Abstract:
:Cyclic adenosine 5'diphosphate-ribose (cADPR) is thought to have a second messenger role in insulin secretion through mobilisation of Ca2+. As human lymphocyte antigen CD38 has both ADP-ribosyl cyclase and cADPR hydrolase activity, it may be important in glucose-induced insulin secretion in islets. Thirty one randomly selected Japanese patients with Type II diabetes mellitus who had first-degree and/or second-degree relative(s) with Type II diabetes mellitus were screened for mutations of this gene using single-stranded conformation polymorphism. Two variant patterns in exon 3 and exon 4 of the CD38 gene were identified. The variant in exon 3 resulted in an amino acid substitution from Arg140 (CGG) to Trp (TGG). The Arg140Trp mutation was observed in 4 of 31 patients, and allele frequencies were significantly different in patients and the control subjects (p = 0.004). One patient with this mutation has two missense mutations on beta cell/liver glucose transporter (GLUT2) gene; her mother, who has impaired glucose tolerance, also has this mutation on the CD38 gene and one missense mutation on the GLUT2 gene. Enzyme activity studies using COS-7 cells expressing the Arg140Trp mutation showed a reduction in ADP-ribosyl cyclase and cADPR hydrolase activity of around 50%. The Arg140Trp mutation on CD38 thus appears to contribute to the development of Type II diabetes mellitus via the impairment of glucose-induced insulin secretion in the presence of other genetic defects.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Yagui K,Shimada F,Mimura M,Hashimoto N,Suzuki Y,Tokuyama Y,Nata K,Tohgo A,Ikehata F,Takasawa S,Okamoto H,Makino H,Saito Y,Kanatsuka Adoi
10.1007/s001250051026subject
Has Abstractpub_date
1998-09-01 00:00:00pages
1024-8issue
9eissn
0012-186Xissn
1432-0428journal_volume
41pub_type
杂志文章相关文献
DIABETOLOGIA文献大全abstract::Plasma glucose control and arterial pressure were assessed in 28 Type 1 (insulin-dependent) diabetic patients with different degrees of micro-albuminuria. They were divided into two groups according to their urinary albumin excretion rate: a low micro-albuminuria group (n = 16) with albumin excretion ranging between 1...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00262209
更新日期:1984-06-01 00:00:00
abstract:AIMS/HYPOTHESIS:Obesity and fatty liver are commonly associated with type 2 diabetes, but the genetic and functional bases linking fatty liver with obesity and diabetes are largely unknown. Our aim was to investigate the association of fatty liver with obesity and other diabetes-related phenotypes and to define the gen...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-007-0700-6
更新日期:2007-08-01 00:00:00
abstract::An in vitro method for detecting IgE insulin antibody using the principle of the radioallergosorbent test (RAST) is described. In six patients with insulin allergy, the RAST values were higher than in normal persons or insulin-treated diabetics without insulin-allergy. No differences were observed between normal perso...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00429705
更新日期:1978-01-14 00:00:00
abstract:AIMS/HYPOTHESIS:Hyperinsulinaemia and insulin resistance, as well as low IGF-I, have been implicated in the pathogenesis of cardiovascular disease. Little is known about direct effects of IGF-I and insulin on human coronary artery smooth muscle cells (HCASMCs). Our aim was to characterise the expression and function of...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-005-1890-4
更新日期:2005-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:We examined features of the metabolic syndrome to see if they modified the risk of chronic diabetic complications in patients with Type II (non-insulin-dependent) diabetes mellitus. METHODS:A total of 85 randomly selected patients with the metabolic syndrome (WHO definition) were compared with 85 Type ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250100615
更新日期:2001-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:We examined the prevalence of islet autoantibodies and their relationship to glycaemic control over 10 years in patients diagnosed clinically with new-onset type 2 diabetes. METHODS:Patient clinical characteristics and autoantibody status were determined at entry to the UK Prospective Diabetes Study (U...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/s00125-005-1690-x
更新日期:2005-04-01 00:00:00
abstract::Insulin and somatostatin reportedly affect pancreatic acinar cell function via specific receptor binding. Theoretically peri-insular levels depend on the islet-acinar portal system, but the actual hormone levels have never been demonstrated. Rat pancreata were perfused anterogradely or retrogradely with 125I-insulin, ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00400628
