk factors, pancreatic morphology, function and apoptosis, and the mechanisms of their actions. Forty adult male albino rats were divided into four equal groups: 1-control nondiabetic, 2-diabetic (no treatment), 3-diabetic + C-peptide, and 4-diabetic +  l-arginine...
December 4, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30514191/a-review-of-type-2-diabetes-mellitus-predisposing-genes
#3
Tajudeen O Yahaya, Titilola F Salisu
INTRODUCTION: Scientists are considering the possibility of treating diabetes mellitus (DM) using a personalized approach in which various forms of the diseases will be treated based on the causal gene and its pathogenesis. To this end, scientists have identified mutations in certain genes as probable causes of Type 2 diabetes mellitus (T2DM) with diverse mechanisms. AIM: This review was aimed at articulating already identified T2DM genes with their mechanisms of action and phenotypic presentations for the awareness of all stakeholders...
December 4, 2018: Current Diabetes Reviews
https://www.readbyqxmd.com/read/30512986/involvement-of-the-stat5-cyclind-cdk4-prb-pathway-in-beta-cell-proliferation-stimulated-by-prolactin-during-pregnancy
#4
Xin Zhao, Yili Xu, Ya Wu, Hui Zhang, Houxia Shi, Hui Zhu, Minna Woo, Xiaohong Wu
During pregnancy, maternal pancreatic beta cells undergo a compensatory expansion in response to the state of insulin resistance, where prolactin (PRL) plays a major role. Retinoblastoma protein (Rb) has been shown to critically regulate islet proliferation and function. The aim of the study was to explore the role of Rb in beta cell mass expansion during pregnancy. During pregnancy, expression of Rb, phospho-Rb (p-Rb), p107 and E2F1 increased, while p130 decreased in maternal islets. With PRL stimulation, induction of Rb expression occurred mainly in the nucleus while p-Rb was predominantly in the cytoplasm...
December 4, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/30510843/a-review-of-clinical-trials-mesenchymal-stem-cell-transplant-therapy-in-type-1-and-type-2-diabetes-mellitus
#5
REVIEW
Jang Cho, Matthew D'Antuono, Michael Glicksman, Jing Wang, Jacqueline Jonklaas
Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are widely prevalent metabolic diseases with differing pathologies. T1DM manifests due to autoimmune destruction of the pancreatic beta cells, resulting in a diminished secretion of insulin. T2DM originates from a state of insulin resistance, resulting in hyperglycemia and reduction in beta cell mass. Both diseases can cause severe health consequences. Despite the globally increasing prevalence of both T1DM and T2DM there remains to be a medically defined cure for either of these diseases...
2018: American Journal of Stem Cells
https://www.readbyqxmd.com/read/30510621/-polysiphonia-japonica-extract-attenuates-palmitate-induced-toxicity-and-enhances-insulin-secretion-in-pancreatic-beta-cells
#6
Seon-Heui Cha, Hyun-Soo Kim, Yongha Hwang, You-Jin Jeon, Hee-Sook Jun
Beta-cell loss is a major cause of the pathogenesis of diabetes. Elevated levels of free fatty acids may contribute to the loss of β -cells. Using a transgenic zebrafish, we screened ~50 seaweed crude extracts to identify materials that protect β -cells from free fatty acid damage. We found that an extract of the red seaweed Polysiphonia japonica (PJE) had a β -cell protective effect. We examined the protective effect of PJE on palmitate-induced damage in β -cells. PJE was found to preserve cell viability and glucose-induced insulin secretion in a pancreatic β -cell line, Ins-1, treated with palmitate...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/30509498/identification-of-rfx6-target-genes-involved-in-pancreas-development-and-insulin-translation-by-chip-seq
#7
Cheng Cheng, Jing Lu, Xi Cao, Fang-Yuan Yang, Jing-Yi Liu, Li-Ni Song, Han Shen, Chang Liu, Xiao-Rong Zhu, Jian-Bo Zhou, Jin-Kui Yang
Regulatory Factor X-box binding transcriptional factor 6 (Rfx6) plays an important role in the differentiation and development of pancreas in mammals. However, the direct target genes of Rfx6 to regulate this process were largely unknown. The present study aimed to investigate the function of Rfx6 on regulating pancreatic differentiation and development in a physiologically-relevant context. We performed the chromatin immunoprecipitation followed by the next generation sequencing analysis (ChIP-seq) using whole pancreatic tissue harvested from C57/BL6 adult mice to find target genes of Rfx6...
