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 follow markedly different temporal courses in individual patients. Some individuals at high risk for developing IDDM, and presenting with impaired beta-cell function, appear to recover beta-cell function when followed prospectively. Moreover, after the clinical onset of IDDM, most patients experience a transitory period of improved insulin secretion. In vitro and in vivo experimental data suggest that beta-cells are indeed able to repair themselves after damage. Dispersed beta-cells or whole islets can survive and regain their function after a toxic assault. Furthermore, the abnormal insulin release and glucose oxidation of islets isolated from NOD mice during the prediabetic period is completely restored after 1 wk in tissue culture. Finally, treatment of NOD mice with monoclonal antibodies directed against infiltrating T-cells reverses the altered glucose metabolism of beta-cells. Note that beta-cell repair after exposure to different toxic agents can be enhanced both in vivo and in vitro. Potential enhancers of beta-cell repair are nicotinamide, glucose, protein-rich diets, and branched chain amino acids. A basic question that remains to be answered is the nature of the repair mechanisms triggered by beta-cells.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Diabetesjournal_title
Diabetesauthors
Eizirik DL,Sandler S,Palmer JPdoi
10.2337/diab.42.10.1383subject
Has Abstractpub_date
1993-10-01 00:00:00pages
1383-91issue
10eissn
0012-1797issn
1939-327Xjournal_volume
42pub_type
杂志文章,评审相关文献
DIABETES文献大全abstract::The use of HIV protease inhibitors (PIs) has been associated with several metabolic changes, including lipodystrophy, hyperlipidemia, and insulin resistance. The etiology of these adverse effects remains unknown. PIs have recently been found to cause acute and reversible inhibition of GLUT4 activity in vitro. To deter...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.4.937
更新日期:2002-04-01 00:00:00
abstract:OBJECTIVE:Digenic causes of human disease are rarely reported. Insulin via its receptor, which is encoded by INSR, plays a key role in both metabolic and growth signaling pathways. Heterozygous INSR mutations are the most common cause of monogenic insulin resistance. However, growth retardation is only reported with ho...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0787
更新日期:2009-12-01 00:00:00
abstract::Enterovirus infections, implicated in the pathogenesis of type 1 diabetes in a number of studies, may precipitate the symptoms of clinical diabetes and play a role in the initiation of the beta-cell damaging process. The aim of this study was to evaluate whether cellular immune responses to enterovirus antigens are ab...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.8.1308
更新日期:2000-08-01 00:00:00
abstract::The plasma and tissue concentration of ascorbic acid (AA) is reduced in diabetes. This study was designed to investigate the mechanism and significance of this phenomenon. The low plasma AA concentration of diabetic rats can be normalized by dietary AA supplement (20-40 mg/day), a dosage approximately equal to the max...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.3.359
更新日期:1988-03-01 00:00:00
abstract::Stimulation of cardiomyocyte guanosine 3',5'-cyclic monophosphate (cyclic GMP) via endothelial-derived nitric oxide (NO) is an important mechanism by which bradykinin and ACE inhibitors prevent hypertrophy. Endothelial NO dysfunction and cardiac hypertrophy are morbid features of diabetes not entirely prevented by ACE...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.9.2389
更新日期:2003-09-01 00:00:00
abstract::Hyperglycemia is a potent regulator of endogenous glucose production (EGP). Loss of this "glucose effectiveness" is a major contributor to elevated plasma glucose concentrations in type 2 diabetes (T2D). KATP channels in the central nervous system have been shown to regulate EGP in humans and rodents. We examined the ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-1256
