Review of Diabetic Studies最新文献

{"title":"Enzyme Development for Human Islet Isolation: Five Decades of Progress or Stagnation?","authors":"Daniel Brandhorst,&nbsp;Heide Brandhorst,&nbsp;Paul R V Johnson","doi":"10.1900/RDS.2017.14.22","DOIUrl":"https://doi.org/10.1900/RDS.2017.14.22","url":null,"abstract":"<p><p>In comparison to procedures used for the separation of individual cell types from other organs, the process of human pancreatic islet isolation aims to digest the pancreatic exocrine matrix completely without dispersing the individual cells within the endocrine cell cluster. This objective is unique within the field of tissue separation, and outlines the challenge of islet isolation to balance two opposing priorities. Although significant progress has been made in the characterization and production of enzyme blends for islet isolation, there are still numerous areas which require improvement. The ultimate goal of enzyme production, namely the routine production of a consistent and standardized enzyme blend, has still not been realized. This seems to be mainly the result of a lack of detailed knowledge regarding the structure of the pancreatic extracellular matrix and the synergistic interplay between collagenase and different supplementary proteases during the degradation of the extracellular matrix. Furthermore, the activation of intrinsic proteolytic enzymes produced by the pancreatic acinar cells, also impacts on the chance of a successful outcome of human islet isolation. This overview discusses the challenges of pancreatic enzymatic digestion during human islet isolation, and outlines the developments in this field over the past 5 decades.</p>","PeriodicalId":34965,"journal":{"name":"Review of Diabetic Studies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115004/pdf/RevDiabeticStud-14-022.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35106049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Encapsulated Islet Transplantation: Where Do We Stand?","authors":"Vijayaganapathy Vaithilingam,&nbsp;Sumeet Bal,&nbsp;Bernard E Tuch","doi":"10.1900/RDS.2017.14.51","DOIUrl":"https://doi.org/10.1900/RDS.2017.14.51","url":null,"abstract":"<p><p>Transplantation of pancreatic islets encapsulated within immuno-protective microcapsules is a strategy that has the potential to overcome graft rejection without the need for toxic immunosuppressive medication. However, despite promising preclinical studies, clinical trials using encapsulated islets have lacked long-term efficacy, and although generally considered clinically safe, have not been encouraging overall. One of the major factors limiting the long-term function of encapsulated islets is the host's immunological reaction to the transplanted graft which is often manifested as pericapsular fibrotic overgrowth (PFO). PFO forms a barrier on the capsule surface that prevents the ingress of oxygen and nutrients leading to islet cell starvation, hypoxia and death. The mechanism of PFO formation is still not elucidated fully and studies using a pig model have tried to understand the host immune response to empty alginate microcapsules. In this review, the varied strategies to overcome or reduce PFO are discussed, including alginate purification, altering microcapsule geometry, modifying alginate chemical composition, co-encapsulation with immunomodulatory cells, administration of pharmacological agents, and alternative transplantation sites. Nanoencapsulation technologies, such as conformal and layer-by-layer coating technologies, as well as nanofiber, thin-film nanoporous devices, and silicone based NanoGland devices are also addressed. Finally, this review outlines recent progress in imaging technologies to track encapsulated cells, as well as promising perspectives concerning the production of insulin-producing cells from stem cells for encapsulation.</p>","PeriodicalId":34965,"journal":{"name":"Review of Diabetic Studies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115002/pdf/RevDiabeticStud-14-051.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35104438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Nexus of Stem Cell-Derived Beta-Cells and Genome Engineering.","authors":"Sara D Sackett,&nbsp;Aida Rodriguez,&nbsp;Jon S Odorico","doi":"10.1900/RDS.2017.14.39","DOIUrl":"https://doi.org/10.1900/RDS.2017.14.39","url":null,"abstract":"<p><p>Diabetes, type 1 and type 2 (T1D and T2D), are diseases of epidemic proportions, which are complicated and defined by genetics, epigenetics, environment, and lifestyle choices. Current therapies consist of whole pancreas or islet transplantation. However, these approaches require life-time immunosuppression, and are compounded by the paucity of available donors. Pluripotent stem cells have advanced research in the fields of stem cell biology, drug development, disease modeling, and regenerative medicine, and importantly allows for the interrogation of therapeutic interventions. Recent developments in beta-cell differentiation and genomic modifications are now propelling investigations into the mechanisms behind beta-cell failure and autoimmunity, and offer new strategies for reducing the propensity for immunogenicity. This review discusses the derivation of endocrine lineage cells from human pluripotent stem cells for the treatment of diabetes, and how the editing or manipulation of their genomes can transcend many of the remaining challenges of stem cell technologies, leading to superior transplantation and diabetes drug discovery platforms.