Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human islet amyloid polypeptide (hIAPP), a pancreatic islet protein of 37 amino acids, is the main component of islet amyloid, seen at autopsy in patients with type 2 diabetes mellitus (DM2). To investigate the roles of hIAPP and islet amyloid in DM2, we generated transgenic mice expressing hIAPP in their islet beta cells. In this study, we found that after a long-term, high-fat diet challenge islet amyloid was observed in only 4 of 19 hIAPP transgenic mice. hIAPP transgenic females exhibited severe glucose intolerance, which was associated with a downregulation of GLUT-2 mRNA expression. In isolated islets from hIAPP males cultured for 3 weeks on high-glucose medium, the percentage of amyloid containing islets increased from 5.5% to 70%. This ex vivo system will allow a more rapid, convenient, and specific study of factors influencing islet amyloidosis as well as of therapeutic strategies to interfere with this pathological process.
Exp Diabetes Res 2008
PMID:Human islet amyloid polypeptide transgenic mice: in vivo and ex vivo models for the role of hIAPP in type 2 diabetes mellitus. 1849 71

Chronic complications of diabetes are associated mainly with changes in major and small arterial vessels as well as in peripheral and autonomic fibers of the nervous system. For years it has been suggested that DM2 does not predispose to osteoporosis because bone mineral density (BMD) in DM2 patients is commonly normal or even increased. However, results of recent large cross-sectional studies have indicated that patients with DM2 have significantly increased risk of bone fractures, predominantly hip fractures (by 70%). Results of these studies suggest that the increased risk of fractures in DM2 is independent of BMD. In this group of patients is frequently associated the loss of vision caused by diabetic eye disease, peripheral neuropathy, arterial hypertension, orthostatic hypotonia (caused by autonomic neuropathy or/and by concomitant antihypertensive treatment), and ischemic disease of the brain, heart and lower extremities--conditions that predispose to falls. There are no specific methods of prophylaxis and treatment of osteoporosis associated with diabetes; therefore they should be based on widely accepted principles as in non-diabetic populations. It seems that in DM2 patients the most purposeful strategy could be the popularization of healthy attitudes aiming the elimination of unfavorable dietetic and environmental factors, such as low physical activity, smoking, and low vitamin D intake, as well as education against falls.
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PMID:[Does type 2 diabetes predispose to osteoporotic bone fractures?]. 1861 97

Insulin resistance (IR) and consequent hyperinsulinemia are hallmarks of Type 2 diabetes (DM2). Akt kinase (Akt) is an important molecule in insulin signaling, implicated in regulation of glucose uptake, cell growth, cell survival, protein synthesis, and endothelial nitric oxide (NO) production. Impaired Akt activation in insulin-sensitive tissues contributes to IR. However, Akt activity in other tissues, particularly those affected by complications of DM2, has been less studied. We hypothesized that hyperinsulinemia could have an impact on activity of Akt and its effectors involved in regulation of renal morphology and function in DM2. To address this issue, renal cortical Akt was determined in obese Zucker rats (ZO), a model of DM2, and lean controls (ZL). We also studied expression and phosphorylation of the mammalian target of rapamycin (mTOR) and endothelial NO synthase (eNOS), molecules downstream of Akt in the insulin signaling cascade, and documented modulators of renal injury. Akt activity was measured by a kinase assay with GSK-3 as a substrate. Expression of phosphorylated (active) and total proteins was measured by immunoblotting and immunohistochemistry. Renal Akt activity was increased in ZO as compared to ZL rats, in parallel with progressive hyperinsulinemia. No differences in Akt were observed in the skeletal muscle. Corresponding to increases in Akt activity, ZO rats demonstrated enhanced phosphorylation of renal mTOR. Acute PI3K inhibition with wortmannin (100 mug/kg) attenuated renal Akt and mTOR activities in ZO, but not in ZL rats. In contrast to mTOR, eNOS phosphorylation was similar in ZO and ZL rats, despite higher total eNOS expression. In conclusion, ZO rats demonstrated increases in renal Akt and mTOR activity and expression. However, eNOS phosphorylation did not follow this pattern. These data suggest that DM2 is associated with selective IR in the kidney, allowing pro-growth signaling via mTOR, whereas potentially protective effects mediated by eNOS are blunted.
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PMID:Renal activity of Akt kinase in obese Zucker rats. 1864 Oct 49