更新日期:2020-06-01 00:00:00
abstract::Pancreatic islets contain enzyme activity which catalyzes the phosphorylation by MgATP of cardiac, skeletal, or smooth muscle myosin light chains. The enzyme is activated by calcium (Ka = 10 microM) and calmodulin (Ka = 2 nM) and inhibited by trifluoperazine (Ki = 10 microM), a known inhibitor of calmodulin and of ins...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.31.6.566
更新日期:1982-06-01 00:00:00
abstract::The effect of Ca2+ and calmodulin has been studied on adenylate cyclase activity in homogenates of rat islets of Langerhans. EGTA had a stimulatory effect on the enzyme in accord with the known inhibitory effect of Ca2+. In contrast, the addition of Ca2+ together with calmodulin is stimulatory and demonstrates the exi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.29.1.74
更新日期:1980-01-01 00:00:00
abstract::Neonatal female rat pups that were raised artificially on a high-carbohydrate (HC) milk formula during their suckling period developed hyperinsulinemia immediately, maintained chronic hyperinsulinemia in the postweaning period on laboratory diet, and developed obesity in adulthood. Pups (second-generation HC [2-HC]) b...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.4.984
更新日期:2003-04-01 00:00:00
abstract::One month following induction of diabetes with streptozotocin, one half of diabetic and control rats underwent unilateral nephrectomy. Subsequently, all animals were studied with respect to renal function and glomerular alterations of diabetes. Blood pressure levels were similar in all animals. Diabetic and control an...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.1.35
更新日期:1978-01-01 00:00:00
abstract::G(M), the muscle-specific glycogen-targeting subunit of protein phosphatase 1 (PP1) targeted to the sarcoplasmic reticulum, was proposed to regulate recovery of glycogen in exercised muscle, whereas mutation truncation of its COOH-terminal domain is known to be associated with type 2 diabetes. Here, we demonstrate dif...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.9.2221
更新日期:2003-09-01 00:00:00
abstract::We previously reported a syndrome of severe hyperinsulinemia and early-onset hypertension in three patients with dominant-negative mutations in the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR)-gamma. We now report the results of further detailed pathophysiological evaluation of these subj...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.4.910
更新日期:2003-04-01 00:00:00
abstract::To determine whether nonglucose nutrient-induced insulin secretion is impaired in pre-diabetes, subjects with impaired or normal fasting glucose were studied after ingesting either a mixed meal containing 75 g glucose or 75 g glucose alone. Despite comparable glucose areas above basal, glucose-induced insulin secretio...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1272
更新日期:2007-04-01 00:00:00
abstract::The adrenocortical steroid, dehydroepiandrosterone, has been shown previously to produce an antidiabetic effect in C57BL/KsJ db/db mice. Preliminary clinical data suggest that this steroid may enhance insulin sensitivity in humans. The therapeutic use of dehydroepiandrosterone may be limited by its androgenic action. ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.8.1105
更新日期:1993-08-01 00:00:00
abstract::Diabetic microangiopathy is a slowly progressive condition that usually manifests itself years after the onset of the carbohydrate-metabolism disturbance. It is a far more striking problem in some diabetics than in others. Differences in the pattern of its effect in several body systems suggest that the local vascular...
