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  1. Insulin secreted from genetically engineered intestinal cells reduces blood glucose levels in diabetic mice
    Rasouli M, Allaudin ZN, Omar AR, Ahmad Z
    Curr Gene Ther, 2013 Aug;13(4):229-39.
    PMID: 23721205 DOI: 10.2174/15665232113139990002
    Poorly controlled diabetes mellitus can result in serious complications. Gene therapy is increasingly being considered as an alternative approach to treat diabetes, because of its ability to induce physiological insulin secretion and it allows patients to escape insulin injections. The properties of gut K and L-cells, including glucose sensitivity, the ability to process insulin and a regulated secretion pathway support their use as surrogate β-cells. Previous in vitro studies have provided sufficient evidence supporting the use of these cells for gene therapy studies. Therefore, we examined the ability of K and L-cells to produce insulin in diabetic mice. Chitosan nanoparticles were used to transfer the insulin gene into intestinal cells via oral administration. The efficiency of chitosan as a gene vehicle was investigated through the use of reporter gene. Insulin mRNA and protein expression levels were measured by RT-PCR and ELISA, respectively. Blood glucose testing revealed that this treatment reduced glucose levels in diabetic mice. The decrease in blood glucose level in the first week of treatment was greater in mice with K-cell specific insulin expression compared with mice with L-cell-specific insulin expression. These results indicate that inducing insulin secretion in K-cells conferred a quicker response to gene therapy.
    Matched MeSH terms: Blood Glucose/genetics
  2. Nutrigenomic effects of germinated brown rice and its bioactives on hepatic gluconeogenic genes in type 2 diabetic rats and HEPG2 cells
    Imam MU, Ismail M
    Mol Nutr Food Res, 2013 Mar;57(3):401-11.
    PMID: 23307605 DOI: 10.1002/mnfr.201200429
    SCOPE: Chronic sustained hyperglycemia underlies the symptomatology and complications of type 2 diabetes mellitus, and dietary components contribute to it. Germinated brown rice (GBR) improves glycemic control but the mechanisms involved are still the subject of debate. We now show one mechanism by which GBR lowers blood glucose.

    METHODS AND RESULTS: Effects of GBR, brown rice, and white rice (WR) on fasting plasma glucose and selected genes were studied in type 2 diabetic rats. GBR reduced plasma glucose and weight more than metformin, while WR worsened glycemia over 4 weeks of intervention. Through nutrigenomic suppression, GBR downregulated gluconeogenic genes (Fbp1 and Pck1) in a manner similar to, but more potently than, metformin, while WR upregulated the same genes. Bioactives (gamma-amino butyric acid, acylated steryl glycoside, oryzanol, and phenolics) were involved in GBR's downregulation of both genes. Plasma glucose, Fbp1 and Pck1 changes significantly affected the weight of rats (p = 0.0001).

    CONCLUSION: The fact that GBR downregulates gluconeogenic genes similar to metformin, but produces better glycemic control in type 2 diabetic rats, suggests other mechanisms are involved in GBR's antihyperglycemic properties. GBR as a staple could potentially provide enhanced glycemic control in type 2 diabetes mellitus better than metformin.

    Matched MeSH terms: Blood Glucose/genetics
  3. Genome-Wide Association for HbA1c in Malay Identified Deletion on SLC4A1 that Influences HbA1c Independent of Glycemia
    Chai JF, Kao SL, Wang C, Lim VJ, Khor IW, Dou J, et al.
    J Clin Endocrinol Metab, 2020 Dec 01;105(12).
    PMID: 32936915 DOI: 10.1210/clinem/dgaa658
    CONTEXT: Glycated hemoglobin A1c (HbA1c) level is used to screen and diagnose diabetes. Genetic determinants of HbA1c can vary across populations and many of the genetic variants influencing HbA1c level were specific to populations.

    OBJECTIVE: To discover genetic variants associated with HbA1c level in nondiabetic Malay individuals.

    DESIGN AND PARTICIPANTS: We conducted a genome-wide association study (GWAS) analysis for HbA1c using 2 Malay studies, the Singapore Malay Eye Study (SiMES, N = 1721 on GWAS array) and the Living Biobank study (N = 983 on GWAS array and whole-exome sequenced). We built a Malay-specific reference panel to impute ethnic-specific variants and validate the associations with HbA1c at ethnic-specific variants.

    RESULTS: Meta-analysis of the 1000 Genomes imputed array data identified 4 loci at genome-wide significance (P 

    Matched MeSH terms: Blood Glucose/genetics
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