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)

We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFalpha, and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes.
Int J Exp Diabetes Res 2000
PMID:Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans with type 2 diabetes. 1146

Adiponectin, also referred to as AdipoQ or ACRP30, is a plasma protein produced and secreted exclusively from adipose tissue. The protein contains a collagen-like domain and a C1q-like globular domain. A protease-generated globular segment enhances fatty acid oxidation in muscles, thereby modulating lipid and glucose metabolism. Plasma adiponectin levels are inversely correlated with the severity of insulin resistance. A recent genome-wide scan study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. Here, we screened Japanese patients with type 2 diabetes and age- and BMI-matched nondiabetic control subjects for mutations in adiponectin gene. We identified four missense mutations (R112C, I164T, R221S, and H241P) in the globular domain. Among these mutations, the frequency of I164T mutation was significantly higher in type 2 diabetic patients than in age- and BMI- matched control subjects (P < 0.01). Furthermore, plasma adiponectin concentrations of subjects carrying I164T mutation were lower than those of subjects without the mutation. All the subjects carrying I164T mutation showed some feature of metabolic syndrome, including hypertension, hyperlipidemia, diabetes, and atherosclerosis. Our findings suggest that I164T mutation is associated with low plasma adiponectin concentration and type 2 diabetes.
Diabetes 2002 Jul
PMID:Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. 1208 69

Adiponectin (also called AdipoQ, gelatin-binding protein 28, Acrp30) is a novel adipocytokine with important metabolic effects. It is physiologically released from adipose tissue and circulates in serum as a hexamer and larger multimeric structure of high molecular weight. Serum level of the protein correlates with systemic insulin sensitivity. Recently adiponectin receptors AdipoR1 and AdipoR2 have been discovered by expression cloning. AdipoR1 is abundantly expressed in skeletal muscles, whereas AdipoR2 is predominantly expressed in the liver. Marked expression of mRNA for AdipoR1 and AdipoR2 has been lately reported in pancreatic beta cells. Both of the receptors activate AMPK and PPAR alpha metabolic pathways leading to an increase in fatty acid oxidation, glucose uptake and a decreased rate of gluconeogenesis, thus enhancing insulin sensitivity. Moreover effects of adiponectin mimic many metabolic actions of insulin such as augmenting blood flow and glucose disposal in NO-dependent manner. The precise mechanism of regulation of plasma adiponectin level is unknown. Recently the mechanism of transcriptional activation of adiponectin gene via PPAR gamma was described. Its level seems to be decreased by TNFalfa and beta-adrenergic agonists. Furthermore there is increasing evidence that some genetic variants in the adiponectin gene may be associated with its ethnical differences in level as well as its likely clinical consequences. Hipoadiponectynemia is associated with obesity, metabolic syndrome, diabetes type 2, cardiovascular disease, lipodystrophy in AIDS. In patients with chronic renal failure, anorexia nervosa plasma adlponectin level is increased. Weight loss and therapy with thlazolidinediones are proved to enhance endogenous adlponectin production in humans. In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and antiatherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, especially in individuals with low plasma levels of adiponectin.
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PMID:[Adiponectin--adipocytokine with a broad clinical spectrum]. 1523 Jan 53

Adiponectin, an adipocyte-secreted protein encoded by the ACDC gene (also known as APM1), has been shown to play an important role in the regulation of fatty acid and glucose metabolism in liver and muscle, where it modulates insulin sensitivity. Adiponectin enhances fatty acid oxidation in liver and muscle, thus reducing triglyceride content in these tissues. Moreover, it stimulates glucose utilization in muscle and inhibits glucose production by the liver, consequently decreasing blood glucose levels. Plasma adiponectin levels are positively correlated with insulin sensitivity in humans. Circulating adiponectin forms a wide range of multimers. Mutations in the ACDC gene result in an impaired multimerization and/or impaired secretion of adiponectin from adipocytes, both linked to the development of insulin resistance and type II diabetes. This review focuses on the molecular mechanisms underlying hypoadiponectinemia associated with the diabetic phenotype. We further discuss the more recent findings that implicate adiponectin multimer formation as an important feature of the biological function of this adipocyte-derived hormone.
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PMID:[Adiponectin gene polymorphism and protein dysfunction in the development of insulin resistance]. 1559 38

