Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deletion of insulin-degrading enzyme (IDE) in mice causes accumulation of cerebral amyloid beta-protein (Abeta), hyperinsulinemia, and glucose intolerance. Together with genetic linkage and allelic association of IDE to Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2), these findings suggest that IDE hypofunction could mediate human disease. To date, no coding mutations have been found in the canonical isoform of IDE, suggesting that pathological mutations could exist in undiscovered exons or regulatory regions, including untranslated regions (UTRs). However, neither isoforms arising from alternative splicing nor the UTRs have been described. Here, we systematically characterize human IDE mRNAs, identify a novel splice form, and compare its subcellular distribution, kinetic properties, and ability to degrade Abeta to the known isoform. Six distinct human IDE transcripts were identified, with most of the variance attributable to alternative polyadenylation sites. In the novel spliceoform, an exon we designate "15b" replaces the canonical exon "15a", and the resultant variant is widely expressed. Subcellular fractionation, immunofluorescent confocal microscopy, and immunogold-electron microscopy reveal that the 15b-IDE protein occurs in both cytosol and mitochondria. Organelle targeting of both isoforms is determined by which of two translation start sites is used, and only those isoforms utilizing the second site regulate levels of secreted Abeta. 15b-IDE can exist as a heterodimer with the 15a isoform or as a homodimer. The apparent K(m) values of recombinant 15b-IDE for both insulin and Abeta are significantly higher and the k(cat) and catalytic efficiency markedly lower than those of 15a-IDE. In accord, cells coexpressing beta-amyloid precursor protein (APP) and 15b-IDE accumulated significantly more Abeta in their media than those expressing APP and 15a-IDE. Our results identify a novel, catalytically inefficient form of IDE expressed in brain and non-neural tissues and recommend novel regions of the IDE gene in which to search for mutations predisposing patients to AD and DM2.
 ...
PMID:Alternative splicing of human insulin-degrading enzyme yields a novel isoform with a decreased ability to degrade insulin and amyloid beta-protein. 1585 Mar 85

Prevalence of the Type 2 diabetes mellitus (DM2) has been rising in the whole word. It is assumed that before DM2 develops, patients undergo a stadium of impaired glucose tolerance (IGT) or they have impaired fasting glycaemia (IFG). The confirmed IFG or IGT represent strong predictors of DM2 manifestation and at the same time they are related with high cardiovascular risk, namely with IGT. Other significant risk factor (RF) of DM2 is the obesity and metabolic syndrome. Recent clinical studies have shown that some metabolic abnormalities, which precede development of DM2 can be positively influenced by the lifestyle changes, including improvement of the diet and increasing the physical activity. Such measures can prevent or at least to delay the development of type 2 diabetes mellitus and thus the development of cardiovascular diseases. Positive effect has also the administration of some drugs, already tested in clinical studies, namely glitasons, metromin, inhibitor of ACE, sartans and other.
 ...
PMID:[Contemporary prospects of prevention of type 2 diabetes mellitus]. 1588 94

The aim of this study was to evaluate the prevalence of type 2 diabetes mellitus (DM2) and impaired glucose tolerance (IGT) in obese children and adolescents and to examine insulin resistance and insulin secretion. We studied 427 asymptomatic obese patients. DM2 and IGT were diagnosed by an oral glucose tolerance test. Insulin resistance and P-cell function were assessed by using homeostasis model assessment (HOMA), insulin/glucose index (I/GI), fasting insulin and insulin sensitivity index (ISI-composite). Thirty patients showed IGT (7%) and seven had DM2 (1.6%). The mean age was 10.7 +/- 3.5 years, the diabetic group being significantly older than the normal group (p < 0.01). The mean body mass index was 30 +/- 5.3 kg/m2 without significant differences between groups. beta-Cell function declined significantly in the patients with IGT and DM2, and insulin resistance increased significantly. Given the rather high prevalence of glucose metabolism impairment, children with obesity should undergo glucose tolerance testing for appropriate therapeutic intervention.
 ...
PMID:Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in obese Argentinean children and adolescents. 1592 Nov 79

