scholarly journals Comparison of gene expression in cynomolgus monkeys with preclinical type II diabetes induced by different high energy diets

2019 ◽  
Vol 2 (1) ◽  
pp. 44-50
Author(s):  
Li‐Sha Jin ◽  
Jun‐Hua Rao ◽  
Li‐Biao Zhang ◽  
Fang Ji ◽  
Yan‐Chun Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type Ii Diabetes ◽  
High Energy ◽  
Type Ii ◽  
Cynomolgus Monkeys

scholarly journals Type II diabetes may affect stem cell niche resulting in down regulation of glucose transporters and insulin receptors in cells

2018 ◽  
Author(s):  
Wenfa Ng
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Glucose Uptake ◽  
Type Ii Diabetes ◽  
Blood Glucose Concentration ◽  
Insulin Receptors ◽  
High Energy ◽  
The Body ◽  
Type Ii ◽  
High Blood Glucose

Characterized by high blood glucose concentration, resistance of cells to glucose uptake and reduced insulin sensitivity, Type II diabetes is a major health problem afflicting both developing and developed countries in increasing extent as populations around the world increasing adopt high energy diets. Given that, in Type II diabetes, successive generations of various cell types in the body ranging from muscles, tissues, blood, and organs are resistant to glucose uptake and exhibited reduced sensitivity to insulin, the underlying aetiology of Type II diabetes might involve the altered gene expression of stem cells in stem cell niches that adapted to a high glucose diet through an evolutionary conserved mechanism that aimed at homeostasis. Specifically, faced with a high energy and high sugar diet, stem cells in stem cell niches around the body possibly activated an evolutionary conserved mechanism aimed at reducing glucose uptake by cells for reducing weight gain by the body. Thus, successive generations of cells generated from the stem cell niche would exhibit an epigenetically controlled programme of gene expression that exhibited down regulation of genes for glucose transporters and insulin receptors. Such cells would display a phenotype of reduced glucose uptake together with reduced sensitivity to insulin; thereby, resulting in a high blood glucose concentration characteristic of Type II diabetes. The above hypothesis helped explain why high sugar intake by the body could result in impaired sensitivity to insulin and reduced glucose uptake by cells, and more importantly, the widespread nature in which many cell types (principally muscle cells) are affected by a possible epigenetically controlled gene expression programme which hitherto appeared clinically irreversible. Specifically, the most important clinical question for diabetes treatment and care remains the reasons underlying the clinically observed irreversible nature of the disease that progressively, with age and poor glucose control, worsens with complications to many organs of the body such as the eyes, kidneys, cardiovascular system and brain (stroke). Interested readers are invited to expand on the ideas presented in this abstract preprint.

scholarly journals Type II diabetes may affect stem cell niche resulting in down regulation of glucose transporters and insulin receptors in cells

2018 ◽  
Author(s):  
Wenfa Ng
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Glucose Uptake ◽  
Type Ii Diabetes ◽  
Blood Glucose Concentration ◽  
Insulin Receptors ◽  
High Energy ◽  
The Body ◽  
Type Ii ◽  
High Blood Glucose

Characterized by high blood glucose concentration, resistance of cells to glucose uptake and reduced insulin sensitivity, Type II diabetes is a major health problem afflicting both developing and developed countries in increasing extent as populations around the world increasing adopt high energy diets. Given that, in Type II diabetes, successive generations of various cell types in the body ranging from muscles, tissues, blood, and organs are resistant to glucose uptake and exhibited reduced sensitivity to insulin, the underlying aetiology of Type II diabetes might involve the altered gene expression of stem cells in stem cell niches that adapted to a high glucose diet through an evolutionary conserved mechanism that aimed at homeostasis. Specifically, faced with a high energy and high sugar diet, stem cells in stem cell niches around the body possibly activated an evolutionary conserved mechanism aimed at reducing glucose uptake by cells for reducing weight gain by the body. Thus, successive generations of cells generated from the stem cell niche would exhibit an epigenetically controlled programme of gene expression that exhibited down regulation of genes for glucose transporters and insulin receptors. Such cells would display a phenotype of reduced glucose uptake together with reduced sensitivity to insulin; thereby, resulting in a high blood glucose concentration characteristic of Type II diabetes. The above hypothesis helped explain why high sugar intake by the body could result in impaired sensitivity to insulin and reduced glucose uptake by cells, and more importantly, the widespread nature in which many cell types (principally muscle cells) are affected by a possible epigenetically controlled gene expression programme which hitherto appeared clinically irreversible. Specifically, the most important clinical question for diabetes treatment and care remains the reasons underlying the clinically observed irreversible nature of the disease that progressively, with age and poor glucose control, worsens with complications to many organs of the body such as the eyes, kidneys, cardiovascular system and brain (stroke). Interested readers are invited to expand on the ideas presented in this abstract preprint.