We performed a genome-wide linkage scan of plasma adiponectin levels in 569 nondiabetic participants in the Amish Family Diabetes Study. The highest logarithm of odds (LOD) score (2.13; P = 0.0009) occurred on chromosome 3q27 between markers D3S1602 and D3S1580, which flank APM1/ACDC, the adiponectin gene. The APM1 +2019 A/- insertion/deletion polymorphism in the 3' untranslated region (single nucleotide polymorphism [SNP] +2019; deletion allele frequency 0.30 in Amish) showed strong association with adiponectin levels in a dosage-dependent manner in a direction consistent with that reported in previous studies, with deletion heterozygosity increasing adiponectin levels by 1.3 +/- 0.5 microg/ml and deletion homozygosity increasing levels by 3.0 +/- 0.8 microg/ml (P < 0.0001). Two other SNPs, rs2241766 and rs1501299, showed moderate association. In a subset of 523 subjects genotyped for both SNP +2019 and rs2241766, including the APM1 SNP +2019 genotype as a covariate reduced the linkage signal at 3q27 by 1.26 LOD units (from 2.22 to 0.96) and including both SNPs reduced the signal by 1.51 LOD units (to 0.71). These findings, combined with a two-point LOD score of 2.35 for SNP +2019, provide evidence that variation in APM1 is responsible for linkage of adiponectin levels to 3q27 in the Old Order Amish.
Diabetes 2005 Jan
PMID:Linkage of plasma adiponectin levels to 3q27 explained by association with variation in the APM1 gene. 1561 38

Adiponectin is an abundant adipose tissue-derived protein with important metabolic effects. Plasma adiponectin levels are decreased in obese individuals, and low adiponectin levels predict insulin resistance and type 2 diabetes. Two variants in the adiponectin gene ACDC have been previously associated with plasma adiponectin levels, obesity, insulin resistance, and type 2 diabetes. To determine the role of genetic variation in ACDC in susceptibility to obesity and type 2 diabetes in Pima Indians, we screened the promoter, exons, and exon-intron boundaries of the gene to identify allelic variants. We identified 17 informative polymorphisms that comprised four common (minor allele frequency >15%) linkage disequilibrium clusters consisting of 1-4 variants each. We genotyped one representative polymorphism from each cluster in 1,338 individuals and assessed genotypic association with type 2 diabetes, BMI, serum lipid levels, serum adiponectin levels, and measures of insulin sensitivity and secretion. None of the ACDC variants were associated with type 2 diabetes, BMI, or measures of insulin sensitivity or secretion. One variant, single nucleotide polymorphism (SNP)-12823, was associated with serum adiponectin levels (P = 0.002), but this association explained only 2% of the variance of serum adiponectin levels. Our findings suggest that these common ACDC polymorphisms do not play a major role in susceptibility to obesity or type 2 diabetes in this population.
Diabetes 2005 Jan
PMID:Common Polymorphisms in the Adiponectin Gene ACDC Are Not Associated With Diabetes in Pima Indians. 1561 40

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 nucleotide polymorphisms (SNPs) in 631 non-Hispanic white and 553 African-American unrelated adolescents in grades 5-12 randomly selected from the Princeton School District Study. ACDC SNPs -11,391 (A allele), -10,068 (G allele), and +276 (T allele) were associated with higher adiponectin, adjusting for sex, puberty stage, BMI Z score, and waist Z score. Contiguous two-SNP haplotypes of promoter variants -11,391/-10,068 were significantly associated with adiponectin levels in whites and African Americans (P < 0.0001 and 0.03, respectively). Extended haplotypes from the promoter through the second intron (-11,391 to +349) strongly associated with adiponectin in whites (P = 6 x 10(-11)) and African Americans (P = 0.004), but haplotypes of first intron SNPs -4,521 to -657 did not (P > 0.2). Noncontiguous haplotypes or interactions between two-SNP (-11,391/-10,068) and three-SNP (+45, +276, and +349) haplotypes predicted adiponectin better than either region alone. Variants of ACDC are associated with adiponectin levels in whites and African Americans. Interactions between noncontiguous ACDC haplotypes strongly influence adiponectin levels, suggesting nonadditive and potentially cis relationships between these regions.
Diabetes 2006 Feb
PMID:Interactions between noncontiguous haplotypes in the adiponectin gene ACDC are associated with plasma adiponectin. 1644 90

