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- Broadaway, K Alaine, et al.
(author)
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Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
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In: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
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Journal article (peer-reviewed)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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- Shukla, S., et al.
(author)
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Appraisal of groundwater chemistry, its suitability for crop productivity in Sonipat district and human health risk evaluation
- 2023
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In: Human and Ecological Risk Assessment. - : Informa UK Limited. - 1080-7039 .- 1549-7860. ; 29:2, s. 507-528
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Journal article (peer-reviewed)abstract
- The present study was taken with a primary objective to estimate the groundwater quality and its suitability toward sustainable crop productivity in an agriculturally dominant semi-urban area. Elevated levels of nitrate have severe health impacts and affect the human health. Hence, health risks associated with the consumption of nitrate contaminated water were estimated for adults and children in Sonipat district, Haryana. In general, the groundwater was found to be slightly alkaline and moderately hard. The anionic abundance was verified as F– < NO3– < HCO3– < SO42– < Cl–, whereas, the cationic abundance was verified as Ca2+ < Mg2+ < K+ < Na+. Concentration of nitrate varied from 1.34 mg/L to 565 mg/L, with an average value of 47.6 mg/L, and 46% of the groundwater samples had nitrate concentration of more than 45 mg/L. As per the results of Wilcox plot, only 34% of samples were suitable for crop productivity, whereas 23% of the samples fell in category-II of the permeability index. The non-carcinogenic health risk assessment further suggested that hazard quotient values for nitrate reached as high as 18.35 (children), and 13.57 (adult male), suggesting that health risk degree of children has greater health risk than adults in the study region. Overall results suggest an urgent need for intervention to adopt suitable health risk measures to reduce exposure toward nitrate contaminated drinking water. Moreover, agricultural practices must be improved to increase the crop productivity in the affected areas.
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- Antonson, P., et al.
(author)
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Identification of proteins highly expressed in uterine fluid from mice with hydrometra
- 2015
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 466:4, s. 650-655
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Journal article (peer-reviewed)abstract
- Estrogen receptor alpha (ER alpha) is an important regulator of the estrous cycle and mice with global ER alpha deletion, as well as some conditional knockout mouse lines, have an interruption in the estrous cycle. In this study we observed that conditional ERa knockout mice where the Cre gene is regulated by the rat insulin promoter (RIP), RIP-Cre/ER alpha(KO) mice, have a 3.7-fold increase in serum 17 beta-estradiol levels, blocked estrous cycle, and develop a fluid-filled uterus (hydrometra). Using a proteomics approach, we identified three proteins, lactoferrin, complement C3 and chitinase 3-like protein 1 (CHI3L1), as highly expressed proteins in hydrometra fluid. The mRNA levels of the corresponding genes were more than 50-fold higher in RIP-Cre/ER alpha(KO) uterus compared to controls. High expression of CHI3L1 in the uterine fluid was not reflected as elevated levels in the serum. The high expression of lactoferrin, complement C3 and CHI3L1 in the uterine fluid, in association with elevated estrogen levels, prompted us to address if the expression of these genes is related to reproduction. However, gonadotropin treatment of mice reduced the uterine expression of these genes in a model of in vitro fertilization. Our findings identify lactoferrin, complement C3 and CHI3L1 as highly expressed proteins in hydrometra fluid in association with chronically elevated serum estradiol levels. (C) 2015 Elsevier Inc. All rights reserved.
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