</p>","PeriodicalId":34965,"journal":{"name":"Review of Diabetic Studies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115001/pdf/RevDiabeticStud-14-039.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35106050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variations in ADIPOR1 But Not ADIPOR2 are Associated With Hypertriglyceridemia and Diabetes in an Admixed Latin American Population.","authors":"Gustavo Mora-García,&nbsp;María S Ruiz-Díaz,&nbsp;Fabian Espitia-Almeida,&nbsp;Doris Gómez-Camargo","doi":"10.1900/RDS.2017.14.311","DOIUrl":"10.1900/RDS.2017.14.311","url":null,"abstract":"<p><strong>Background: </strong>Adiponectin is a hormone secreted by adipose tissue. It regulates glycolysis and lipolysis and is involved in the pathophysiology of diabetes and related disorders. Its activity is mainly mediated by the transmembrane receptors AdipoR1 and AdipoR2, which are encoded by ADIPOR1 (1q32.1) and ADIPOR2 (12p13.33) genes, respectively. In genetic association studies, single nucleotide polymorphisms (SNPs) in or near these genes have been associated with metabolic alterations. However, these relationships are still controversial.</p><p><strong>Aim: </strong>The aim of this work was to analyze possible associations between ADIPOR1/2 and diabetes and other metabolic disorders.</p><p><strong>Methods: </strong>A genetic association study was carried out in an admixed Latin American population. A sample of 200 adults was analyzed. Clinical and serum-biochemical characteristics were measured to diagnose obesity, abdominal obesity, hypertension, hyperglycemia, hypertriglyceridemia, low HDLc, insulin resistance (HOMA-IR), and diabetes. Three SNPs were genotyped in ADIPOR1 (rs10494839, rs12733285, and rs2275737) and ADIPOR2 (rs11061937, rs11612383, and rs2286383). For the association analysis, an additive model was assessed through logistic regression. An admixture adjustment was performed using a Monte-Carlo-Markov-Chain method, assuming a three-hybrid substructure (k = 3).</p><p><strong>Results: </strong>Two SNPs in ADIPOR1 were associated with diabetes: rs10494839 (OR = 3.88, adjusted p < 0.03) and rs12733285 (OR = 4.72, adjusted p < 0.03). Additionally, rs10494839 was associated with hypertriglyceridemia (OR = 2.16, adjusted p < 0.01). None of the SNPs in ADIPOR2 were associated with metabolic disorders.</p><p><strong>Conclusions: </strong>ADIPOR1 was consistently associated with diabetes and hypertriglyceridemia. This association was maintained even after adjusting for genetic stratification. There were no significant associations involving ADIPOR2.</p>","PeriodicalId":34965,"journal":{"name":"Review of Diabetic Studies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1900/RDS.2017.14.311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35559201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whey and Casein Proteins and Medium-Chain Saturated Fatty Acids from Milk Do Not Increase Low-Grade Inflammation in Abdominally Obese Adults.","authors":"Mette Bohl, Ann Bjørnshave, Søren Gregersen, Kjeld Hermansen","doi":"10.1900/rds.2016.13.148","DOIUrl":"10.1900/rds.2016.13.148","url":null,"abstract":"<p><strong>Background: </strong>Low-grade inflammation is involved in the development of diabetes and cardiovascular disease (CVD). Inflammation can be modulated by dietary factors. Dairy products are rich in saturated fatty acids (SFA), which are known to possess pro-inflammatory properties. However, different fatty acid compositions may exert different effects. Other components such as milk proteins may exert anti-inflammatory properties which may compensate for the potential negative effects of SFAs. Generally, the available data suggest a neutral role of dairy product consumption on inflammation.</p><p><strong>Aim: </strong>To investigate the effects of, and potential interaction between, a dietary supplementation with whey protein and milk fat, naturally enriched in medium-chain SFA (MC-SFA), on inflammatory markers in abdominal obese adults.</p><p><strong>Methods: </strong>The study was a 12-week, randomized, double-blinded, intervention study. Sixty-three adults were equally allocated to one of four groups which received a supplement of either 60 g/day whey or 60 g/day casein plus 63 g/day milk fat either high or low in MC-SFA content. Fifty-two subjects completed the study. Before and after the intervention, changes in plasma interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1RA), high-sensitive C-reactive protein (hsCRP), adiponectin, and monocyte chemoattractant protein-1 (MCP-1) were measured. Changes in inflammatory genes in the subcutaneous adipose tissue were also documented.