更新日期:1995-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:Exposure to sunlight has the potential to suppress metabolic dysfunction and obesity. We previously demonstrated that regular exposure to low-doses of ultraviolet radiation (UVR) reduced weight gain and signs of diabetes in male mice fed a high-fat diet, in part via release of nitric oxide from skin. He...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-019-05022-5
更新日期:2020-01-01 00:00:00
abstract::Type 1 diabetes is an immune-mediated disease leading to almost total beta cell destruction and permanent exogenous insulin dependency. The appearance of clinical symptoms is preceded by an asymptomatic preclinical period, the duration of which is highly individual. The emergence of diabetes-associated autoantibodies ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-016-4147-5
更新日期:2017-01-01 00:00:00
abstract:AIMS/HYPOTHESIS:Diabetes is induced by multiple low doses of streptozotocin (MLD-STZ) in male mice of susceptible strains. In this model beta-cell injury and T-cell-mediated inflammatory reactions are induced. Probably, reactive oxygen species (ROS) participate in the destruction of beta cells. The effects of ROS can b...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050009
更新日期:2000-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:Hyperlipidaemia is an independent risk factor for the progression of diabetic nephropathy, but its molecular mechanism remains elusive. We investigated in mice how diabetes and hyperlipidaemia cause renal lesions separately and in combination, and the involvement of Toll-like receptor 4 (TLR4) in the pr...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2578-1
更新日期:2012-08-01 00:00:00
abstract::Glucose-induced cyclic (3H) AMP accumulation, insulin secretory responses and the metabolism of glucose were studied in pancreatic islets from Acomys cahirinus. 27.7 mmol/l of glucose stimulated neither islet cyclic (3H) AMP accumulation nor insulin release during the first 5 min of incubation. Stimulation by glucose ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00423150
更新日期:1979-01-01 00:00:00
abstract::To assess in vivo effects of antioxidants on vascular cell adhesion molecule (VCAM)-1 expression, circulating soluble VCAM-1 and intraerythrocytic reduced glutathione (GSH) and GSH disulphide (GSSG) concentrations were evaluated in non-insulin-dependent diabetic patients without complications (9 men, 6 women, 48 +/- 6...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s001250051082
更新日期:1998-11-01 00:00:00
abstract::We have recently shown that leptin mimicks insulin effects on glucose transport and glycogen synthesis through a phosphatidylinositol-3 (PI) kinase dependent pathway in C2C12 myotubes. The aim of the present study was to identify the signalling path from the leptin receptor to the PI-3 kinase. We stimulated C2C12 myot...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050832
更新日期:1997-11-01 00:00:00
abstract:AIMS/HYPOTHESIS:The benefits of moderate alcohol consumption for type 2 diabetes have been postulated to involve a mechanism of improved insulin sensitivity. Fetuin-A, which is known to inhibit insulin signalling, has emerged as a biomarker for diabetes risk. Alcohol consumption may influence circulating fetuin-A conce...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-013-3077-8
更新日期:2014-01-01 00:00:00
abstract::In the present study we investigated whether glomerular hyperfiltration and albuminuria in streptozotocin-induced diabetic nephropathy in male Wistar-Münich rats are associated with changes in the heparan sulphate content of the glomerular basement membrane. Rats with a diabetes mellitus duration of 8 months, treated ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00400090
更新日期:1995-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:Insulin control of glucose output is a major mechanism by which appropriate amounts of glucose are produced to supply energy to the central nervous system, without causing long-term increases of the plasma glucose concentration. It is hypothesised that the primary route by which insulin maintains contro...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s001250051474
更新日期:2000-07-01 00:00:00
abstract:AIMS/HYPOTHESIS:Insulin clearance may decline as an early mechanism compensating for deteriorating insulin sensitivity. However, no previous studies have investigated the association between subclinical inflammation or impaired fibrinolysis and insulin clearance. We examined the association between plasminogen activato...