Toll-like receptor 4 (TLR4) is an important mediator of innate immunity. Type 2 diabetes (DM2) might be associated with changed innate immune response. We investigated whether the polymorphisms in the TLR4 gene are associated with diabetic retinopathy (DR). The study group of 864 patients with DM2 and 420 healthy individuals were genotyped. In the patient group 352 subjects were diagnosed with DR. Out of the remaining 512, 140 had DM2 for > or = 10 years but no DR. In the DM2 group 7.4% of patients were heterozygous for the Asp299Gly polymorphism compared with 6.5% controls. For Thr399Ile polymorphism there were 7.2% heterozygotes vs 6.2% controls. In most cases, the linkage disequilibrium between the minor alleles Gly299 and Ile399 was confirmed. Increased frequency of both heterozygous genotypes was observed in patients with retinopathy (11.2% for the Asp299Gly). The frequency of the G allele was significantly higher in patients with early onset retinopathy (n = 80) vs patients without DR (odds ratio = 5.0, and 95% confidence interval = 2.33-10.71). In contrast, in the entire retinopathy group, the odds ratio for the G allele was 1.88 (95% confidence interval = 0.93-3.79). In the multivariate logistic regression analysis, the G allele of Asp299Gly was an independent risk factor of early onset DR (p < 0.001). In conclusion, our results suggest an association between the Asp299Gly polymorphism of the TLR4 gene and early onset of DR in the DM2 patients. Thus the G allele may be a predictor of increased risk of retinopathy.
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PMID:Toll-like receptor 4 gene polymorphism and early onset of diabetic retinopathy in patients with type 2 diabetes. 1913 14

To assess the prevalence of balance symptoms in type-2 diabetes mellitus (DM2), at the first level of health care. Compared to 101 controls, 101 patients showed a higher frequency of all the symptoms investigated through a standardized questionnaire (p<0.01). In DM2 patients, balance symptoms should be intentionally investigated.
Diabetes Res Clin Pract 2009 Jun
PMID:Neuro-otologic symptoms in patients with type 2 diabetes mellitus. 1928 72

Type 2 diabetes mellitus (DM2) is a metabolic disorder characterized by relative insulin deficiency, insulin resistance and hyperglycemia. DM2 improperly managed can cause severe complications such as renal failure, blindness or arterial disease. In addition to serious complications due to DM2, in the past 20 years, several studies have demonstrated the association between DM2, insulin resistance and prothrombotic risk. In our study, we wanted to evaluate the correlation between coagulation factor levels, oxidative plasmatic levels and DM2. We considered 20 DM2 patients (65% women and 35% men), 40-65 years of age, who had a BMI between 25 and 40 kg/m2 and followed a diet with or without oral antidiabetic treatment and 20 controls, blood donors, 15 men (75%) and five women (25%), who had a BMI between 25 and 40 kg/m2 and their age was between 40 and 65 years. Plasmatic levels of oxidative stress markers (tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein) and coagulation markers (factors VII, VIII, IX, XI, XII, antithrombin III and fibrinogen) of both populations were analyzed following statistic criteria. The analyzed data of this study related to oxidative stress and coagulation factors proved that the differences observed between diabetic patients and controls were not statistically significant (P < 0.05) for tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein, factor VII and factor XI; conversely for factor VIII, factor IX, factor XII, antithrombin III and fibrinogen, the results gave a difference statistically significant (P < 0.01). In patients with DM2, factor VIII increased from 79 to 103%, factor IX from 88 to 103%, factor XII from 87 to 105% and finally, antithrombin III from 81 to 103%. Different results between literature and our study could be due to fact that the patients considered were in the early stage of diabetes when endothelial damage is absent and vascular complications are not clinically expressed. In this study, it is still shown that DM2 is a multifactor disease and its physiopathologic mechanisms are not completely known today.
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PMID:Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population. 1931 24