</p><p><strong>Results: </strong>There were no differences in circulating inflammatory markers between protein types or fatty acid compositions in abdominally obese subjects, with the exception of an increase in adiponectin in response to high compared to low MC-SFA consumption in women. We found that combined dairy proteins and MC-SFAs influenced inflammatory gene expression in adipose tissue, while no effect was detected by dairy proteins or MC-SFA per se.</p><p><strong>Conclusion: </strong>Whey protein compared with casein and MC-SFA-enriched milk fat did not alter circulating markers of low-grade inflammation in abdominally obese subjects, except for an increase in circulating adiponectin in response to high MC-SFA in abdominally obese women.</p>","PeriodicalId":34965,"journal":{"name":"Review of Diabetic Studies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84720510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical and Biological Aspects of Extracts from Medicinal Plants with Antidiabetic Effects.","authors":"L. F. Gushiken, F. P. Beserra, A. L. Rozza, P. L. Bérgamo, D. A. Bergamo, C. H. Pellizzon","doi":"10.1900/RDS.2016.13.96","DOIUrl":"https://doi.org/10.1900/RDS.2016.13.96","url":null,"abstract":"Diabetes mellitus is a chronic disease and a leading cause of death in western countries. Despite advancements in the clinical management of the disease, it is not possible to control the late complications of diabetes. The main characteristic feature of diabetes is hyperglycemia, which reflects the deterioration in the use of glucose due to a faulty or poor response to insulin secretion. Alloxan and streptozotocin (STZ) are the chemical tools that are most commonly used to study the disease in rodents. Many plant species have been used in ethnopharmacology or to treat experimentally symptoms of this disease. When evaluated pharmacologically, most of the plants employed as antidiabetic substances have been shown to exhibit hypoglycemic and antihyperglycemic activities, and to contain chemical constituents that may be used as new antidiabetic agents. There are many substances extracted from plants that offer antidiabetic potential, whereas others may result in hypoglycemia as a side effect due to their toxicity, particularly their hepatotoxicity. In this article we present an updated overview of the studies on extracts from medicinal plants, relating the mechanisms of action by which these substances act and the natural principles of antidiabetic activity.","PeriodicalId":34965,"journal":{"name":"Review of Diabetic Studies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82716110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin Treatment Does Not Affect Testicular Size in Offspring Born to Mothers with Gestational Diabetes.","authors":"K. Tertti, J. Toppari, H. Virtanen, S. Sadov, T. Rönnemaa","doi":"10.1900/RDS.2016.13.e2015013","DOIUrl":"https://doi.org/10.1900/RDS.2016.13.e2015013","url":null,"abstract":"OBJECTIVES\u0000Studies in rodents suggest that metformin treatment during pregnancy may have harmful effects on testicular development in offspring. Our aim was to determine whether metformin treatment of gestational diabetes mellitus (GDM) affects testicular size in male offspring.\u0000\u0000\u0000METHODS\u0000We compared the testicular size in prepubertal boys born to mothers who participated in a randomized controlled trial (RCT) comparing metformin with insulin in the treatment of GDM. Twenty-five (42.4% of invited) and 27 (52.9% of invited) boys whose mothers had been treated with metformin or insulin, respectively, participated in the study. Testicular size was measured by a ruler, an orchidometer, and by ultrasonography at the age of 33 to 85 months.\u0000\u0000\u0000RESULTS\u0000The mean age of the boys was 60 months at the time of examination, and did not differ between the metformin and insulin group (p = 0.88). There was no difference in testicular size between the boys in the two groups (p always ≥ 0.40), and there were no significant differences in height, weight, BMI, BMI z-score, or waist-to-hip ratio (WHR) between the boys in the groups.