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

Hyperandrogenemia predisposes an organism toward developing impaired insulin sensitivity. The aim of our study was to evaluate endocrine and metabolic effects during early allostasis induced by a fructose-rich diet (FRD) in normal (control; CT) and neonatal-androgenized (testosterone propionate; TP) female adult rats. CT and TP rats were fed either a normal diet (ND) or an FRD for 3 weeks immediately before the day of study, which was at age 100 days. Energy intake, body weight (BW), parametrial (PM) fat characteristics, and endocrine/metabolic biomarkers were then evaluated. Daily energy intake was similar in CT and TP rats regardless of the differences in diet. When compared with CT-ND rats, the TP-ND rats were heavier, had larger PM fat, and were characterized by basal hypoadiponectinemia and enhanced plasma levels of non-esterified fatty acid (NEFA), plasminogen activator inhibitor-1 (PAI-1), and leptin. FRD-fed CT rats, when compared with CT-ND rats, had high plasma levels of NEFA, triglyceride (TG), PAI-1, leptin, and adiponectin. The TP-FRD rats, when compared with TP-ND rats, displayed enhanced leptinemia and triglyceridemia, and were hyperinsulinemic, with glucose intolerance. The PM fat taken from TP rats displayed increase in the size of adipocytes, decrease in adiponectin (protein/gene), and a greater abundance of the leptin gene. PM adipocyte response to insulin was impaired in CT-FRD, TP-ND, and TP-FRD rats. A very short duration of isocaloric FRD intake in TP rats induced severe metabolic dysfunction at the reproductive age. Our study supports the hypothesis that the early-androgenized female rat phenotype is highly susceptible to developing endocrine/metabolic dysfunction. In turn, these abnormalities enhance the risk of metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease.
Obesity (Silver Spring) 2010 Mar
PMID:Parametrial adipose tissue and metabolic dysfunctions induced by fructose-rich diet in normal and neonatal-androgenized adult female rats. 1969 63

Obesity-induced inflammation contributes to the development of obesity-related metabolic disorders such as insulin resistance, type 2 diabetes, fatty liver disease, and cardiovascular disease. In this study, we investigated whether dietary capsaicin can reduce obesity-induced inflammation and metabolic disorders such as insulin resistance and hepatic steatosis. Male C57BL/6 obese mice fed a high-fat diet for 10 weeks received a supplement of 0.015% capsaicin for a further 10 weeks and were compared with unsupplemented controls. Glucose intolerance was estimated by glucose tolerance tests. Transcripts of adipocytokine genes and the corresponding proteins were measured by reverse transcription-PCR and enzyme-linked immunosorbent assay, and macrophage numbers were determined by flow cytometric analysis. Transient receptor potential vanilloid type-1 (TRPV-1), peroxisome proliferator-activated receptor (PPAR)-alpha, and PPARgamma coactivator-1alpha (PGC-1alpha) mRNAs were also measured by RT-PCR, and PPARalpha luciferase assays were performed. Dietary capsaicin lowered fasting glucose, insulin, leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice. Levels of tumor necrosis factor-alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-6 mRNAs and proteins in adipose tissue and liver decreased markedly, as did macrophage infiltration, hepatic triglycerides, and TRPV-1 expression in adipose tissue. At the same time, the mRNA/protein of adiponectin in the adipose tissue and PPARalpha/PGC-1alpha mRNA in the liver increased. Moreover, luciferase assays revealed that capsaicin is capable of binding PPARalpha. Our data suggest that dietary capsaicin may reduce obesity-induced glucose intolerance by not only suppressing inflammatory responses but also enhancing fatty acid oxidation in adipose tissue and/or liver, both of which are important peripheral tissues affecting insulin resistance. The effects of capsaicin in adipose tissue and liver are related to its dual action on PPARalpha and TRPV-1 expression/activation.
Obesity (Silver Spring) 2010 Apr
PMID:Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet. 1979 65