Hmong refugees with type 2 diabetes mellitus (DM2) have poor glycemic control. For Hmong adults with DM2, group visits were instituted at a community health center and evaluated for their influence on diabetes management. Pre- and postintervention measures of physical health, mental health, and behavior were collected on 39 participants (64% participation rate). Baseline characteristics and clinical outcomes of 39 group visit participants were compared with 22 Hmong DM2 adults who refused to participate and 216 nonparticipating Hmong DM2 adults from a local diabetes registry. Baseline characteristics were similar among the three groups. Although participants received good medical services and their mental health improved (p < 0.05), clinical outcomes did not significantly improve. Although group visits are feasible for providing medical services for Hmong adults with DM2, clinical outcomes remain outside of recommended targets. Addressing mental health in this population may be necessary before people can institute behavioral changes that improve diabetes management.
 ...
PMID:Group visits for Hmong adults with type 2 diabetes mellitus: a pre-post analysis. 1593 95

Liquid chromatography/mass spectrometry (LC/MS) followed by multivariate statistical analysis has been successfully applied to the plasma phospholipids metabolic profiling in type 2 diabetes mellitus (DM-2). Principal components analysis and partial least-squares discriminant analysis (PLS-DA) models were tested and compared in class separation between the DM2 and control. The application of an orthogonal signal correction filtered model highly improved the class distinction and predictive power of PLS-DA models. Additionally, unit variance scaling was also tested. With this methodology, it was possible not only to differentiate the DM2 from the control but also to discover and identify the potential biomarkers with LC/MS/MS. The proposed method shows that LC/MS combining with multivariate statistical analysis is a complement or an alternative to NMR for metabonomics applications.
 ...
PMID:Plasma phospholipid metabolic profiling and biomarkers of type 2 diabetes mellitus based on high-performance liquid chromatography/electrospray mass spectrometry and multivariate statistical analysis. 1598 16

In genetic epidemiological studies informative families are often oversampled to increase the power of a study. For a proband-family design, where relatives of probands are sampled, we derive the score statistic to test for clustering of binary and quantitative traits within families due to genetic factors. The derived score statistic is robust to ascertainment scheme. We considered correlation due to unspecified genetic effects and/or due to sharing alleles identical by descent (IBD) at observed marker locations in a candidate region. A simulation study was carried out to study the distribution of the statistic under the null hypothesis in small data-sets. To illustrate the score statistic, data from 33 families with type 2 diabetes mellitus (DM2) were analyzed. In addition to the binary outcome DM2 we also analyzed the quantitative outcome, body mass index (BMI). For both traits familial aggregation was highly significant. For DM2, also including IBD sharing at marker D3S3681 as a cause of correlation gave an even more significant result, which suggests the presence of a trait gene linked to this marker. We conclude that for the proband-family design the score statistic is a powerful and robust tool for detecting clustering of outcomes.
 ...
PMID:Score statistic to test for genetic correlation for proband-family design. 1599 66

Diabetic retinopathy is the leading cause of adult vision loss and blindness. The most important contributors to the development of diabetic retinopathy are hyperglycemia and hypoxemia that lead to increased vasopermeability, endothelial cell proliferation, and pathological neovascularization. In our previous studies, close relationship between proangiogenic activity of sera from type 2 diabetes mellitus patients (DM2) with background retinopathy, assessed in the in vivo serum-induced mouse cutaneous test (SIA), and VEGF and IL-18 serum concentration were observed. Moreover, it was clearly shown that IGF-1 might play an important role in the negative regulation of neoangiogenesis induced by DM2 patients' sera by diminishing the VEGF stimulatory effect. To confirm the observed phenomenon we evaluated the effect of DM2 patients' sera on the in vitro proliferative activity of human endothelial cells, which is critical for the sprouting and generation of new blood capillaries. Endothelial proliferative activity was significantly higher in the presence of sera from DM2 patients than from healthy controls (P<0.001), as estimated by the MTT test. Moreover, the examined sera from DM2 patients were characterized by increased IL-18 (P<0.05), diminished IGF-1 (P<0.02), and unchanged VEGF levels compared with those in controls. In conclusion, the present study showed a strong stimulatory effect of DM2 patients' sera on the proliferation of endothelial cells, which, along with the findings of our previous studies, proves that the described phenomenon is universal and valid for both animal and human endothelium.
 ...
PMID:In vitro angiomodulatory activity of sera from type 2 diabetic patients with background retinopathy. 1620 77