journal_title:Diabetes
pub_type: 杂志文章
doi:
更新日期:1976-01-01 00:00:00
abstract::Obesity is characterized by adipose tissue (AT) macrophage (ATM) accumulation, which promotes AT inflammation and dysfunction. Toll-like receptor 4 (TLR4) deficiency attenuates AT inflammation in obesity but does not impede the accumulation of ATMs. The purpose of the current study was to determine whether TLR4 defici...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1595
更新日期:2012-11-01 00:00:00
abstract::Bcl-2 mRNA expression was detected in rat blastocysts by in situ hybridization. The distribution of mRNA expression was rather heterogenous, with approximately 2% of high-expressing cells. In vitro exposure to 28 mmol/l D-glucose for 24 h resulted in a significant increase in the proportion of these cells compared wit...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.1.143
更新日期:2001-01-01 00:00:00
abstract::Hypoglycemia limits optimal glycemic control in type 1 diabetes mellitus (T1DM), making novel strategies to mitigate it desirable. We hypothesized that portal (Po) vein insulin delivery would lessen hypoglycemia. In the conscious dog, insulin was infused into the hepatic Po vein or a peripheral (Pe) vein at a rate fou...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0071
更新日期:2015-10-01 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::The effect of diabetes control on the activities of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), cholesterol acyltransferase (ACAT), and phenol 2-monooxygenase, the major enzymes regulating cholesterol metabolism, was determined in alloxan-induced diabetic rabbits, and the results obtained were correlated ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.39.5.626
更新日期:1990-05-01 00:00:00
abstract::Fasting hyperglycemia occurs when an excessive rate of endogenous glucose production (EGP) is not accompanied by an adequate compensatory increase in the rate of glucose disappearance (Rd). The situation following food ingestion is more complex as the amount of glucose that reaches the circulation for disposal is a fu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1166
更新日期:2016-05-01 00:00:00
abstract::Elevation of glucagon levels and increase in α-cell mass are associated with states of hyperglycemia in diabetes. Our previous studies have highlighted the role of nutrient signaling via mTOR complex 1 (mTORC1) regulation that controls glucagon secretion and α-cell mass. In the current studies we investigated the effe...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0440
更新日期:2021-02-01 00:00:00
abstract::The T-type Ca2+ channel is an important determinant of electrical activity and of Ca2+ influx in rat and human pancreatic beta-cells. We have identified and sequenced a cDNA encoding a T-type Ca2+ channel alpha1-subunit derived from INS-1, the rat insulin-secreting cell line. The sequence of the cDNA indicates a prote...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.1.59
更新日期:2000-01-01 00:00:00
abstract:OBJECTIVE:Genome-wide association studies have identified several variants within the MTNR1B locus that are associated with fasting plasma glucose (FPG) and type 2 diabetes. We refined the association signal by direct genotyping and examined for associations of the variant displaying the most independent effect on FPG ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-1660
更新日期:2009-06-01 00:00:00
abstract:OBJECTIVE:Reactive oxygen species (ROS) is one of most important factors in impaired metabolism secretion coupling in pancreatic β-cells. We recently reported that elevated ROS production and impaired ATP production at high glucose in diabetic Goto-Kakizaki (GK) rat islets are effectively ameliorated by Src inhibition,...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0021
更新日期:2011-01-01 00:00:00
abstract::Dietary methionine restriction (MR) produces a rapid and persistent remodeling of white adipose tissue (WAT), an increase in energy expenditure (EE), and enhancement of insulin sensitivity. Recent work established that hepatic expression of FGF21 is robustly increased by MR. Fgf21-/- mice were used to test whether FGF...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1212
更新日期:2017-04-01 00:00:00
abstract::Metformin is the most widely prescribed medication for the treatment of type 2 diabetes (T2D). However, gastrointestinal (GI) side effects develop in ~25% of patients treated with metformin, leading to the discontinuation of therapy in ~5% of cases. We hypothesized that reduced transport of metformin via organic catio...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-1388
更新日期:2015-05-01 00:00:00
abstract:OBJECTIVE:Pharmacogenomics is a key component of personalized medicine. The Israel Cardiovascular Events Reduction with Vitamin E Study, a prospective placebo-controlled study, recently demonstrated that vitamin E could dramatically reduce CVD in individuals with diabetes and the haptoglobin (Hp) 2-2 genotype (40% of d...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db08-0450
更新日期:2008-10-01 00:00:00
abstract::We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients. Subjects (n = 89) were randomized to vitamin E (1,800 IU daily) or placebo and were followed for 12 months. High-resolution ult...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diabetes.54.1.204
更新日期:2005-01-01 00:00:00
abstract::Studies from several laboratories suggest that oxidized LDL may play an important role in atherogenesis. Our group previously showed that treatment of aortic endothelial cells with low levels of MM-LDL caused increased expression of MCP-1, M-CSF, tissue factor, and a monocyte-binding protein. In these studies MM-LDL w...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.41.2.s74
更新日期:1992-10-01 00:00:00