Abstract:
:Several recent reports claim the generation of insulin-producing cells from embryonic stem cells via the differentiation of progenitors that express nestin. Here, we investigate further the properties of these insulin-containing cells. We find that although differentiated cells contain immunoreactive insulin, they do not contain proinsulin-derived C-peptide. Furthermore, we find variable insulin release from these cells upon glucose addition, but C-peptide release is never detected. In addition, many of the insulin-immunoreactive cells are undergoing apoptosis or necrosis. We further show that cells cultured in the presence of a phosphoinositide 3-kinase inhibitor, which previously was reported to facilitate the differentiation of insulin(+) cells, are not C-peptide immunoreactive but take up fluorescein isothiocyanate-labeled insulin from the culture medium. Together, these data suggest that nestin(+) progenitor cells give rise to a population of cells that contain insulin, not as a result of biosynthesis but from the uptake of exogenous insulin. We conclude that C-peptide biosynthesis and secretion should be demonstrated to claim insulin production from embryonic stem cell progeny.
journal_name
Diabetesjournal_title
Diabetesauthors
Hansson M,Tonning A,Frandsen U,Petri A,Rajagopal J,Englund MC,Heller RS,Håkansson J,Fleckner J,Sköld HN,Melton D,Semb H,Serup Pdoi
10.2337/diabetes.53.10.2603subject
Has Abstractpub_date
2004-10-01 00:00:00pages
2603-9issue
10eissn
0012-1797issn
1939-327Xpii
53/10/2603journal_volume
53pub_type
杂志文章相关文献
DIABETES文献大全abstract::Evidence suggests that alterations of glucose and lipid homeostasis induced by obesity are associated with the elevation of endocannabinoid tone. The biosynthesis of the two main endocannabinoids, N-arachidonoylethanolamine and 2-arachidonoyl-glycerol, which derive from arachidonic acid, is influenced by dietary fatty...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1279
更新日期:2016-07-01 00:00:00
abstract::In type 1 diabetes, a lifelong autoimmune disease, T cells infiltrate the islets and the exocrine pancreas in high numbers. CD8+ T cells are the main cell type found in the insulitic lesion, and CD8+ T cells reactive against beta cell antigens have been detected in the periphery and in the pancreas of subjects with sh...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0908
更新日期:2021-01-07 00:00:00
abstract::This article seeks to determine whether factors related to autoimmunity risk remain significant after the initiation of two or more diabetes-related autoantibodies and continue to contribute to type 1 diabetes (T1D) risk among autoantibody-positive children in The Environmental Determinants of Diabetes in the Young (T...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-0261
更新日期:2017-12-01 00:00:00
abstract::This study examined the suitability of commercial U.S.P. insulin as a bacterial growth medium. Purified port insulin (Iletin II, Eli Lilly & Co., Indianapolis, Indiana) was inoculated with approximately 500,000 bacteria per ml of: (1) Staphylococcus epidermidis, (2) Staphylococcus aureus, or (3) Escherichia coli. All ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.1.36
更新日期:1982-01-01 00:00:00
abstract::Subjects with overt non-insulin-dependent diabetes mellitus (NIDDM) were studied in comparison to obese nondiabetic control subjects and patients with subclinical diabetes. Pancreatic insulin secretion rates were measured by deconvolution of peripheral C-peptide over a 24-h period while subjects consumed an isocaloric...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.7.871
更新日期:1994-07-01 00:00:00
abstract::MDL 29311, an analogue of probucol, administered to rats as a 1% dietary admixture for 2 wk before and 5 days after intravenous injection of 40 mg/kg of ALX significantly (P < 0.05) reduced plasma glucose (6.9 +/- 0.3 vs. 19.2 +/- 1.3 mM) and serum triglyceride (0.17 +/- 0.01 vs. 1.82 +/- 0.39 mM) levels in overnight-...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.8.1179
更新日期:1993-08-01 00:00:00
abstract::Somatostatin-like immunoreactivity (SLI) concentrations were determined in human peripheral plasma using affinity chromatography followed by radioimmunoassay. In normal subjects, fasting SLI ranged from 2.9 to 22.0 pg/ml with a mean +/- SE value of 10.2 +/- 2.1 pg/ml. In totally pancreatectomized or gastrectomized pat...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.30.6.471
更新日期:1981-06-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) has been suggested to play a role in the pathogenesis of diabetic vascular complications. In the present study, we investigated whether expression of monocyte chemoattractant protein-1 (MCP-1), a chemokine that has been proposed to recruit leukocytes to sites of inflammation, ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.5.1131