In circulating lymphomonocytes (CLM) of patients with Type 2 diabetes (DM2) pyruvate dehydrogenase (PDH), the major determinant of glucose oxidative breakdown, is affected by a cohort of alterations reflecting impaired insulin stimulated glucose utilization. The cohort is also expressed, although incompletely, in 40% of healthy young subjects with a DM2-family history (FH). Pregnancy restrains glucose utilization in maternal peripheral tissues to satisfy fetal requirements. Here we explore whether pregnant women develop the PDH alterations and, if so, whether there are differences between women with and without FH (FH+, FH-). Ten FH+ and 10 FH- were evaluated during pregnancy (12-14, 24-26, and 37-39 weeks) and 1 yr after (follow-up) for fasting plasma glucose and insulin as well as body mass index (BMI), and for the PDH alterations. Twenty FH- and 20 FH+ non-pregnant women served as controls. All FH+ and FH- controls exhibited normal clinical parameters and 8 FH+ had an incomplete cohort of PDH alterations. In FH- and FH+ pregnant women at 12-14 weeks clinical parameters were normal; from 24-26 weeks, with unvaried glucose, insulin and BMI rose more in FH- and only in the latter recovered the 12-14 weeks values at follow-up. In all FH-, the cohort of PDH alterations was incomplete at 24-26 weeks, complete at 37-39 weeks, and absent at follow-up but complete from 12-14 weeks including follow-up in all FH+. In FH-, the cohort is an acquired trait restricted to pregnancy signaling transiently reduced insulin-stimulated glucose utilization; in FH+, instead, it unveils the existence of an inherited DM2-related background these women all have, that is awakened by pregnancy and as such lastingly impairs insulin-stimulated glucose utilization.
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PMID:Pregnancy induces molecular alterations reflecting impaired insulin control over glucose oxidative pathways that only in women with a family history of Type 2 diabetes last beyond pregnancy. 1933 7

Many patients with type 2 diabetes mellitus (DM2) are at risk for micro and macro vascular complications, which could be observed in heavy smokers. Cigarette smoking increases the risk for type 2 diabetes incidence. Nicotine, acknowledged as the major pharmacologically active chemical in tobacco, is responsible for the association between cigarette smoking and development of diabetes. This minireview summarized recent studies on nicotine effects on insulin action and insulin secretion, indicating the impact of nicotine on type 2 diabetes development.
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PMID:Impact of cigarette smoking in type 2 diabetes development. 1943 55

The frequency and functionality of peripheral blood invariant (iNKT) cells and their subsets, as well as other regulatory T-cell subsets, were evaluated in patients with type 1A diabetes mellitus (DM1), Hashimoto's disease, and Graves' disease. In addition to healthy individuals (HC), patients with type 2 diabetes mellitus (DM2) were included as controls because this disease has a different physiopathology. A similar frequency of total iNKT cells, as well as their subsets, existed among HC and the different study groups. Similar results were reported when we compared the frequency of CD4(+)/CD25(high) T cells, CD8(+)/CD28(negative) T cells, and gamma-delta T cells among HC and study groups, whereas patients with DM2 exhibited a higher frequency of CD8(+)/CD28(negative) T cells compared with HC and DM1. Also, patients with DM2 exhibited a lower frequency of CD4(negative) and CD4(+) iNKT cells expressing tumor necrosis factor-alpha (TNF-alpha) than HC. We did not observe significant differences in the frequency of iNKT cells expressing interleukin-4 or interferon-gamma among study groups and controls. Our findings support a normal frequency and function of peripheral blood iNKT cells in different endocrine autoimmune diseases, but an abnormal expression of TNF-alpha by circulating iNKT cells from patients with DM2.
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PMID:Frequency and function of circulating invariant NKT cells in autoimmune diabetes mellitus and thyroid diseases in Colombian patients. 1948 Aug 56

Obesity is associated with increased risk for cardiovascular health problems including diabetes, hypertension, and stroke. These cardiovascular afflictions increase risk for cognitive decline and dementia, but it is unknown whether these factors, specifically obesity and Type II diabetes, are associated with specific patterns of brain atrophy. We used tensor-based morphometry (TBM) to examine gray matter (GM) and white matter (WM) volume differences in 94 elderly subjects who remained cognitively normal for at least 5 years after their scan. Bivariate analyses with corrections for multiple comparisons strongly linked body mass index (BMI), fasting plasma insulin (FPI) levels, and Type II Diabetes Mellitus (DM2) with atrophy in frontal, temporal, and subcortical brain regions. A multiple regression model, also correcting for multiple comparisons, revealed that BMI was still negatively correlated with brain atrophy (FDR <5%), while DM2 and FPI were no longer associated with any volume differences. In an Analysis of Covariance (ANCOVA) model controlling for age, gender, and race, obese subjects with a high BMI (BMI > 30) showed atrophy in the frontal lobes, anterior cingulate gyrus, hippocampus, and thalamus compared with individuals with a normal BMI (18.5-25). Overweight subjects (BMI: 25-30) had atrophy in the basal ganglia and corona radiata of the WM. Overall brain volume did not differ between overweight and obese persons. Higher BMI was associated with lower brain volumes in overweight and obese elderly subjects. Obesity is therefore associated with detectable brain volume deficits in cognitively normal elderly subjects.
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PMID:Brain structure and obesity. 1966 57


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