November 30, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30509117/gaba-promotes-%C3%AE-cell-proliferation-but-does-not-overcome-impaired-glucose-homeostasis-associated-with-diet-induced-obesity
#8
Ashley Untereiner, Shaaban Abdo, Alpana Bhattacharjee, Himaben Gohil, Farzaneh Pourasgari, Neke Ibeh, Mi Lai, Battsetseg Batchuluun, Anthony Wong, Nicholas Khuu, Ying Liu, Dana Al Rijjal, Neil Winegarden, Carl Virtanen, Beverley A Orser, Over Cabrera, Gabor Varga, Jonathan Rocheleau, Feihan F Dai, Michael B Wheeler
γ-Aminobutyric acid (GABA) administration has been shown to increase β-cell mass, leading to a reversal of type 1 diabetes in mice. Whether GABA has any effect on β cells of healthy and prediabetic/glucose-intolerant obese mice remains unknown. In the present study, we show that oral GABA administration ( ad libitum) to mice indeed increased pancreatic β-cell mass, which led to a modest enhancement in insulin secretion and glucose tolerance. However, GABA treatment did not further increase insulin-positive islet area in high fat diet-fed mice and was unable to prevent or reverse glucose intolerance and insulin resistance...
December 3, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30508415/high-glucose-alters-fetal-rat-islet-transcriptome-and-induces-progeny-islet-dysfunction
#9
Jose Jaime Casasnovas, Yunhee Jo, Xi Rao, Xiaoling Xuei, Mary E Brown, Kok Lim Kua
Offspring of diabetic mothers are susceptible to developing type 2 diabetes due to pancreatic islet dysfunction. However, the initiating molecular pathways leading to offspring pancreatic islet dysfunction are unknown. We hypothesized that maternal hyperglycemia alters offspring pancreatic islet transcriptome and negatively impacts offspring islet function. We employed an infusion model capable of inducing localized hyperglycemia in fetal rats residing in the left uterine horn, thus avoiding other factors involved in programming offspring pancreatic islet health...
December 1, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/30507613/human-islets-expressing-hnf1a-variant-have-defective-%C3%AE-cell-transcriptional-regulatory-networks
#10
Rachana Haliyur, Xin Tong, May Sanyoura, Shristi Shrestha, Jill Lindner, Diane C Saunders, Radhika Aramandla, Greg Poffenberger, Sambra D Redick, Rita Bottino, Nripesh Prasad, Shawn E Levy, Raymond D Blind, David M Harlan, Louis H Philipson, Roland W Stein, Marcela Brissova, Alvin C Powers
Using an integrated approach to characterize the pancreatic tissue and isolated islets from a 33-year-old with 17 years of type 1 diabetes (T1D), we found that donor islets contained β cells without insulitis and lacked glucose-stimulated insulin secretion despite a normal insulin response to cAMP-evoked stimulation. With these unexpected findings for T1D, we sequenced the donor DNA and found a pathogenic heterozygous variant in the gene encoding hepatocyte nuclear factor-1α (HNF1A). In one of the first studies of human pancreatic islets with a disease-causing HNF1A variant associated with the most common form of monogenic diabetes, we found that HNF1A dysfunction leads to insulin-insufficient diabetes reminiscent of T1D by impacting the regulatory processes critical for glucose-stimulated insulin secretion and suggest a rationale for a therapeutic alternative to current treatment...
December 3, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/30505337/coffee-consumption-is-positively-related-to-insulin-secretion-in-the-shanghai-high-risk-diabetic-screen-shids-study
#11
Fei Gao, Yinan Zhang, Sheng Ge, Huijuan Lu, Ruihua Chen, Pingyan Fang, Yixie Shen, Congrong Wang, Weiping Jia
Background: It has been proved that coffee consumption was associated with a lower risk of type 2 diabetes mellitus. But the benefit effect of coffee on hyperglycemia in Chinese population was largely unknown. Besides, the relationship of coffee intake and diabetic pathogenesis was still unclear. Methods: The study population was selected from the Shanghai High-Risk Diabetic Screen (SHiDS) project. A total of 1328 individuals over 18 years of age who have the information of coffee intake were enrolled in the study from 2012 to 2016...