journal_title:Diabetologia
pub_type: 杂志文章,多中心研究
doi:10.1007/s00125-012-2741-8
更新日期:2013-01-01 00:00:00
abstract::Under strict balance conditions we studied the effect of phenformin in 5 patients with diabetes mellitus. In all cases phenformin lowered the blood glucose values, and all patients showed a reduction of glycosuria. Contrary to other reports body weight increased during phenformin treatment. This was accompanied by pos...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00429918
更新日期:1975-10-01 00:00:00
abstract::The validity of the new diagnostic criteria for diabetes mellitus for Japanese subjects was assessed by the long-term prognosis of 501 patients, found in an epidemiological survey of 6,681 people in a Japanese town. Ten-year relative survival rates were examined in relation to the 50 g oral glucose tolerance test (ser...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00252627
更新日期:1981-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:G-protein-coupled receptor kinases (GRKs) play a key role in agonist-induced desensitisation of G-protein-coupled receptors (GPCRs) that are involved in metabolic regulation and glucose homeostasis. Our aim was to examine whether small peptides derived from the catalytic domain of GRK2 and -3 would amel...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-004-1444-1
更新日期:2004-07-01 00:00:00
abstract::QT intervals were measured over RR intervals ranging from 500 ms to 1000 ms in 13 normal male subjects, 13 male diabetic subjects without and 13 with autonomic neuropathy. There was a close linear relationship between QT and RR in all subjects. The slope of the regression line was significantly greater in the autonomi...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00418273
更新日期:1991-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:Pregnancies complicated by diabetes have a higher risk of adverse outcomes for mothers and children, including predisposition to disease later in life, e.g. metabolic syndrome and hypertension. We hypothesised that adverse outcomes from diabetic pregnancies may be linked to compromised placental functio...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-011-2132-6
更新日期:2011-07-01 00:00:00
abstract:AIMS/HYPOTHESIS:Glutamic acid decarboxylase autoantibodies (GADA) are the most frequent beta-cell-specific autoantibodies in type 1 diabetes and in latent autoimmune diabetes in adults (LADA). The autoimmune attack on pancreatic islet cells is associated with a T helper 1 cell (T(h)1) response, mainly represented by Ig...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-004-1558-5
更新日期:2004-11-01 00:00:00
abstract:AIMS/HYPOTHESIS:A key morphological feature of diabetic nephropathy is the accumulation and deposition of glycogen in renal tubular cells, known as Armanni-Ebstein lesions. While this observation has been consistently reported for many years, the molecular basis of these lesions remains unclear. METHODS:Using biochemi...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2805-9
更新日期:2013-03-01 00:00:00
abstract::We examined the origin of hypermethioninaemia in streptozotocin-diabetic rats. In rats administered streptozotocin over a range from 55 to 75 mg/kg, the dose of drug injected correlated directly with the plasma methionine concentration and inversely with the plasma insulin level. Although insulin administration preven...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00273913
更新日期:1984-10-01 00:00:00
abstract:AIM/HYPOTHESIS:The distinct metabolic properties of visceral and subcutaneous adipocytes may be due to inherent characteristics of the cells that are resident in each fat depot. To test this hypothesis, human adipocytes were differentiated in vitro from precursor stromal cells obtained from visceral and subcutaneous fa...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-007-0841-7
更新日期:2008-01-01 00:00:00
abstract::Circulating somatomedin-C/insulin-like growth factor-I levels are low in the diabetic rat and unresponsive to exogenous growth hormone. However, the nature of this defect in growth hormone action remains unclear and there is little data on insulin-like growth factor-I gene expression in response to other stimuli and i...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00277488
更新日期:1988-11-01 00:00:00
abstract:AIMS/HYPOTHESIS:The conversion of D-[3-(3)H]glucose to (3) HOH is currently measured to assess D-glucose utilisation. The validity of such a procedure was re-evaluated. METHODS:The conversion of D-[3-(3)H]glucose and D-[5-(3)H]glucose to (3) HOH was measured in rat pancreatic islets, parotid cells and erythrocytes. Th...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-002-0907-5
更新日期:2002-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:Perinatal exposure to bisphenol A (BPA), a widely distributed environmental endocrine disruptor, is associated with insulin resistance and diabetes in offspring. The underlying molecular mechanisms could involve epigenetics, as adverse effects induced by environmental exposure in early life are suggeste...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-013-2944-7
更新日期:2013-09-01 00:00:00