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Hemang Parikh

Publications and source records attributed to Hemang Parikh.

5 recordsLinked to original sources
PubMed2006

Variation in the adiponutrin gene influences its expression and associates with obesity.

Adiponutrin is one of three recently identified adipocyte lipases. Surprisingly, these proteins also retain transacylase activity, a hitherto unknown pathway of triacylglycerol synthesis in the adipocytes. This may enable them to participate in both anabolic and catabolic processes. The adiponutrin gene (ADPN) is downregulated by fasting and upregulated by refeeding, suggesting a role in lipogenesis. Experiments in human adipocytes confirmed that the gene is upregulated in response to insulin in a glucose-dependent fashion. Obese subjects had increased levels of subcutaneous and visceral abdominal adipose tissue ADPN mRNA. Visceral ADPN mRNA expression was correlated to measures of insulin sensitivity (fasting insulin and homeostasis model assessment). We also studied genetic variation in ADPN and its relation to obesity, lipolysis, and mRNA expression. Two ADPN polymorphisms showed association with obesity. Carriers of the obesity-associated variants showed a lesser increase in the levels of adipose tissue ADPN mRNA and an increased basal lipolysis. Our results suggest that obese subjects that are insulin resistant and/or carriers of the obesity-associated ADPN alleles fail to upregulate the gene and that upregulation of adiponutrin may be an appropriate response to orchestrate energy excess.

Adult↗
PubMed2005

Overexpression of immediate early genes in active Graves' ophthalmopathy.

CONTEXT: In Graves' ophthalmopathy a major problem is an increase in the intraorbital adipose tissue volume. OBJECTIVE: The aim of this work was to define mechanisms of orbital adipogenesis. DESIGN: This was an open-label prospective study. SETTING: The study was conducted at the Clinic of Endocrinology, University Hospital. PARTICIPANTS: The study consisted of patients (n = 5) with severe ophthalmopathy with affection of the optic nerve and thyroid healthy controls (n = 5). INTERVENTIONS: We performed lateral decompression of orbital tissue in patients unresponsive to corticosteroids and restorative surgery of the upper eyelid in thyroid healthy controls. MAIN OUTCOME MEASURE: We made large-scale measurements of gene expression, with microarray technique based on determination of fluorescence intensities in cases and controls. RESULTS: A marker of adipose tissue, stearoyl-coenzyme A desaturase, was overexpressed in ophthalmopathy, and selection criteria were set to favor identification of genes known to be expressed in normal adipogenesis. The immediate early gene, cysteine-rich, angiogenic inducer, 61 (CYR61), was overexpressed in addition to 15 other immediate early genes (IEGs), and the expression of selected IEGs was confirmed with RT-PCR: CYR61, cyclooxygenase-2, dual-specificity phosphatase 1, B cell translocation gene 2, and early growth response 1. CYR61-responsive genes, known to participate in inflammation, IL-1beta, matrix metalloproteinase-3, and vascular endothelial growth factor were also overexpressed. Patients showed greater expression of CYR61 in the active than the chronic phase of ophthalmopathy, indicating that CYR61 is a marker of disease activity. Cyclooxygenase-2, the target gene of IL-1beta, was also overexpressed, although all patients had been treated with corticosteroids. CONCLUSION: Adipocyte-related IEGs are overexpressed in active ophthalmopathy, and CYR61 may have a role in both orbital inflammation and adipogenesis and serve as a marker of disease activity.

Adipose Tissue↗
PubMed2005

Haplotype construction of the FRDA gene and evaluation of its role in type II diabetes.

A GAA-repeat in the X25 gene is causing Friedreich's ataxia (FRDA), a common neurodegenerative disease and >20% of FRDA patients develop type II diabetes (T2D). Linkage has previously been detected between T2D and chromosome 9p13-q21, the region that harbours the X25 gene, but association studies of this gene in T2D have been contradicting. Here, we examined whether genetic variation in the X25 gene is associated with risk for T2D. The GAA-repeat and 18 single nucleotide polymorphisms (SNPs) covering the X25 gene were genotyped in 220 trios in which the affected offspring had abnormal glucose tolerance. Any nominally significant findings were examined in an independent sample consisting of 523 individuals with T2D and 326 healthy controls. Previously reported results were analysed together with our data using a meta-analysis approach. There was no association between the GAA-repeat and T2D susceptibility in our study, which was supported by the meta-analysis including all previous publications. One SNP (rs2498429), 8.2 kb downstream of X25, was nominally associated with T2D in the trios (P=0.02) and showed a trend of association in the same direction in the case-controls (P=0.08; combined permuted P=0.01). Further analysis showed that the nine-marker haplotype containing the rare allele of rs2498429 was nominally associated with T2D in the trios (P<0.01) as well as in the case-controls (P=0.03). In conclusions, this study excludes a role of genetic variation within the X25 gene, but instead suggests that genetic variation downstream the X25 gene, may increase risk for T2D.

Adult↗
PubMed2005

Calpain 10 and type 2 diabetes: are we getting closer to an explanation?

PURPOSE OF REVIEW: A variation in the gene encoding the cysteine protease calpain 10 (CAPN10) was recently linked and associated with type 2 diabetes by positional cloning. This positional cloning was a follow-up investigation to the identification of a diabetes-linked region on human chromosome 2 identified by genome-wide scanning a few years earlier. In this paper we give a general background on the genetic studies performed on CAPN10 to date, and review the most recent studies on the functional role of calpain 10. RECENT FINDING: A haplotype or haplotype combination comprising three intronic single nucleotide polymorphisms (UCSNP-43, 19, and 63) were associated with a threefold increased risk of type 2 diabetes in the population in which linkage was first found. Another polymorphism, UCSNP-44, which is in linkage disequilibrium with a coding single-nucleotide polymorphism (Thr504Ala), has subsequently been associated with type 2 diabetes in extensive meta-analyses. Meanwhile, initial studies probing the possible role of calpain-10, completely unknown at the time, are now being pursued, both in isolated cells and humans. SUMMARY: The positional cloning of CAPN10 as a candidate gene for type 2 diabetes has been particularly fruitful. Not only has it identified an important and surprising piece of the puzzle underlying the development of diabetes, but it has also modelled and paved the way for investigations concerning complex genetic diseases other than type 2 diabetes.

Calpain↗