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)

Given the increase in the incidence of insulin resistance, obesity, and type 2 diabetes in children and adolescents, it would be of paramount importance to assess quantitative indices of insulin secretion and action during a physiological perturbation, such as a meal or an oral glucose-tolerance test (OGTT). A minimal model method is proposed to measure quantitative indices of insulin secretion and action in adolescents from an oral test. A 7 h, 21-sample OGTT was performed in 11 adolescents. The C-peptide minimal model was identified on C-peptide and glucose data to quantify indices of beta-cell function: static phi(s) and dynamic phi(d) responsivity to glucose from which total responsivity phi was also measured. The glucose minimal model was identified on glucose and insulin data to estimate insulin sensitivity, S(I), which was compared to a reference measure, S(I)(ref), provided by a tracer method. Disposition indices, which adjust insulin secretion for insulin action, were then calculated. Indices of beta-cell function were phi(s) = 51.35 +/- 8.89 x 10(-9)min(-1), phi(d) = 1,392 +/- 258 x 10(-9), and phi = 82.09 +/- 17.70 x 10(-9)min(-1). Insulin sensitivity was S(I) = 14.19 +/- 2.73 x 10(-4), not significantly different from S(I)(ref) = 14.96 +/- 3.04 x 10(-4) dl/kg.min per microU/ml, and well correlated: r = 0.98, P < 0.0001, thus indicating that S(I) can be accurately measured from an oral test. Disposition indices were DI(s) = 1,040 +/- 201 x 10(-14) dl/kg/min(2) per pmol/l, DI(d) = 33,178 +/- 10,720 x 10(-14) dl/kg/min per pmol/l, DI = 1,844 +/- 522 x 10(-14) dl/kg/min(2) per pmol/l. Virtually the same minimal model assessment was obtained with a reduced 3 h, 9-sample protocol. OGTT interpreted with C-peptide and glucose minimal model has the potential to provide novel insight regarding the regulation of glucose metabolism in adolescents, and to evaluate the effect of obesity and interventions such as diet and exercise.
Obesity (Silver Spring) 2009 Feb
PMID:beta-Cell function and insulin sensitivity in adolescents from an OGTT. 1905 29

Low levels of adiponectin, a fat-derived hormone, are found to be correlated with coronary heart disease, type 2 diabetes, obesity, and insulin resistance. Conversely, high adiponectin levels are predictive of reduced coronary risk in long-term epidemiologic studies. However, the precise role of adiponectin in cardiomyocyte function is still not clear. This study was designed to examine the role of adiponectin in cardiac contractile function in the db/db model of diabetic obesity. Mechanical properties and intracellular Ca(2+) transients were evaluated in cardiomyocytes from lean control and db/db mice with or without adiponectin (10 microg/ml) treatment. Expression and phosphorylation of IRS-1, Akt, c-Jun, and c-Jun N terminal kinase (JNK) as well as markers of endoplasmic reticulum (ER) stress were evaluated using western blotting. Cardiomyocytes from db/db mice exhibited greater cross-sectional area, depressed peak shortening (PS), and maximal velocity of shortening/re-lengthening as well as prolonged duration of re-lengthening. Consistently, myocytes from db/db mice displayed a reduced electrically stimulated rise in intracellular Ca(2+) and prolonged intracellular Ca(2+) decay, which were abrogated by adiponectin treatment. Ratios between phosphorylated c-Jun and c-Jun as well as phosphorylated IRS-1 and IRS-1 were increased in db/db mice, the effect of which was attenuated by adiponectin. Levels of the phosphorylated ER stress makers PERK (Thr980), IRE-1, and eIF2alpha were significantly elevated in db/db mice compared with lean controls, although the effect was unaffected by adiponectin. Collectively, our data suggest that adiponectin improves cardiomyocyte dysfunction in db/db diabetic obese mice through a mechanism possibly related to c-Jun and IRS-1.
Obesity (Silver Spring) 2009 Feb
PMID:Adiponectin improves cardiomyocyte contractile function in db/db diabetic obese mice. 1905 32