2018: Nutrition & Metabolism
https://www.readbyqxmd.com/read/30504925/modelling-the-endocrine-pancreas-in-health-and-disease
#12
REVIEW
Mostafa Bakhti, Anika Böttcher, Heiko Lickert
Diabetes mellitus is a multifactorial disease affecting increasing numbers of patients worldwide. Progression to insulin-dependent diabetes mellitus is characterized by the loss or dysfunction of pancreatic β-cells, but the pathomechanisms underlying β-cell failure in type 1 diabetes mellitus and type 2 diabetes mellitus are still poorly defined. Regeneration of β-cell mass from residual islet cells or replacement by β-like cells derived from stem cells holds great promise to stop or reverse disease progression...
November 30, 2018: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/30504219/improved-tol2-mediated-enhancer-trap-identifies-weakly-expressed-genes-during-liver-and-%C3%AE-cell-development-and-regeneration-in-zebrafish
#13
Yadong Zhong, Wei Huang, Jiang Du, Zekun Wang, Jianbo He, Lingfei Luo
The liver and pancreas are two major digestive organs, and among the different cell types in them, hepatocytes and the insulin-producing β cells have roles in both health and diseases. Accordingly, clinicians and researchers are very interested in the mechanisms underlying the development and regeneration of liver and pancreatic β cells. Gene and enhancer traps such as Tol2 transposon-based system are useful for identifying genes potentially involved in developmental processes in the zebrafish model. Here, we developed a strategy that combines a Tol2 -mediated enhancer trap and the Cre/loxP system by using loxP-flanked reporters driven by β cell- or hepatocyte-specific promoters and the upstream activating sequence (UAS)-driving Cre...
November 30, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30503750/transcriptional-heterogeneity-of-beta-cells-in-the-intact-pancreas
#14
Lydia Farack, Matan Golan, Adi Egozi, Nili Dezorella, Keren Bahar Halpern, Shani Ben-Moshe, Immacolata Garzilli, Beáta Tóth, Lior Roitman, Valery Krizhanovsky, Shalev Itzkovitz
Pancreatic beta cells have been shown to be heterogeneous at multiple levels. However, spatially interrogating transcriptional heterogeneity in the intact tissue has been challenging. Here, we developed an optimized protocol for single-molecule transcript imaging in the intact pancreas and used it to identify a sub-population of "extreme" beta cells with elevated mRNA levels of insulin and other secretory genes. Extreme beta cells contain higher ribosomal and proinsulin content but lower levels of insulin protein in fasted states, suggesting they may be tuned for basal insulin secretion...
November 22, 2018: Developmental Cell
https://www.readbyqxmd.com/read/30503261/%C3%AE-cell-replacement-after-gene-editing-of-a-neonatal-diabetes-causing-mutation-at-the-insulin-locus
#15
Shuangyu Ma, Ryan Viola, Lina Sui, Valentino Cherubini, Fabrizio Barbetti, Dieter Egli
Permanent neonatal diabetes mellitus (PNDM) can be caused by insulin mutations. We generated induced pluripotent stem cells from fibroblasts of a patient with PNDM and undetectable insulin at birth due to a homozygous mutation in the translation start site of the insulin gene. Differentiation of mutant cells resulted in insulin-negative endocrine stem cells expressing MAFA, NKX6.1, and chromogranin A. Correction of the mutation in stem cells and differentiation to pancreatic endocrine cells restored insulin production and insulin secretion to levels comparable to those of wild-type cells...
November 20, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/30502051/abnormal-brown-adipose-tissue-mitochondrial-structure-and-function-in-il10-deficiency
#16
José C de-Lima-Júnior, Gabriela F Souza, Alexandre Moura-Assis, Rodrigo S Gaspar, Joana M Gaspar, Andréa L Rocha, Danilo L Ferrucci, Tanes I Lima, Sheila C Victório, Ivan L P Bonfante, Claudia R Cavaglieri, José C Pareja, Sérgio Q Brunetto, Celso D Ramos, Bruno Geloneze, Marcelo A Mori, Leonardo R Silveira, Gesmar R S Segundo, Eduardo R Ropelle, Lício A Velloso
BACKGROUND: Inflammation is the most relevant mechanism linking obesity with insulin-resistance and metabolic disease. It impacts the structure and function of tissues and organs involved in metabolism, such as the liver, pancreatic islets and the hypothalamus. Brown adipose tissue has emerged as an important component of whole body energy homeostasis, controlling caloric expenditure through the regulation of non-shivering thermogenesis. However, little is known about the impact of systemic inflammation on the structure and function of brown adipose tissue...