Visceral fat has been linked to insulin resistance and type 2 diabetes mellitus (T2DM); and emerging data links RBP4 gene expression in adipose tissue with insulin resistance. In this study, we examined RBP4 protein expression in omental adipose tissue obtained from 24 severely obese patients undergoing bariatric surgery, and 10 lean controls (4 males/6 females, BMI = 23.2 +/- 1.5 kg/m(2)) undergoing elective abdominal surgeries. Twelve of the obese patients had T2DM (2 males/10 females, BMI: 44.7 +/- 1.5 kg/m(2)) and 12 had normal glucose tolerance (NGT: 4 males/8 females, BMI: 47.6 +/- 1.9 kg/m(2)). Adipose RBP4, glucose transport protein-4 (GLUT4), and p85 protein expression were determined by western blot. Blood samples from the bariatric patients were analyzed for serum RBP4, total cholesterol, triglycerides, and glucose. Adipose RBP4 protein expression (NGT: 11.0 +/- 0.6; T2DM: 11.8 +/- 0.7; lean: 8.7 +/- 0.8 arbitrary units) was significantly increased in both NGT (P = 0.03) and T2DM (P = 0.005), compared to lean controls. GLUT4 protein was decreased in both NGT (P = 0.02) and T2DM (P = 0.03), and p85 expression was increased in T2DM subjects, compared to NGT (P = 0.03) and lean controls (P = 0.003). Regression analysis showed a strong correlation between adipose RBP4 protein and BMI for all subjects, as well as between adipose RBP4 and fasting glucose levels in T2DM subjects (r = 0.76, P = 0.004). Further, in T2DM, serum RBP4 was correlated with p85 expression (r = 0.68, P = 0.01), and adipose RBP4 protein trended toward an association with p85 protein (r = 0.55, P = 0.06). These data suggest that RBP4 may regulate adiposity, and p85 expression in obese-T2DM, thus providing a link to impaired insulin signaling and diabetes in severely obese patients.
Obesity (Silver Spring) 2010 Apr
PMID:Retinol-binding protein 4 (RBP4) protein expression is increased in omental adipose tissue of severely obese patients. 1981 14

The ability to accurately and noninvasively quantify fatty infiltration in organs such as the liver and the pancreas remains a critical component in understanding the link between obesity and its comorbidities such as type 2 diabetes and fatty liver disease. Single-voxel ((1)H) proton magnetic resonance spectroscopy (MRS) has long been regarded as the gold-standard noninvasive technique for such measurements. Recent advances in three-dimensional fat-water magnetic resonance imaging (MRI) methods have led to the development of rapid, robust, and quantitative approaches that can accurately characterize the proportion of fat and water content in underlying tissues across the full imaging volume, and hence entire organs of interest. One such technique is called IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation). This article prospectively compares three-dimensional (3D) IDEAL-MRI and single-voxel MRS in the assessment of hepatic (HFF) and pancreatic fat fraction (PFF) in 16 healthy subjects. MRS acquisitions took 3-4 min to complete whereas IDEAL acquisitions were completed in 20-s breath-holds. In the liver, there was a strong correlation (slope = 0.90, r(2) = 0.95, P < 0.001) between IDEAL and MRS-based fat fractions. In the pancreas, a poorer agreement between IDEAL and MRS was observed (slope = 0.32, r(2) = 0.51, P < 0.02). The discrepancy of PFF is likely explained by MRS signal contamination from surrounding visceral fat, presumably during respiratory motion. We conclude that IDEAL is equally accurate in characterizing hepatic fat content as MRS, and is potentially better suited for fat quantification in smaller organs such as the pancreas.
Obesity (Silver Spring) 2010 Apr
PMID:Comparison of fat-water MRI and single-voxel MRS in the assessment of hepatic and pancreatic fat fractions in humans. 1983 63

Although women with gestational diabetes mellitus (GDM) are advised to incorporate physical activity into their lifestyle in order to reduce their risk of developing type 2 diabetes (T2DM), it is recognized that new mothers face barriers to postpartum exercise. Thus, we sought to determine whether, following the diagnosis of GDM, women indeed alter their postpartum physical activity patterns, as compared to their peers without GDM. In this prospective observational cohort study, we assessed the physical activity patterns of 238 white women (58 with GDM, 180 without GDM) in the year before pregnancy and in the year following delivery, using the Baecke questionnaire, which evaluates the following three domains of physical activity: work, sport activity, and nonsport leisure-time activity. Before diagnosis with GDM, women reported lower pregravid sport (P = 0.010) and leisure-time activity (P = 0.013), compared to their peers without GDM. By 1 year postpartum, however, there were no longer significant differences between the GDM and non-GDM groups in either sport or leisure-time activity (P = 0.078 and P = 0.957, respectively). In particular, women with GDM significantly increased their leisure-time activity over the first year postpartum (F = 10.1, P = 0.002), whereas the non-GDM group did not (F = 0.00, P = 0.984). Indeed, on multiple linear regression analysis, GDM independently predicted an increase in leisure-time activity between 1 year pregravid and 1 year postpartum (t = 2.55, P = 0.012). Furthermore, this significant relationship persisted even after adjustment for the finding of prediabetes/diabetes at 3 months postpartum (t = 2.83, P = 0.005). In conclusion, women with GDM successfully increased their leisure-time activity in the first year postpartum, reflecting an element of lifestyle change following this diagnosis.
Obesity (Silver Spring) 2010 Jul
PMID:Gestational diabetes and postpartum physical activity: evidence of lifestyle change 1 year after delivery. 1983 73