Common single nucleotide polymorphisms (SNPs) in the ACDC adiponectin encoding gene have been associated with insulin resistance and type 2 diabetes in several populations. Here, we investigate the role of SNPs -11,377C > G, -11,391G > A, +45T > G, and +276G > T in 2,579 French Caucasians (1,229 morbidly obese and 1,350 control subjects). We found an association between severe forms of obesity and -11,377C (odds ratio 1.23, P = 0.001) and +276T (1.19, P = 0.006). Surprisingly, alternative alleles -11,377G and +276G have been previously reported as risk factors for type 2 diabetes. Transmission disequilibrium tests showed a trend in overtransmission (56.7%) of a risk haplotype 1((C))-1((G))-1((T))-2((T)) including -11,377C and +276T in 634 obesity trios (P = 0.097). Family-based analysis in 400 trios from the general population indicated association between obesity haplotype and higher adiponectin levels, suggesting a role of hyperadiponectinemia in weight gain. However, experiments studying the putative roles of SNPs -11,377C > G and +276G > T on ACDC functionality were not conclusive. In contrast, promoter SNP -11,391G > A was associated with higher adiponectin levels in obese children (P = 0.005) and in children from the general population (0.00007). In vitro transcriptional assays showed that -11,391A may increase ACDC activity. In summary, our study suggests that variations at the ACDC/adiponectin gene are associated with risk of severe forms of obesity. However, the mechanisms underlying these possible associations are not fully understood.
Diabetes 2006 Feb
PMID:ACDC/adiponectin polymorphisms are associated with severe childhood and adult obesity. 1644 93

The purpose of the present study was to assess the genetic risk for myocardial infarction (MI) in individuals with or without conventional coronary risk factors and thereby to contribute to the personalized prevention of MI in such individuals. The study population comprised 3483 unrelated Japanese individuals (1913 men, 1570 women). The 1192 subjects with MI (926 men, 266 women) and 2291 controls (987 men, 1304 women) either had or did not have conventional coronary risk factors, including hypertension, hypercholesterolemia, and diabetes mellitus. The genotypes for 164 polymorphisms of 137 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis and a stepwise forward selection procedure revealed that nine different polymorphisms were significantly (P<0.005) associated with MI among individuals with or without hypertension, hypercholesterolemia, or diabetes mellitus: 1018Cright curved arrow T of GP1BA, -108/3Gright curved arrow 4G of IPF1, 677Cright curved arrow T of MTHFR, and Gright curved arrow A of UTS2 in hypertensive individuals; 2445Gright curved arrow A of FABP2, -108/3Gright curved arrow 4G of IPF1, 677Cright curved arrow T of MTHFR, -11,377Cright curved arrow G of ACDC, Aright curved arrow G of AKAP10, 11,496Gright curved arrow A of F7, and 46Cright curved arrow T of F12 in individuals without hypercholesterolemia; 2445Gright curved arrow A of FABP2 in diabetic individuals; and -108/3Gright curved arrow 4G of IPF1 in nondiabetic individuals. Polymorphisms associated with MI may thus differ among individuals with different conventional coronary risk factors. Stratification of subjects on the basis of such risk factors may thus be important in order to achieve personalized prevention of MI with the use of genetic information.
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PMID:Association of gene polymorphisms with myocardial infarction in individuals with or without conventional coronary risk factors. 1714 57

To describe the function in terms of gene expression, and to find new factors, we performed random complementary DNA (cDNA) sequencing using a 3'-directed cDNA library that faithfully represents the composition of the messenger RNA (mRNA). Through a systematic search of active genes in adipose tissue, we found adiponectin, encoded by the most abundantly expressed gene in adipose tissue, termed apM1 (adipose most abundant gene transcript-1). Fat specific gene library generated in this Japanese Human Genome Project identified many other key molecules of this tissue such as leptin, PPARgamma and aP2 (adipocyte fatty acid binding protein, FABP4), in addition to apM1. Following 10 years, hundreds of clinical studies implicated the critical role of adiponectin in the metabolic syndrome. Also organized establishment of aP2 related mice model revealed the impact of this cytoplasmic fatty acid binding protein in the development of metabolic syndrome. In summary, investigating fat specific genes was amazingly powerful for analyses of the physiology of this tissue, as well as the etiology and complications of obesity.
Diabetes Res Clin Pract 2007 Sep
PMID:Role of adiponectin and adipocyte fatty acid binding protein in the metabolic syndrome. 1748 68


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