Mest/Peg1 imprinted gene enlarges adipocytes and is a marker of adipocyte size

2005 ◽  
Vol 288 (1) ◽  
pp. E117-E124 ◽  
Author(s):  
Mayumi Takahashi ◽  
Yasutomi Kamei ◽  
Osamu Ezaki
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Transgenic Mice ◽  
Type Ii Diabetes ◽  
Binding Protein ◽  
Ectopic Expression ◽  
Peroxisome Proliferator ◽  
Type Ii ◽  
Fatty Acid Binding ◽  
Enhanced Expression

Obesity is a common and serious metabolic disorder in the developed world that is occasionally accompanied by type II diabetes, atherosclerosis, hypertension, and hyperlipidemia. We have found that mesoderm-specific transcript (Mest)/paternally expressed gene 1 (Peg1) gene expression was markedly enhanced in white adipose tissue of mice with diet-induced and genetically caused obesity/diabetes but not with streptozotocin-induced diabetes, which does not cause obesity. Administration of pioglitazone, a drug for type II diabetes and activator of peroxisome proliferator-activated receptor (PPAR)γ, in obese db/ db mice reduced the enhanced expression of Mest mRNA in adipose tissue, concomitant with an increase in body weight and a decrease in the size of adipose cells. Ectopic expression of Mest in 3T3-L1 cells caused increased gene expression of adipose markers such as PPARγ, CCAAT/enhancer binding protein (C/EBP)α, and adipocyte fatty acid binding protein (aP)2. In transgenic mice overexpressing Mest in adipose tissue, enhanced expression of the adipose genes was observed. Moreover, adipocytes were markedly enlarged in the transgenic mice. Thus Mest appears to enlarge adipocytes and could be a novel marker of the size of adipocytes.

scholarly journals Genetic Determinants of Obesity Heterogeneity in Type II Diabetes

2020 ◽  
Author(s):  
Somayeh Alsadat Hosseini Khorami ◽  
Mohd Sokhini Abd Mutalib ◽  
Mohammad Feili Shiraz ◽  
Joseph Anthony Abdullah ◽  
Zulida Rejali ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Molecular Mechanism ◽  
Type Ii Diabetes ◽  
Insulin Signalling ◽  
Diabetic Group ◽  
Akt Pathway ◽  
Type Ii ◽  
Fasting State ◽  
Significant Difference

Abstract Background: Although obesity is considered as the main cause of Type II diabetes (T2DM), non-obese individuals may still develop T2DM and obese individuals may not. Method: The mRNA expression of insulin signalling components (PI3K/AKT axis) from 100 non-obese and obese participants with insulin sensitivity and insulin resistance states were compared in this study toward the understanding of obesity heterogeneity molecular mechanism. Result: In present study, there was no statistically significant difference in gene expression levels of IRS1 and PTEN between groups, whereas PI3K, AKT2 and GLUT4 genes were expressed at a lower level in obese diabetic group compared to other groups. PDK1 gene was expressed at a higher level in non-obese diabetic group compared to obese diabetic and non-obese non-diabetics groups. No statistically significant difference was identified in gene expression pattern of PI3K/AKT pathway between obese non-diabetics and non-obese non-diabetics. Conclusion: The components of PI3K/AKT pathway which is related to the fasting state, showed reduced expression in obese diabetic group due to the chronic over-nutrition which may induced insensitivity and reduced gene expression. The pathogenesis of insulin resistance in the absence of obesity in non-obese diabetic group could be due to disturbance in another pathway related to the non-fasting state like gluconeogenesis. Therefore, the molecular mechanism of insulin signalling in non-obese diabetic individuals is different from obese diabetics which more investigations are required to study insulin signalling pathways in greater depth, in order to assess nutritional factors contribute to insulin resistance in obese diabetic and non-obese diabetic individuals.