Cardiovascular disease (CVD) and Type 2 diabetes mellitus (DM2), once conceived as different entities, share common origins and pathways. Increased activity of the renin-angiotensin-aldosterone-system, insulin resistance, chronic low-grade inflammation and oxidative stress collectively contribute to endothelial dysfunction and atherosclerosis, which manifest clinically as CVD. Nowadays, it is possible to identify and intervene in high-risk populations even before the clinical diagnosis of DM2. The control of dietary patterns and increased physical activity is completely feasible, as well as the management of hypertension and dyslipidaemia. Pharmacological interventions targeted at blocking renin-angiotensin-aldosterone-system and sensitising to insulin have a role in the prevention of DM2 and CVD, and are avidly explored worldwide. In the near future, ongoing trials should provide data that will allow us to better treat patients with the cardiometabolic syndrome and diabetes in order to reduce CVD morbidity and mortality.
 ...
PMID:Insights into the emerging cardiometabolic prevention and management of diabetes mellitus. 1621 82

Type II diabetes mellitus (DM2) is associated with an increased risk of cognitive dysfunction and dementia. The increased risk of dementia concerns both Alzheimer's disease and vascular dementia. Although some uncertainty remains into the exact pathogenesis, several mechanisms through which DM2 may affect the brain have now been identified. First, factors related to the 'metabolic syndrome', a cluster of metabolic and vascular risk factors (e.g. dyslipidaemia and hypertension) that is closely linked to DM2, may be involved. A number of these risk factors are predictors of cerebrovascular disease, accelerated cognitive decline and dementia. Secondly, hyperglycaemia may be involved, through adverse effects of potentially 'toxic' glucose metabolites on the brain and its vasculature. Thirdly, insulin itself may be involved. Insulin can directly modulate synaptic plasticity and learning and memory, and disturbances in insulin signalling pathways in the periphery and in the brain have recently been implicated in Alzheimer's disease and brain aging. Insulin also regulates the metabolism of beta-amyloid and tau, the building blocks of amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer's disease. In this paper, the evidence for the association between DM2 and dementia and for each of these underlying mechanisms will be reviewed, with emphasis on the role of insulin itself.
 ...
PMID:Increased risk of Alzheimer's disease in Type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology? 1624 41

Hyperglycaemia increases inflammatory cytokine concentration in the blood. Elevated levels of interleukin-18 (IL-18), a cytokine belonging to the interleukin-1 (IL-1) family, were recently reported in patients with Type 2 diabetes mellitus (DM2) and nephropathy. The aim of the present work was an examination of IL-18 concentration in the sera of elderly DM2 patients with nonproliferative retinopathy and age-matched control people and an estimation whether this cytokine plays pro- or anti-angiogenic role in in vivo angiogenic activity of their sera in mice cutaneous angiogenesis test. Recombinant human IL-18 injected intradermally to murine skin induced significant neovascular reaction. DM2 patients sera contained higher concentration of IL-18 and induced stronger neovascular reaction in mice skin than did the sera of corresponding control people. Sera from both groups of people after neutralization with antihuman IL-18 antibodies lost substantial part of their angiogenic activity.
 ...
PMID:Increased interleukin-18 content and angiogenic activity of sera from diabetic (Type 2) patients with background retinopathy. 1626 Mar 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>