Abstract:
:The glycolytic enzyme glucokinase plays a primary role in the glucose-responsive secretion of insulin, and defects of this enzyme can cause NIDDM. As a step toward understanding the molecular basis of glucokinase (GK) gene regulation, we assessed the structure and regulation of the human GK gene beta-cell-type promoter. The results of reporter gene analyses using HIT-T15 cells revealed that the gene promoter was comprised of multiple cis-acting elements, including two primarily important cis-motifs: a palindrome structure, hPal-1, and the insulin gene cis-motif A element-like hUPE3. While both elements were bound specifically by nuclear proteins, it was the homeodomain-containing transcription factor insulin promoter factor 1 (IPF1)/STF-1/PDX-1 that bound to the hUPE3 site: IPF1, when expressed in CHO-K1 cells, became bound to the hUPE3 site and activated transcription. An anti-IPF1 antiserum used in gel-mobility shift analysis supershifted the DNA protein complex formed with the hUPE3 probe and nuclear extracts from HIT-T15 cells, thus supporting the involvement of IPF1 in GK gene activation in HIT-T15 cells. In contrast to the insulin gene, however, neither the synergistic effect of the Pan1 expression on the IPF1-induced promoter activation nor the glucose responsiveness of the activity was observed for the GK gene promoter. These results revealed some conservative but unique features for the transcriptional regulation of the beta-cell-specific genes in humans. Being implicated in insulin and GK gene regulations as a common transcription factor, IPF1/STF-1/PDX-1 is likely to play an essential role in maintaining normal beta-cell functions.
journal_name
Diabetesjournal_title
Diabetesauthors
Watada H,Kajimoto Y,Umayahara Y,Matsuoka T,Kaneto H,Fujitani Y,Kamada T,Kawamori R,Yamasaki Ydoi
10.2337/diab.45.11.1478subject
Has Abstractpub_date
1996-11-01 00:00:00pages
1478-88issue
11eissn
0012-1797issn
1939-327Xjournal_volume
45pub_type
杂志文章相关文献
DIABETES文献大全abstract::In an attempt to examine the role of an ACE gene insertion/deletion (I/D) polymorphism in type 2 diabetes, we conducted a case-control association study among 132 couple-pairs from northern China. The genotype frequencies for II, ID, and DD were 39.8, 39.8, and 20.3%, respectively, in the case group and 44.8, 44.8, an...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.6.1986
更新日期:2002-06-01 00:00:00
abstract::Antibodies to single stranded (SS-) and double stranded (DS-) DNA and RNA were determined by a passive microhemagglutination assay in sera from 80 children with juvenile-onset diabetes mellitus (JDM) and 129 children with asthma. The latter group was chosen for comparison with the JDM group because of their increased ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.11.1105
更新日期:1978-11-01 00:00:00
abstract::We investigated whether the effect of troglitazone on glucose disposal is associated with altered insulin signaling. Nondiabetic first-degree relatives of type 2 diabetic patients (age 30 +/- 2 years, BMI 30 +/- 1 kg/m(2); n = 20) were randomized in a double-blind manner to 3 months of troglitazone (200 mg/day) or pla...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diabetes.51.9.2691
更新日期:2002-09-01 00:00:00
abstract::Insulin levels in humans were measured by a new assay, the isotope dilution assay (IDA), based on stable isotope dilution mass spectrometry. A known amount of a deuterated analog of insulin was used as an internal standard and added to the serum samples before sample processing. After isolation by immunoaffinity chrom...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.1.44
更新日期:1997-01-01 00:00:00
abstract::In peripheral tissues, insulin signaling involves activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. In the hypothalamus, insulin functions with leptin as an afferent adiposity signal important for the regulation of body fat stores and hepatic glucose metabolism. To ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.2.227
更新日期:2003-02-01 00:00:00
abstract::The newly inbred Cohen diabetic rat is an exceptional experimental model of diet-induced type 2 diabetes mellitus that is the result of secondary inbreeding nearly 30 years after it originally had been established. Animals from the original colony were selectively inbred by stringent criteria for 10 additional generat...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.11.2521
更新日期:2001-11-01 00:00:00