scholarly journals Sex differences in disease genetics

2016 ◽  
Author(s):  
William P. Gilks
Keyword(s):  
Gene Expression ◽  
Type Ii Diabetes ◽  
Disease Risk ◽  
Genetic Effect ◽  
Genetic Effects ◽  
List Type ◽  
Type Ii ◽  
Genome Wide ◽  
Inflammatory Bowel ◽  
Males And Females

AbstractThere is long-standing evidence for gene-by-sex interactions in disease risk, which can now be tested in genome-wide association studies with participant numbers in the hundreds of thousands. Contemporary methods start with a separate test for each sex, but simulations suggest a more powerful approach should be to use sex as an interaction term in a single test. The traits currently with the most compelling evidence for sex-dependent genetic effects are for adiposity (predictive of cardiac disease), type II diabetes, asthma and inflammatory bowel disease. Sexually dimorphic gene expression varies dynamically, by age, tissue type, and chromosome, so sex dependent genetic effects are expected for a wide range of diseases.Key conceptsCompelling findings of sex-dependent genetic effects on disease have been made in adiposity-related anthropometric traits, type II diabetes, and inflammatory bowel disease. Other disorders remain to be more fully investigated, regardless of what sexual differences they exhibit in prevalence and presentation.Current evidence indicates that sex difference in gene expression is not required for a SNP to have a sex-dependent effect. However, sex differences in gene expression vary dynamically, by organ and age, so generalisations may be inaccurate without comprehensive data.Sex-dependent risk alleles are predicted to be of greater effect size than conventional ones, because natural selection acts only against the sex which has the disease. There is evidence for this from a high-powered GWAS of adiposity-related traits.Many of the large GWAS meta-analyses look for sex-dependent genetic effects by testing male and female groups separately. However, this may be under-powered compared to a whole-sample, gene-by-sex interaction test.GlossaryGenome-wide association study (GWAS). Method for identifying molecular genetic variation that controls heritable traits, in a population sample. Involves assessing the correlation between allele frequencies and phenotype value, at millions of markers of common genetic variation across the genome.Sexual dimorphism. A difference between males and females in a population for the value of a particular trait. May include anything from anatomical measurements to expression level of a gene.Sex-dependent genetic effect. A disease risk allele is termed sex-specific when it increases risk in one sex only but has no effect on the disease in the other sex. The term sex-biased is used for an allele causes a significant increase in risk of disease in both sexes, but for which the magnitude of the risk increase is significantly different between males and females. There are also reports where an allele that increases risk of a disease in one sex reduces risk of the same disease in the other sex but none have been replicated, and there is no biochemical reason why this could be true. It effectively constitutes a sexually antagonistic effect, but should be distinguished from intra-locus sexual conflict which explicitly requires than an allele have opposing effects on the evolutionary fitness of males and females (Bonduriansky and Chenoweth 2009). All of the above relationships constitute a form of sex-dependent genetic effect.

scholarly journals Aberration of the modulatory functions of intronic microRNA hsa-miR-933 on its host gene ATF2 results in type II diabetes mellitus and neurodegenerative disease development

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Abul Bashar Mir Md. Khademul Islam ◽  
Eusra Mohammad ◽  
Md. Abdullah-Al-Kamran Khan
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Host Gene ◽  
Functional Enrichment ◽  
Type Ii ◽  
Intronic Mirnas ◽  
The Common ◽  
Host Genes

Abstract Background MicroRNAs are ~ 22-nucleotide-long biological modifiers that act as the post-transcriptional modulator of gene expression. Some of them are identified to be embedded within the introns of protein-coding genes, these miRNAs are called the intronic miRNAs. Previous findings state that these intronic miRNAs are co-expressed with their host genes. This co-expression is necessary to maintain the robustness of the biological system. Till to date, only a few experiments are performed discretely to elucidate the functional relationship between few co-expressed intronic miRNAs and their associated host genes. Results In this study, we have interpreted the underlying modulatory mechanisms of intronic miRNA hsa-miR-933 on its target host gene ATF2 and found that aberration can lead to several disease conditions. A protein-protein interaction network-based approach was adopted, and functional enrichment analysis was performed to elucidate the significantly over-represented biological functions and pathways of the common targets. Our approach delineated that hsa-miR-933 might control the hyperglycemic condition and hyperinsulinism by regulating ATF2 target genes MAP4K4, PRKCE, PEA15, BDNF, PRKACB, and GNAS which can otherwise lead to the development of type II diabetes mellitus. Moreover, we showed that hsa-miR-933 can regulate a target of ATF2, brain-derived neurotrophic factor (BDNF), to modulate the optimal expression of ATF2 in neuron cells to render neuroprotection for the inhibition of neurodegenerative diseases. Conclusions Our in silico model provides interesting resources for experimentations in a model organism or cell line for further validation. These findings may extend the common perception of gene expression analysis with new regulatory functionality.