A timely diagnosis of impaired glucose tolerance (IGT) is desirable in obesity. The oral glucose tolerance test (OGTT), the gold standard to diagnose this condition, may not be realistically performed in all patients due to discomfort, labor, and cost. The aim of this study was to assess whether one or more biochemical indexes measured in fasting conditions could be used to identify obese children at risk of IGT. A cohort of 563 white obese children and adolescents (M/F: 315/248; aged 4-17 years) was recruited and underwent anthropometric evaluation and OGTT. Anthropometric parameters, fasting plasma glucose (FPG), fasting serum insulin (FSI), and homeostasis model assessment of insulin resistance (HOMA(IR)) were tested in pursuit of a possible threshold to be used as a predictor of IGT. Thirty-seven children (6.9%) had IGT and one child (0.1%) had type 2 diabetes (T2D). FPG, FSI, and HOMA(IR) were all significantly higher in children with IGT than in children without IGT. Receiver-operating characteristic (ROC) curve analyses run for gender and puberty-adjusted FPG, FSI, and HOMA(IR) were all significant: area under the curve (95% confidence interval) equaled 0.68 (0.59-0.76), 0.66 (0.56-0.76), and 0.68 (0.59-0.78), respectively. The three parameters did not show significantly different sensitivity/specificity in the pooled population or in the gender/puberty subgroups. Thresholds varied among gender/puberty subgroups for FSI and HOMA(IR), but not for FPG, which showed a fixed threshold of 86 mg/dl. A gender/puberty independent cutoff of FPG may be considered a screening tool to narrow clinical indication to OGTT in obese white children and adolescents.
Obesity (Silver Spring) 2010 Jul
PMID:Fasting plasma glucose (FPG) and the risk of impaired glucose tolerance in obese children and adolescents. 1985 1

It is suggested that a large breast size among women may predict type 2 diabetes risk independent of BMI and waist circumference (WC). The purpose of this study was to determine the independent associations of breast volume with cardiometabolic risk factors and regional fat distribution. A total of 92 overweight or obese premenopausal women (age = 39.9 +/- 6.8 years) underwent full-body magnetic resonance imaging (MRI) for the assessment of breast volume, visceral adipose tissue (VAT), abdominal and lower-body subcutaneous AT (SAT), and intermuscular AT (IMAT), a 2-h oral glucose tolerance test (OGTT), and fasting phlebotomy for assessment of triglyceride, total, high-density lipoprotein-, and low-density lipoprotein-cholesterol levels. Breast volume was not associated with any of the cardiometabolic risk factors assessed (P > 0.05). However, VAT was consistently associated with a number of cardiometabolic risk factors (OGTT glucose, OGTT insulin, and triglyceride levels) after controlling for age, BMI, WC, breast volume, and the other AT depots. In univariate models, breast volume was positively associated with VAT, IMAT, and abdominal and lower-body SAT (P < 0.05). After controlling for age, BMI, and WC level, breast volume remained positively associated with VAT and IMAT (P < 0.05), such that women with the highest breast volume had approximately 1.1 and 1.3 kg more VAT and IMAT, respectively, but no more abdominal or lower-body SAT, by comparison to women with the smallest breast volume. Thus, the previously documented association between breast size and type 2 diabetes risk may be in part explained by excess VAT and/or IMAT deposition.
Obesity (Silver Spring) 2010 Jun
PMID:Breast volume is an independent predictor of visceral and ectopic fat in premenopausal women. 1985 12

Cross-sectional human studies have associated mitochondrial dysfunction to type 2 diabetes. We chose Zucker diabetic fatty (ZDF) rats as a model of progressive insulin resistance to examine whether intrinsic mitochondrial defects are required for development of type 2 diabetes. Muscle mitochondrial function was examined in 6-, 12-, and 19-week-old ZDF (fa/fa) and fa/+ control rats (n = 8-10 per group) using respirometry with pyruvate, glutamate, and palmitoyl-CoA as substrates. Six-week-old normoglycemic-hyperinsulinemic fa/fa rats had reduced mitochondrial fat oxidative capacity. Adenosine diphosphate (ADP)-driven state 3 and carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP)-stimulated state uncoupled (state u) respiration on palmitoyl-CoA were lower compared to controls (62.3 +/- 9.5 vs. 119.1 +/- 13.8 and 87.8 +/- 13.3 vs. 141.9 +/- 14.3 nmol O(2)/mg/min.). Pyruvate oxidation in 6-week-old fa/fa rats was similar to controls. Remarkably, reduced fat oxidative capacity in 6-week-old fa/fa rats was compensated for by an adaptive increase in intrinsic mitochondrial function at week 12, which could not be maintained toward week 19 (140.9 +/- 11.2 and 57.7 +/- 9.8 nmol O(2)/mg/min, weeks 12 and 19, respectively), whereas hyperglycemia had developed (13.5 +/- 0.6 and 16.1 +/- 0.3 mmol/l, weeks 12 and 19, respectively). This mitochondrial adaptation failed to rescue the progressive development of insulin resistance in fa/fa rats. The transition of prediabetes state toward advanced hyperglycemia and hyperinsulinemia was accompanied by a blunted increase in uncoupling protein-3 (UCP3). Thus, in ZDF rats insulin resistance develops progressively in the absence of mitochondrial dysfunction. In fact, improved mitochondrial capacity in hyperinsulinemic hyperglycemic rats does not rescue the progression toward advanced stages of insulin resistance.
Obesity (Silver Spring) 2010 Jun
PMID:Adaptations in mitochondrial function parallel, but fail to rescue, the transition to severe hyperglycemia and hyperinsulinemia: a study in Zucker diabetic fatty rats. 1987 88