\u0000\u0000\u0000CONCLUSIONS\u0000Prepubertal testicular size did not differ between offspring born to metformin-treated mothers and those born to insulin-treated mothers.","PeriodicalId":34965,"journal":{"name":"Review of Diabetic Studies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74101801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreas Transplantation of US and Non-US Cases from 2005 to 2014 as Reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR).","authors":"A. Gruessner, R. Gruessner","doi":"10.1900/RDS.2016.13.e2016002","DOIUrl":"https://doi.org/10.1900/RDS.2016.13.e2016002","url":null,"abstract":"This report is an update of pancreas and kidney transplant activities in the US and non-US region in two periods, 2005-2009 and 2010-2014. The aim of the report was to analyze transplant progress and success in the US compared to non-US countries, and to compare trends between the two periods. Between 2005-2009 and 2010-2014, the number of US pancreas transplants declined by over 20%, while the overall number of pancreas transplants performed outside the US has increased. The decline in US numbers is predominantly due to the decline in primary and secondary pancreas after kidney transplants (PAK). During the time period studied, the number of PAK transplants dropped by 50%. In contrast, the number of simultaneous pancreas/kidney transplants (SPK) declined by only 10%, and the number of pancreas transplants alone (PTA) by 20%. Over 90% of pancreas transplants worldwide were performed, with a simultaneous kidney transplant and excellent results. Transplant outcomes in SPK improved significantly because of a decrease in the rates of technical and immunologic graft loss. In 2010-2014 vs. 2005-2009, US SPK transplant patient survival at 1 year post-transplant increased from 95.7% to 97.4%, pancreas graft function from 88.3% to 91.3%, and kidney function from 93.6% to 95.5%. A significant improvement was also noted in PAK transplants. One-year patient survival increased from 96.4% to 97.9% and pancreas graft function from 81.0% to 86.0%. PTA 1-year patient survival remained constant at 97%, and pancreas 1-year graft survival improved from 81.0% to 85.7%. With the decline in the number of transplants, a change towards better pancreas donor selection was observed. In solitary transplants, the donors were primarily young trauma victims, and the pancreas preservation time was relatively short. A general tendency towards transplanting older recipients was noted. In 2010-2014 vs. 2005-2009, PTA recipients 50 years of age or older accounted for 32% vs. 22%, PAK for 28% vs. 22%, and SPK for 22% vs. 20%. This may be due to a relatively lower immunologic graft loss rate, especially in solitary transplants, which historically has been high in young recipients. The number of pancreas transplants in patients with type 2 diabetes and end-stage renal disease has increased, and accounted for 9% of all SPK recipients in 2010-2014.","PeriodicalId":34965,"journal":{"name":"Review of Diabetic Studies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84611387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Critical Evaluation of Existing Diabetic Foot Screening Guidelines.","authors":"C. Formosa, A. Gatt, N. Chockalingam","doi":"10.1900/RDS.2016.13.158","DOIUrl":"https://doi.org/10.1900/RDS.2016.13.158","url":null,"abstract":"AIM To evaluate critically the current guidelines for foot screening in patients with diabetes, and to examine their relevance in terms of advancement in clinical practice, improvement in technology, and change in socio-cultural structure. METHODS A structured literature search was conducted in Pubmed/Medline, CINAHL, Cochrane Register of Controlled Trials, and Google between January 2011 and January 2015 using the keywords '(Diabetes) AND (Foot Screening) AND (Guidelines)'. RESULTS Ten complete diabetes foot screening guidelines were identified and selected for analysis. Six of them included the full-process guidelines recommended by the International Diabetes Federation. Evaluation of the existing diabetes foot screening guidelines showed substantial variability in terms of different evidence-based methods and grading systems to achieve targets, making it difficult to compare the guidelines. In some of the guidelines, it is unclear how the authors have derived the recommendations, i.e. on which study results they are based, making it difficult for the users to understand them. CONCLUSIONS Limitations of currently available guidelines and lack of evidence on which the guidelines are based are responsible for the current gaps between guidelines, standard clinical practice, and development of complications. For the development of standard recommendations and everyday clinical practice, it will be necessary to pay more attention to both the limitations of guidelines and the underlying evidence.","PeriodicalId":34965,"journal":{"name":"Review of Diabetic Studies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90261109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benefits of Rosuvastatin in Cardiovascular Protection Remain Unclear After HOPE-3.","authors":"Yu-Hung Chang, Der-Wei Hwu, Wei-Pin Kao, Yau-Jiunn Lee","doi":"10.1900/RDS.2016.13.212","DOIUrl":"10.1900/RDS.2016.13.212","url":null,"abstract":"","PeriodicalId":34965,"journal":{"name":"Review of Diabetic Studies","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734220/pdf/RevDiabeticStud-13-212.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34798683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}