更新日期:1999-05-01 00:00:00
abstract::Inhibition of fatty acid synthase (FAS) induces a rapid decline in fat stores in mice, suggesting a role for this enzyme in energy homeostasis. The human FAS gene (FAS) maps to chromosome 17q25, a region previously shown to have suggestive linkage to adiposity in a genome-wide linkage scan for genetic determinants of ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.7.1915
更新日期:2004-07-01 00:00:00
abstract::We explored the role of reactive oxygen species (ROS) in the pathogenesis of muscle insulin resistance. We assessed insulin action in vivo with a hyperinsulinemic-euglycemic clamp in mice expressing a mitochondrial-targeted catalase (MCAT) that were fed regular chow (RC) or a high-fat diet (HFD) or underwent an acute ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1334
更新日期:2017-08-01 00:00:00
abstract::Secondary hyperlipidemia is a major cardiovascular risk factor in individuals with type 2 diabetes. Increased hepatic production of apolipoprotein B (apoB)-containing lipoproteins contributes to the elevated plasma levels, but the mechanism is poorly understood. Recent results have established that microsomal triglyce...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.4.1233
更新日期:2002-04-01 00:00:00
abstract::Ectopic lipids in peripheral tissues have been implicated in attenuating insulin action in vivo. The botanical extract of Artemisia dracunculus L. (PMI 5011) improves insulin action, yet the precise mechanism is not known. We sought to determine whether the mechanism by which PMI 5011 improves insulin signaling is thr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-0396
更新日期:2012-03-01 00:00:00
abstract::The vascular endothelial growth factor (VEGF) family of cytokines are important regulators of angiogenesis that have emerged as important targets for the treatment of obesity. While serum VEGF levels rise during obesity, recent studies using genetic models provide conflicting evidence as to whether VEGF prevents or ac...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1665
更新日期:2014-08-01 00:00:00
abstract:OBJECTIVE:Most pancreatic endocrine cells derive from Ptf1a-expressing progenitor cells. In humans, nonsense mutations in Ptf1a have recently been identified as a cause of permanent neonatal diabetes associated with pancreatic agenesis. The death of Ptf1a-null mice soon after birth has not allowed further insight into ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-1558
更新日期:2008-09-01 00:00:00
abstract:OBJECTIVE:Normal human myocardium switches substrate metabolism preference, adapting to the prevailing plasma substrate levels and hormonal milieu, but in type 1 diabetes, the myocardium relies heavily on fatty acid metabolism for energy. Whether conditions that affect myocardial glucose use and fatty acid utilization,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-1199
更新日期:2008-01-01 00:00:00
abstract::Islet antigens associated with type 1 diabetes include a recently identified protein tyrosine phosphatase-like molecule IA-2, which contains the intracellular fragment IA-2ic. To determine whether combinations of antibodies including those to IA-2 characterize and predict type 1 diabetes, we studied antibodies to IA-2...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.8.1270
更新日期:1997-08-01 00:00:00
abstract::There is growing interest in more widespread application of isolated islet transplantation for the treatment of type 1 diabetes; however, the sequelae of long-term islet residence within the liver are unknown. We report herein a consequence of intraportal islet transplantation, specifically the development of periport...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.7.1591
更新日期:2003-07-01 00:00:00
abstract::The significance of the portohepatic glucosensors for counterregulation in deep hypoglycemia (i.e., glycemia < 2.8 mM) was studied in chronically cannulated male mongrel dogs in the conscious state. A total of 16 experiments were carried out on 6 dogs using the liver clamp technique under hyperinsulinemic conditions (...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.8.1052
更新日期:1994-08-01 00:00:00
abstract::The antidiabetic thiazolidinediones, which include troglitazone and rosiglitazone, are ligands for the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-gamma and exert their antihyperglycemic effects by regulation of PPAR-gamma-responsive genes. We report here that PPAR-gamma activation by troglitazo...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.4.539
