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)

Aquaporin 7 (AQP7), the gateway protein controlling glycerol release, has recently emerged as a modulator of adipocyte metabolism. AQP7 knockout mice develop obesity and hyperglycemia. The contribution of AQP7 to these abnormalities in humans is unknown. We examined whether common single nucleotide polymorphisms (SNPs) in the AQP7 gene modulate the risk of obesity and related abnormalities. Among several SNPs we identified, A-953G in the AQP7 promoter was associated with type 2 diabetes in 977 (530 female/447 male) Caucasians: odds ratio for XG (i.e., AG+GG) versus AA individuals was 1.36 (95% CI 1.01-1.84), P = 0.04. This finding was entirely due to the association among females (1.8 [1.2-2.6], P = 0.004), which was no longer significant when adjusted for BMI. In fact, BMI was higher in XG than in AA females (30.8 +/- 6.6 vs. 28.9 +/- 5.2, P = 0.002). This association was confirmed in independent case-control study (n = 299 female subjects) for morbid obesity (1.66 [1.01-2.74], P = 0.04). Luciferase and mobility shift assays showed that, compared with -953A, the -953G promoter had reduced transcriptional activity (P = 0.001) and impaired ability to bind CCAAT/enhancer binding protein (C/EBP)beta transcription factor (P = 0.01). Finally, AQP7 expression in adipose tissue decreased from AA to AG to GG individuals (P = 0.036). These data strongly suggest that AQP7 downregulation is pathogenic for obesity and/or type 2 diabetes.
Diabetes 2007 May
PMID:A functional variant of the adipocyte glycerol channel aquaporin 7 gene is associated with obesity and related metabolic abnormalities. 1735 Nov 48

Obesity and secondary development of type 2 diabetes (T2D) are major health care problems throughout the developed world. Accumulating evidence suggest that glycerol metabolism contributes to the pathophysiology of obesity and T2D. Glycerol is a small molecule that serves as an important intermediate between carbohydrate and lipid metabolism. It is stored primarily in adipose tissue as the backbone of triglyceride (TG) and during states of metabolic stress, such as fasting and diabetes, it is released for metabolism in other tissues. In the liver, glycerol serves as a gluconeogenic precursor and it is used for the esterification of free fatty acid into TGs. Aquaporin 7 (AQP7) in adipose tissue and AQP9 in the liver are transmembrane proteins that belong to the subset of AQPs called aquaglyceroporins. AQP7 facilitates the efflux of glycerol from adipose tissue and AQP7 deficiency has been linked to TG accumulation in adipose tissue and adult onset obesity. On the other hand, AQP9 expressed in liver facilitates the hepatic uptake of glycerol and thereby the availability of glycerol for de novo synthesis of glucose and TG that both are involved in the pathophysiology of diabetes. The aim of this review was to summarize the current knowledge on the role of the two glycerol channels in controlling glycerol metabolism in adipose tissue and liver.
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PMID:Metabolic impact of the glycerol channels AQP7 and AQP9 in adipose tissue and liver. 2446 99

Background Aquaporin 7 (AQP7), a water/glycerol transporting protein, regulates adipocyte glycerol efflux and influences lipid and glucose homeostasis. Altered AQP7 expression in adults leads to impaired glycerol dynamics, adipocyte hypertrophy and it predisposes them to obesity and diabetes. To assess its possible involvement in childhood obesity, this study investigated the expression of adipocyte AQP7 in cultured adipocytes of children. Methods Primary in vitro differentiated adipocyte cultures were developed from surgical biopsies of subcutaneous abdominal adipose tissue from 61 (46 prepubertal, 15 pubertal) lean children (body mass index [BMI] <85%) and 41 (22 prepubertal, 19 pubertal) children with obesity (BMI >95%). AQP7 expression was studied by reverse transcription polymerase chain reaction and Western immunoblotting and insulin by enzyme-linked immunosorbent assay. Results AQP7 messenger RNA (mRNA) was increased in the younger obese prepubertal (YOP) children but decreased in the obese adolescents (OA) (p=0.014) who also had increased insulin and homeostatic model assessment - insulin resistance (HOMA-IR). Lean pubertal (LP) children and YOP had increased 41 kDa AQP7 protein expression (p=0.001 and p=0.005, respectively). The OA who expressed 34 kDa AQP7 had lower triglyceride (TG) levels than those who did not express it (p=0.013). In the lean children, TG were negatively correlated with 34 kDa AQP7 (p=0.033). Conclusions The lower AQP7 mRNA expression in the OA may reflect a predisposition to adipocyte hypertrophy and metabolic dysfunction, as in the adults, whereas the YOP may be protected from this. The increased 41 kDa AQP7 protein expression in the LP may reflect the increased energy requirements of puberty for glycerol while in the YOP it may also be protective against the development of adipocyte hypertrophy.
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PMID:Adipocyte aquaporin 7 (AQP7) expression in lean children and children with obesity. Possible involvement in molecular mechanisms of childhood obesity. 3022 8