abstract:OBJECTIVE:Antecedent hypoglycemia can blunt neuroendocrine and autonomic nervous system responses to next-day exercise in type 1 diabetes. The aim of this study was to determine whether antecedent increase of plasma cortisol is a mechanism responsible for this finding. RESEARCH DESIGN AND METHODS:For this study, 22 ty...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db09-0382
更新日期:2009-09-01 00:00:00
abstract::To test whether treatment with aminoguanidine, a drug known to prevent cross-linking between glycated proteins, is effective in improving reduced erythrocyte deformability in diabetes, we studied a group (n = 6) of ALX-induced long-term (12.7 +/- 2.2 mo of hyperglycemia) diabetic New Zealand white rabbits before and a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.42.4.590
更新日期:1993-04-01 00:00:00
abstract:OBJECTIVE:Insulin resistance in skeletal muscle is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). However, the molecular mechanisms underlying skeletal muscle insulin resistance and the insulin-sensitizing effect of thiazolidinediones in PCOS in vivo are less well characterized....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db07-0706
更新日期:2008-02-01 00:00:00
abstract::To investigate whether insulin reduces platelet aggregability through a modulation of the guanosine-3',5'-cyclic monophosphate (cGMP) concentrations, we determined by a radioimmunoassay the cGMP values in the platelet-rich plasma (PRP) obtained from 17 healthy volunteers and incubated for 3 min with different concentr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.8.1015
更新日期:1994-08-01 00:00:00
abstract::To determine the effect of inhibition of gluconeogenesis on liver glycogen stores in patients with non-insulin-dependent diabetes mellitus (NIDDM) after a 3-day fast, 10% ethanol (EtOH) was administered intravenously to nine obese patients with NIDDM and six obese nondiabetic subjects. Rates of glucose appearance (3-[...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.2.256
更新日期:1994-02-01 00:00:00
abstract::Insulin replacement therapy in type 1 diabetes is imperfect because proper glycemic control is not always achieved. Most patients develop microvascular, macrovascular, and neurological complications, which increase with the degree of hyperglycemia. Engineered muscle cells continuously secreting basal levels of insulin...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.3.704
更新日期:2002-03-01 00:00:00
abstract::Adiponectin, an adipocyte protein important in insulin sensitization and cardioprotection, has a strong genetic component. We hypothesized that variants in the adiponectin gene (adipocyte collagen-domain containing [ACDC]) contribute to adiponectin levels in a biracial adolescent cohort. We genotyped 11 ACDC single nu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.55.02.06.db05-0446
更新日期:2006-02-01 00:00:00
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 ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.10.2603
更新日期:2004-10-01 00:00:00
abstract::In humans, low levels of growth hormone (GH) and its mediator, IGF-1, associate with hepatic lipid accumulation. In mice, congenital liver-specific ablation of the GH receptor (GHR) results in reductions in circulating IGF-1 and hepatic steatosis, associated with systemic insulin resistance. Due to the intricate relat...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0649
更新日期:2016-12-01 00:00:00
abstract::Precise timing of the teratogenic period in diabetic pregnancy is of clinical importance since correction of the glucose intolerance during this period may protect the offspring from malformations. An experimental approach to elucidate this problem with regard to skeletal development was made in groups of pregnant str...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.12.1141
更新日期:1983-12-01 00:00:00
abstract::Recent studies have identified that the activation of protein kinase C (PKC) and increased diacylglycerol (DAG) levels initiated by hyperglycemia are associated with many vascular abnormalities in retinal, renal, and cardiovascular tissues. Among the various PKC isoforms, the beta- and delta-isoforms appear to be acti...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.47.6.859
更新日期:1998-06-01 00:00:00
abstract::A reduced nocturnal fall in blood pressure (BP) and increased QT dispersion both predict an increased risk of cardiovascular events in diabetic as well as nondiabetic subjects. The relationship between these two parameters remains unclear. The role of diabetic autonomic neuropathy in both QT dispersion and circadian B...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.4.837
更新日期:2001-04-01 00:00:00