更新日期:2000-04-01 00:00:00
abstract::Understanding and manipulating pancreatic beta-cell proliferation is a major challenge for pancreas biology and diabetes therapy. Recent studies have raised the possibility that human beta-cells can undergo dedifferentiation and give rise to highly proliferative mesenchymal cells, which retain the potential to rediffe...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1654
更新日期:2007-05-01 00:00:00
abstract::These studies of a rat model for non-insulin-dependent diabetes mellitus (NIDDM) were performed to determine whether hyperglycemia occurs when capacity to synthesize insulin is exceeded. The neonatal streptozocin (STZ)-treated rat has acute hyperglycemia with marked destruction of pancreatic beta-cells, followed by gr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.34.3.235
更新日期:1985-03-01 00:00:00
abstract::Chronic high-fat feeding in rats induces profound whole-body insulin resistance, mainly due to effects in oxidative skeletal muscle. The mechanisms of this reaction remain unclear, but local lipid availability has been implicated. The aim of this study was to examine the influence of three short-term physiological man...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.12.2022
更新日期:1997-12-01 00:00:00
abstract::Several adrenoceptor subtypes are expressed in adipocytes, which together exert their influence on adipocyte metabolism. Therefore, we specifically examined the interactive effect of Trp64Arg (beta3) and Glu12/Glu9 (alpha2b) adrenoceptor (AR) polymorphisms on energy metabolism and body composition in healthy women wit...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.1.91
更新日期:2001-01-01 00:00:00
abstract::Most studies dealing with the pathogenesis of IDDM have emphasized the immune assault against beta-cells. In this perspective, we review the data that suggest that the beta-cell destruction of IDDM depends on a balance between beta-cell damage and repair. The progressive beta-cell damage leading to IDDM seems to follo...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.42.10.1383
更新日期:1993-10-01 00:00:00
abstract::The minor hemoglobins AIa, AIb, and AIc were studied in mice with either genetic or chemically induced diabetes. Hemoglobin AIc was elevated approximately twofold in all the phenotypically diabetic mice studied (C57BL/KsJ-db/db, C57BL/KsJ-ob/ob, C57BL/6J-db/db, and alloxan- and streptozotocin-treated mice). Elevation ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.25.1.1
更新日期:1976-01-01 00:00:00
abstract::A corpus of evidence suggests that T-helper type 1 (Th1)-dependent cellular immunity plays a pivotal role in the pathogenesis of autoimmune diabetes. This study was intended to find ways to prevent the development of NOD diabetes using a neutralizing anti-interleukin (IL)-12 antibody (C17.8) that inhibits Thl cell dif...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.12.1998
更新日期:2000-12-01 00:00:00
abstract:OBJECTIVE:Mutations in the insulin (INS) gene can cause neonatal diabetes. We hypothesized that mutations in INS could also cause maturity-onset diabetes of the young (MODY) and autoantibody-negative type 1 diabetes. RESEARCH DESIGN AND METHODS:We screened INS in 62 probands with MODY, 30 probands with suspected MODY,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-1467
更新日期:2008-04-01 00:00:00
abstract::Methylglyoxal (MGO), a major precursor for advanced glycation end products, is increased in diabetes. In diabetic rodents, inhibition of MGO prevents cardiovascular disease (CVD). Whether plasma MGO levels are associated with incident CVD in people with type 1 diabetes is unknown. We included 159 individuals with pers...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1578
更新日期:2017-08-01 00:00:00
abstract::Thiazolidinediones and exercise are both known to improve insulin action independently. Therefore, we determined whether combined therapy could normalize insulin action in the Zucker fatty (ZF) rat. Rats were fed troglitazone as a 0.2% food admixture over a 3-week exercise training period (treadmill running 5 days/wee...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.12.2154
更新日期:2000-12-01 00:00:00
abstract::Insulin-dependent diabetes mellitus (IDDM) involves the destruction of the insulin-producing cells in the islets of Langerhans. One possible cure is by transplanting the islet cells; however, transplanted islets, even between identical twins, are subject to autoimmune destruction by the disease process, resulting in d...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.1.114
更新日期:1992-01-01 00:00:00