Genome-wide association studies showed variation in insulin-like growth factor-2 binding protein 2 (IGF2BP2) to be associated with type 2 diabetes mellitus (T2DM). We examined a 20-kb region of IGF2BP2 for association with T2DM-related quantitative traits in Mexican American families of a proband with gestational diabetes mellitus (GDM) from the BetaGene study. We genotyped 14 single-nucleotide polymorphisms (SNPs) in 717 individuals from 146 families phenotyped by oral glucose tolerance test (OGTT), intravenous glucose tolerance tests (IVGTTs) with minimal model analysis, and dual-energy X-ray absorptiometry scan for percent body fat. Three SNPs and one SNP combination that captured the majority of the variation in the region were tested for association with T2DM-related quantitative traits using a variance components framework. After correction for multiple testing, rs11705701 showed association with percent body fat (P(ACT) = 0.041) with body fat decreasing approximately 1.5-2% per copy of the A allele. We next tested whether the interaction between rs11705701 and body fat was associated with T2DM-relative quantitative traits. rs11705701 was significantly associated with insulin sensitivity (Bonferroni P = 0.028) and marginally associated with OGTT 2-h insulin (Bonferroni P = 0.066) and disposition index (DI) (Bonferroni P = 0.072). We conclude that rs11705701 in IGF2BP2 is associated with body fat and this effect on body fat influences insulin resistance which may contribute to T2DM risk.
Obesity (Silver Spring) 2009 Apr
PMID:Variation in IGF2BP2 interacts with adiposity to alter insulin sensitivity in Mexican Americans. 1914 20

The aim of this study is to examine the association between obesity, metabolic syndrome, physical activity, and elevated gamma-glutamyltransferase (GGT) among Indigenous Australian adults who did not drink alcohol. A cross-sectional study of 791 Indigenous adults in rural North Queensland communities was conducted between 1999 and 2001. Measures included serum GGT, fasting glucose, cholesterol, and triglycerides; resting blood pressure, BMI, and waist circumference; and self-reported physical activity, alcohol intake, and tobacco smoking. Central obesity measured by waist circumference in this population was significantly associated with elevated GGT independently of lifestyle behaviors (Adjusted odds ratio (OR) = 2.7, 95% confidence interval (CI): 1.2-6.0). Metabolic syndrome (International Diabetes Federation definition) was also strongly associated with increased GGT (OR = 2.6, 95% CI: 1.5-4.6). Habitual physical activity may be slightly protective (OR = 0.9, 95% CI: 0.5-1.6) in this group, but this was not clearly demonstrated in this study. Prevention of type 2 diabetes and cardiovascular disease in this population should emphasize "waist loss" and metabolic health through dietary and other interventions.
Obesity (Silver Spring) 2009 Apr
PMID:gamma-Glutamyltransferase, obesity, physical activity, and the metabolic syndrome in indigenous Australian adults. 1914 21

Peroxisome proliferator-activated receptor gamma (PPARgamma) acts as a ligand-dependent transcription factor with a key role in mediating adipocyte differentiation and insulin sensitivity. Recently, we and others have shown that PPARgamma recruits the nuclear corepressors NCoR and silencing mediator for retinoid and thyroid hormone receptors (SMRT) to modulate adipogenesis. While the synthetic ligands for PPARgamma, the thiazolidinediones (TZD), are widely used in the treatment of type 2 diabetes mellitus, the biologically relevant endogenous PPARgamma ligand involved in adipogenesis remains unidentified. To further understand the role of ligand binding and corepressor interaction in PPARgamma-mediated adipogenesis, a mutation was introduced in the ligand-binding domain (LBD) of murine PPARgamma. PPARgammamut was created via two amino acid substitutions known to be major determinants of ligand selectivity among PPAR isotypes, H323Y and R288M. These mutations alter PPARgamma to the corresponding residues of the PPARalpha. Characterizing the in vitro functional properties of this mutant, we show that PPARgammamut preferentially responds to the PPARalpha agonist, WY-14643, over the TZD, pioglitazone. When expressed in 3T3-L1 preadipocytes using recombinant adenovirus, wild-type PPARgamma leads to adipocyte formation with both hormonal and TZD treatment. PPARgammamut blocks the upregulation of adipocyte-specific proteins by TZD, but surprisingly, not by standard hormonal inducers. Our data suggest that TZDs and the purported endogenous ligand do not interact in the same way with the PPARgamma LBD. We propose that the endogenous ligand has distinct properties that allow for promiscuity within the hydrophobic PPAR ligand-binding pocket, yet fosters appropriate cofactor recruitment and release to allow adipogenesis to proceed.
Obesity (Silver Spring) 2009 May
PMID:Altering PPARgamma ligand selectivity impairs adipogenesis by thiazolidinediones but not hormonal inducers. 1916 56