scholarly journals Downregulation of Type II Diabetes Mellitus and Maturity Onset Diabetes of Young Pathways in Human Pancreatic Islets from Hyperglycemic Donors

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jalal Taneera ◽  
Petter Storm ◽  
Leif Groop
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Pancreatic Islets ◽  
Type Ii Diabetes ◽  
Enrichment Analysis ◽  
Type Ii Diabetes Mellitus ◽  
Type Ii ◽  
Maturity Onset Diabetes ◽  
Human Pancreatic Islets ◽  
Onset Diabetes

Although several molecular pathways have been linked to type 2 diabetes (T2D) pathogenesis, it is uncertain which pathway has the most implication on the disease. Changes in the expression of an entire pathway might be more important for disease pathogenesis than changes in the expression of individual genes. To identify the molecular alterations in T2D, DNA microarrays of human pancreatic islets from donors with hyperglycemian=20and normoglycemian=58were subjected to Gene Set Enrichment Analysis (GSEA). About 178 KEGG pathways were investigated for gene expression changes between hyperglycemic donors compared to normoglycemic. Pathway enrichment analysis showed that type II diabetes mellitus (T2DM) and maturity onset diabetes of the young (MODY) pathways are downregulated in hyperglycemic donors, while proteasome and spliceosome pathways are upregulated. The mean centroid of gene expression of T2DM and MODY pathways was shown to be associated positively with insulin secretion and negatively with HbA1c level. To conclude, downregulation of T2DM and MODY pathways is involved in islet function and might be involved in T2D. Also, the study demonstrates that gene expression profiles from pancreatic islets can reveal some of the biological processes related to regulation of glucose hemostats and diabetes pathogenesis.

scholarly journals Troglitazone Effects on Gene Expression in Human Skeletal Muscle of Type II Diabetes Involve Up-Regulation of Peroxisome Proliferator-Activated Receptor-γ1

1998 ◽  
Vol 83 (8) ◽  
pp. 2830-2835 ◽  
Author(s):  
Kyong Soo Park ◽  
Theodore P. Ciaraldi ◽  
Kristin Lindgren ◽  
Leslie Abrams-Carter ◽  
Sunder Mudaliar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Type Ii Diabetes ◽  
Insulin Action ◽  
Peroxisome Proliferator ◽  
Type Ii ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nondiabetic Control ◽  
Muscle Cultures ◽  
Stimulation Of

abstract Troglitazone, besides improving insulin action in insulin-resistant subjects, is also a specific ligand for the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ). To determine whether troglitazone might enhance insulin action by stimulation of PPARγ gene expression in muscle, total PPARγ messenger RNA (mRNA), and protein were determined in skeletal muscle cultures from nondiabetic control and type II diabetic subjects before and after treatment of cultures with troglitazone (4 days ± troglitazone, 11.5μ m). Troglitazone treatment increased PPARγ mRNA levels up to 3-fold in muscle cultures from type II diabetics (277 ± 63 to 630 ± 100 × 103 copies/μg total RNA, P = 0.003) and in nondiabetic control subjects (200 ± 42 to 490 ± 81, P = 0.003). PPARγ protein levels in both diabetic (4.7 ± 1.6 to 13.6± 3.0 AU/10 μg protein, P < 0.02) and nondiabetic cells (7.4 ± 1.0 to 12.7 ± 1.8, P < 0.05) were also up-regulated by troglitazone treatment. Increased PPARγ was associated with stimulation of human adipocyte lipid binding protein (ALBP) and muscle fatty acid binding protein (mFABP) mRNA, without change in the mRNA for glycerol-3-phosphate dehydrogenase, PPARδ, myogenin, uncoupling protein-2, or sarcomeric α-actin protein. In summary, we showed that troglitazone markedly induces PPARγ, ALBP, and mFABP mRNA abundance in muscle cultures from both nondiabetic and type II diabetic subjects. Increased expression of PPARγ protein and other genes involved in glucose and lipid metabolism in skeletal muscle may account, in part, for the insulin sensitizing effects of troglitazone in type II diabetes.

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