November 27, 2018: EBioMedicine
https://www.readbyqxmd.com/read/30501589/impact-of-type-1-and-type-2-diabetes-mellitus-on-pancreas-transplant-outcomes
#17
Vinayak Rohan, David Taber, Arun Palanisamy, John Mcgillicuddy, Kenneth Chavin, Prabhakar Baliga, Charles Bratton
OBJECTIVES: Pancreas transplant improves quality of life and survival of patients irrespective of pretransplant C-peptide levels. Our objectives were to examine complications and outcomes in patients without measureable C-peptide (insulin-dependent type 1 diabetes mellitus) and carefully selected patients with measurable C-peptide (insulin-dependent type 2 diabetes mellitus) after pancreas transplant. MATERIALS AND METHODS: We conducted a retrospective analysis to examine the demographic, transplant factors, complications, and outcomes in patients with nondetectable pretransplant C-peptide (insulin-dependent type 1 diabetes mellitus) and patients with detectable pretransplant C-peptide (insulin-dependent type 2 diabetes mellitus)...
November 28, 2018: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/30499633/exendin-4-lys-27-pal-gastrin-xenin-8-gln-a-novel-acylated-glp-1-gastrin-xenin-hybrid-peptide-that-improves-metabolic-status-in-obese-diabetic-ob-ob-mice
#18
Annie Hasib, Ming T Ng, Neil Tanday, Sarah L Craig, Victor A Gault, Peter R Flatt, Nigel Irwin
BACKGROUND: Therapeutic benefits of peptide-based drugs is limited by rapid renal elimination. METHODS: Therefore, to prolong the biological action profile of the recently characterised triple-acting hybrid peptide, exendin-4/gastrin/xenin-8-Gln, a fatty-acid (C-16) has been covalently attached, creating exendin-4(Lys27 PAL)/gastrin/xenin-8-Gln. Exendin-4/gastrin and liraglutide/gastrin/xenin-8-Gln were also synthesised as direct comparator peptides. RESULTS: All hybrid peptides evoked significant concentration-dependent increases of insulin secretion from isolated murine islets and BRIN-BD11 cells...
November 30, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/30488666/fam3b-pander-functions-as-a-co-activator-of-foxo1-to-promote-gluconeogenesis-in-hepatocytes
#19
Yujing Chi, Yuhong Meng, Junpei Wang, Weili Yang, Zhe Wu, Mei Li, Di Wang, Fangfang Gao, Bin Geng, Lu Tie, Weiping Zhang, Jichun Yang
FAM3B, also known as PANcreatic DERived factor (PANDER), promotes gluconeogenesis and lipogenesis in hepatocytes. However, the underlying mechanism(s) still remains largely unclear. This study determined the mechanism of PANDER-induced FOXO1 activation in hepatocytes. In mouse livers and cultured hepatocytes, PANDER protein is located in both the cytoplasm and nucleus. Nuclear PANDER distribution was increased in the livers of obese mice. In cultured mouse and human hepatocytes, PANDER was co-localized with FOXO1 in the nucleus...
November 28, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/30484226/immunomodulatory-properties-and-potential-therapeutic-benefits-of-muse-cells-administration-in-diabetes
#20
Marcelo Javier Perone, María Laura Gimeno, Florencia Fuertes
It is well established the link between inflammation and the development of insulin resistance and pathogenesis of type 2 diabetes. Type 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β cells mediated by autoreactive T lymphocytes and pro-inflammatory agents. Therefore, developing new strategies to efficiently control dysregulated inflammation could have substantial benefits in the treatment of diabetes. Recently, a novel population of non-tumorigenic pluripotent stem cells, named multilineage-differentiating stress-enduring (Muse) cells, was discovered...
2018: Advances in Experimental Medicine and Biology
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