Obesity as well as its associated chronic diseases and adverse health consequences such as type 2 diabetes mellitus, dyslipidemia, hypertension, and coronary artery disease are afflicting middle-aged adults and an ever greater number of children globally. We planned to investigate new obesity-related factors using proteomics approaches in a randomly selected three high and three low BMI samples of Epstein-Barr-transformed B (EBV-B) lymphoblastoid cell lines prepared from two groups of young Japanese men with different BMI. To search novel obesity-related factors, comparisons of protein expressions between high and low BMI groups were carried out by two-dimensional gel electrophoresis (2-DE). Gene transcripts of proteasome subunits found out from 2-DE were further determined by quantitative real-time PCR. Results from proteomics approach showed that the expression of proteasome alpha subunit type 5 (PSMA5) was significantly lower in the high BMI male group than in those with low BMI (P < 0.05). To validate these results, we expanded the study to include 20 more men and used real-time PCR to quantify the mRNA expression level in their EBV-B cells. Both PSMA5 and PSMA2 of EBV-B cells showed negative correlation with BMI. Furthermore, the mRNA levels measured in the peripheral blood B lymphocytes for many proteasome subunits in 75 healthy men and women showed significant negative correlation with BMI in healthy men. Our findings suggest that proteasome expression may play a key role in obesity.
Obesity (Silver Spring) 2009 May
PMID:Proteasome subunits mRNA expressions correlate with male BMI: implications for a role in obesity. 1916 68

We aimed at determining which circulating forms of the adipokine adiponectin that increases lipid oxidation in liver and skeletal muscle are related to ectopic fat in these depots in humans. Plasma total-, high-molecular weight (HMW)-, middle-molecular weight (MMW)-, and low-molecular weight (LMW) adiponectin were quantified by an enzyme-linked immunosorbent assay. Their relationships with liver- and intramyocellular fat, measured using (1)H magnetic resonance spectroscopy, were investigated in 54 whites without type 2 diabetes. Liver fat, adjusted for gender, age, and total body fat, was associated only with HMW adiponectin (r = -0.35, P = 0.012), but not with total-, MMW-, or LMW adiponectin. In addition, subjects with fatty liver (liver fat > or =5.56%, n = 15) had significantly lower HMW- (P = 0.04), but not total-, MMW-, or LMW adiponectin levels, compared to controls (n = 39). Similarly, intramyocellular fat correlated only with HMW (r = -0.32, P = 0.039), but not with the other circulating forms of adiponectin. These data indicate that, among circulating forms of adiponectin, HMW is strongly related to ectopic fat, thus possibly representing the form of adiponectin regulating lipid oxidation in liver and skeletal muscle.
Obesity (Silver Spring) 2009 Feb
PMID:Adiponectin oligomers and ectopic fat in liver and skeletal muscle in humans. 1916 22