The impact of obesity on cardiovascular disease (CVD) outcomes in patients with type 2 diabetes mellitus (T2DM) and established coronary artery disease (CAD) is controversial; whether BMI and/or waist circumference correlate with atherothrombotic risk factors in such patients is uncertain. We sought to evaluate whether higher BMI or waist circumference are associated with specific risk factors among 2,273 Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study participants with T2DM and documented CAD (baseline data, mean age 62 years, 66% non-Hispanic white, 71% men). Multiple linear regression models were constructed after adjusting for sex, age, race/ethnicity, US vs. non-US site, diabetes duration, exercise, smoking, alcohol, and relevant medication use. First-order partial correlations of BMI with risk factors after controlling for waist circumference and of waist circumference with risk factors after controlling for BMI were also evaluated. Ninety percent of the patients were overweight (BMI > or =25 kg/m(2)); 68% of men and 89% of women had high-risk waist circumference measures (> or =102 and > or =88 cm, respectively). BMI and waist circumference, in separate models, explained significant variation in metabolic (insulin, lipids, blood pressure (BP)) and inflammatory/procoagulation (C-reactive protein, PAI-1 activity and antigen, and fibrinogen) risk factors. In partial correlation analyses BMI was independently associated with BP and inflammatory/procoagulation factors, waist circumference with lipids, and both BMI and waist circumference with insulin. We conclude that, in cross-sectional analyses, both BMI and waist circumference, independently, are associated with increased atherothrombotic risk in centrally obese cohorts such as the BARI 2D patients with T2DM and CAD.
Obesity (Silver Spring) 2010 May
PMID:Relationships of obesity and fat distribution with atherothrombotic risk factors: baseline results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. 1987 98

Inhibition of fatty acid synthase (FASN) induces a rapid decline in fat stores in mice, suggesting a role for this enzyme in energy homeostasis. To investigate the potential role of FASN in the pathophysiology of human obesity, the FASN gene was sequenced in 48 German whites. Thirty-five single-nucleotide polymorphisms (SNPs) were identified. Eight SNPs representative for their linkage disequilibrium groups and the Val1483Ile (rs2228305) substitution were genotyped for subsequent association analyses in 1,311 adults from Germany. Further, the tagging SNPs were genotyped also in German childhood cohorts (738 schoolchildren, 205 obese children). Effects of genetic variation on FASN mRNA expression in visceral and subcutaneous adipose tissue from a subgroup of 172 subjects were analyzed. Several polymorphisms in the FASN (rs62078748, rs2229422, rs2229425, and rs17848939) were nominally associated with obesity in case-control studies including 446 obese subjects (BMI >or=30 kg/m(2)) and 389 lean controls (BMI <or=25 kg/m(2)) (adjusted P < 0.05). The strongest significant effect was found for rs2229422 (P = 1.3 x 10(-5) adjusted for age, sex, type 2 diabetes status), which was supported by associations with BMI, waist-to-hip ratio (WHR), fasting plasma insulin and glucose infusion rate (adjusted P < 0.05). Subjects with the Val1483Ile substitution appeared to be protected against obesity. In addition, rs17848939 was nominally significantly associated with the ratio of visceral/subcutaneous FASN mRNA expression (adjusted P = 0.04). No effect of genetic variation in FASN on obesity was found in children. In conclusion, our data indicate a role of FASN genetic variation in susceptibility to obesity in adults.
Obesity (Silver Spring) 2010 Jun
PMID:Effect of genetic variation in the human fatty acid synthase gene (FASN) on obesity and fat depot-specific mRNA expression. 1987 8


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