abstract::Low birth weight is a well-established risk factor for type 2 diabetes, but the risk at high birth weight levels remains uncertain. Potential sex differences in the associations are unexplored. We investigated whether sex influences the association of birth weight and adult type 2 diabetes, using a cohort of 113,801 m...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-0494
更新日期:2015-12-01 00:00:00
abstract:OBJECTIVE:The involvement of proangiogenic factors such as vascular endothelial growth factor as well as the therapeutic efficacy of angiogenesis inhibitors in early diabetic nephropathy has been reported. Vasohibin-1 (VASH-1) is a unique endogenous angiogenesis inhibitor that is induced in endothelial cells by proangi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-1790
更新日期:2009-10-01 00:00:00
abstract::Production of reactive oxygen species (ROS) is a key instigator of β-cell dysfunction in diabetes. The pleiotropic cytokine interleukin 6 (IL-6) has previously been linked to β-cell autophagy but has not been studied in the context of β-cell antioxidant response. We used a combination of animal models of diabetes and ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db17-1280
更新日期:2018-08-01 00:00:00
abstract::The inhibitory action of insulin and proinsulin on basal and glucagon-activated glycogenolysis was studied in cultured rat hepatocytes containing [14C]glycogen. Insulin or proinsulin given as sole hormones in the presence of 5 mM glucose decreased basal release of [14C]glucose from [14C]glycogen to 20%. Half-maximal e...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.36.5.551
更新日期:1987-05-01 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::Current pharmacological options for type 2 diabetes do not cure the disease. Despite the availability of multiple drug classes that modulate glycemia effectively and minimize long-term complications, these agents do not reverse pathogenesis, and in practice they are not selected to correct the molecular profile specif...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/dbi16-0069
更新日期:2017-07-01 00:00:00
abstract::Impaired skeletal muscle fatty acid oxidation has been suggested to contribute to insulin resistance and glucose intolerance. However, increasing muscle fatty acid oxidation may cause a reciprocal decrease in glucose oxidation, which might impair insulin sensitivity and glucose tolerance. We therefore investigated wha...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db12-0259
更新日期:2013-03-01 00:00:00
abstract::Culture of mesangial cells (MCs) in 5.6 vs. 30.0 mmol/l glucose for 3 weeks induced a sustained increase in protein kinase C (PKC) activity, transforming growth factor (TGF)-beta1 mRNA, bioactive TGF-beta, and collagen synthesis. Nitric oxide (NO), generated exogenously by the NO donor S-nitroso-N-acetyl, D,L-penicill...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.4.671
更新日期:1997-04-01 00:00:00
abstract::Several studies have indicated that insulin resistance, elevated blood pressure (BP), and dyslipidemia precede the onset of non-insulin-dependent diabetes mellitus (NIDDM). Little data, however, exist on the presence of renal disease in prediabetic subjects. We measured albumin excretion in a cross-sectional populatio...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.4.552
更新日期:1994-04-01 00:00:00
abstract::Accumulation of triosephosphates arising from high cytosolic glucose concentrations in hyperglycemia is the trigger for biochemical dysfunction leading to the development of diabetic nephropathy-a common complication of diabetes associated with a high risk of cardiovascular disease and mortality. Here we report that s...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.8.2110
更新日期:2003-08-01 00:00:00
abstract::Cellular cholesterol homeostasis is important for normal β-cell function. Disruption of cholesterol transport by decreased function of the ATP-binding cassette (ABC) transporter ABCA1 results in impaired insulin secretion. Mice lacking β-cell ABCA1 have increased islet expression of ABCG1, another cholesterol transpor...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1341
更新日期:2012-03-01 00:00:00
abstract::The association between clinical autonomic dysfunction and myocardial MIBG accumulation was investigated. The study groups comprised 6 male diabetic patients with autonomic neuropathy (ANP+ group), 6 male diabetic patients without autonomic neuropathy (ANP-group), and 6 male nondiabetic control subjects. The mean age ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.9.1069
更新日期:1992-09-01 00:00:00