Pioglitazone, a thiazolidinedione (TZD) commonly used to treat type 2 diabetes, is associated with weight gain. Our study was designed to examine the effectiveness of three lifestyle-treatment programs of varying intensity on prevention of pioglitazone-induced weight gain and to measure the composition of the change in body weight. Thirty-nine adult overweight and obese subjects with type 2 diabetes mellitus were all treated with pioglitazone and prospectively randomized to one of three lifestyle-treatment programs with increasing level of intensity for 24 weeks. Body composition was measured by dual-energy X-ray absorptiometry (DXA), computed tomography, and multifrequency bioimpedance analysis both before and after therapy. Subjects demonstrated a "dose-response" effectiveness to three levels of lifestyle intervention to mitigate pioglitazone-induced weight gain. Mean (s.d.) weight change (kg) for the usual, standard, and intensive lifestyle groups were 4.9 +/- 4.9 (P = 0.005), 1.8 +/- 3.4 (P = 0.02), and -0.2 +/- 4.4 (NS) respectively. Total body fat increased 2.6 +/- 3.4 kg (P = 0.04) for the usual group and decreased for the intensive group -0.4 +/- 3.5 (NS). Change in abdominal subcutaneous and visceral adipose tissue (VAT) did not differ between groups, although ratio of visceral/subcutaneous fat decreased for the standard and intensive groups (NS). Both usual (P < 0.05) and standard care (NS) groups gained total body water. This is the first prospective, randomized study that demonstrates the beneficial effect of participation in a comprehensive lifestyle-weight-management program on lessening of weight gain associated with pioglitazone.
Obesity (Silver Spring) 2009 May
PMID:Prevention of weight gain in adult patients with type 2 diabetes treated with pioglitazone. 1918 65

This report provides a further analysis of the first year weight losses in the Look AHEAD (Action for Health in Diabetes) study and identifies factors associated with success. Participants were a total of 5,145 men and women with type 2 diabetes who were recruited at 16 sites and randomly assigned to an intensive lifestyle intervention (ILI) or a control condition, Diabetes Support and Education (DSE). During year 1, participants in ILI received comprehensive diet and physical activity counseling in a total of 42 group and individual sessions, compared with three educational sessions for DSE participants. As reported previously, at the end of the year, ILI participants lost 8.6% of initial weight, compared to 0.7% for DSE (P < 0.001). Within the ILI group, all racial/ethnic groups achieved clinically significant weight losses (>5.5%), although there were significant differences among groups. For the year, ILI participants attended an average of 35.4 treatment sessions and reported exercising a mean of 136.6 min/week and consuming a total of 360.9 meal replacement products. Greater self-reported physical activity was the strongest correlate of weight loss, followed by treatment attendance and consumption of meal replacements. The use of orlistat, during the second half of the year, increased weight loss only marginally in those ILI participants who had lost <5% of initial weight during the first 6 months and chose to take the medication thereafter as a toolbox option. The lifestyle intervention was clinically effective in all subsets of an ethnically and demographically diverse population.
Obesity (Silver Spring) 2009 Apr
PMID:One-year weight losses in the Look AHEAD study: factors associated with success. 1918 71

To characterize the influence of diet-, physical activity-, and self-esteem-related factors on insulin resistance in 8- 10-year-old African-American (AA) children with BMI greater than the 85th percentile who were screened to participate in a community-based type 2 diabetes mellitus (T2DM) prevention trial. In 165 subjects, fasting glucose- and insulin-derived values for homeostasis model assessment of insulin resistance (HOMA-IR) assessed insulin resistance. Body fatness was calculated following bioelectrical impedance analysis, and fitness was measured using laps from a 20-m shuttle run. Child questionnaires assessed physical activity, dietary habits, and self-esteem. Pubertal staging was assessed using serum levels of sex hormones. Parent questionnaires assessed family demographics, family health, and family food and physical activity habits. Girls had significantly higher percent body fat but similar anthropometric measures compared with boys, whereas boys spent more time in high-intensity activities than girls. Scores for self-perceived behavior were higher for girls than for boys; and girls desired a more slender body. Girls had significantly higher insulin resistance (HOMA-IR), compared with boys (P < 0.01). Adjusting for age, sex, pubertal stage, socioeconomic index (SE index), and family history of diabetes, multivariate regression analysis showed that children with higher waist circumference (WC) (P < 0.001) and lower Harter's scholastic competence (SC) scale (P = 0.044) had higher insulin resistance. WC and selected self-esteem parameters predicted insulin resistance in high-BMI AA children. The risk of T2DM may be reduced in these children by targeting these factors.
Obesity (Silver Spring) 2008 Sep
PMID:Baseline correlates of insulin resistance in inner city high-BMI African-American children. 1918 28


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