scholarly journals Synaptosomal Protein of 25 kDa (Snap25) Polymorphisms Associated with Glycemic Parameters in Type 2 Diabetes Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Nasser M. Al-Daghri ◽  
Andrea S. Costa ◽  
Majed S. Alokail ◽  
Milena Zanzottera ◽  
Amal M. Alenad ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Genomic Dna ◽  
Fasting Glucose ◽  
Glucose Levels ◽  
Intron 1 ◽  
Hba1c Levels

A possible role ofSnap25polymorphisms in type 2 diabetes mellitus (T2DM) was evaluated by analyzing three SNPs within intron 1 in a region known to affect the gene expression in vitro. Genomic DNA from 1019 Saudi individuals (489 confirmed T2DM and 530 controls) was genotyped for SNPs rs363039, rs363043, and rs363050 inSnap25using the TaqMan Genotyping Assay. Significantly higher levels of fasting glucose and HbA1c were detected in T2DM patients carrying the rs363050 (AG/GG) genotypes compared to the (AA) genotype (f=4.41,df=1, andp=0.03andf=5.31,df=1, andp=0.03, resp.). In these same patients, insulin levels were significantly decreased compared to the (AA) individuals (f=7.29,df=1, andp=0.009). Significant associations were detected between rs363050 (AG/GG) genotypes and increasing fasting glucose levels (p=0.01and OR: 1.05), HbA1c levels (OR: 5.06 andp=0.02), and lower insulinemia (p=0.03and OR: 0.95) in T2DM patients. The minorSnap25rs363050 (G) allele, which results in a reduced expression ofSnap25, is associated with altered glycemic parameters in T2DM possibly because of reduced functionality in the exocytotic machinery leading to suboptimal release of insulin.

scholarly journals Teucrium polium: Potential Drug Source for Type 2 Diabetes Mellitus

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 128
Author(s):  
Yaser Albadr ◽  
Andrew Crowe ◽  
Rima Caccetta
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Secretion ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glucose Levels ◽  
Teucrium Polium

The prevalence of type 2 diabetes mellitus is rising globally and this disease is proposed to be the next pandemic after COVID-19. Although the cause of type 2 diabetes mellitus is unknown, it is believed to involve a complex array of genetic defects that affect metabolic pathways which eventually lead to hyperglycaemia. This hyperglycaemia arises from an inability of the insulin-sensitive cells to sufficiently respond to the secreted insulin, which eventually results in the inadequate secretion of insulin from pancreatic β-cells. Several treatments, utilising a variety of mechanisms, are available for type 2 diabetes mellitus. However, more medications are needed to assist with the optimal management of the different stages of the disease in patients of varying ages with the diverse combinations of other medications co-administered. Throughout modern history, some lead constituents from ancient medicinal plants have been investigated extensively and helped in developing synthetic antidiabetic drugs, such as metformin. Teucrium polium L. (Tp) is a herb that has a folk reputation for its antidiabetic potential. Previous studies indicate that Tp extracts significantly decrease blood glucose levels r and induce insulin secretion from pancreatic β-cells in vitro. Nonetheless, the constituent/s responsible for this action have not yet been elucidated. The effects appear to be, at least in part, attributable to the presence of selected flavonoids (apigenin, quercetin, and rutin). This review aims to examine the reported glucose-lowering effect of the herb, with a keen focus on insulin secretion, specifically related to type 2 diabetes mellitus. An analysis of the contribution of the key constituent flavonoids of Tp extracts will also be discussed.

scholarly journals Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Denise E. Lackey ◽  
Felipe C. G. Reis ◽  
Roi Isaac ◽  
Rizaldy C. Zapata ◽  
Dalila El Ouarrat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Target Genes ◽  
Obese Mice ◽  
Tissue Macrophage

Abstract Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

scholarly journals Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

2019 ◽  
Vol 20 (6) ◽  
pp. 1517 ◽  
Author(s):  
Kai Wang ◽  
Yu Su ◽  
Yuting Liang ◽  
Yanhui Song ◽  
Liping Wang
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Enzymatic Activity ◽  
Glucose Levels ◽  
Blood Glucose Levels

Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction which can be induced by oxidative stress. Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6) is a microperoxidase mimetic that can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we demonstrated an increased stability of linear peptides upon their covalent attachment to porphyrins. In this study, we assessed the utility of DhHP-6 as an oral anti-diabetic drug in vitro and in vivo. DhHP-6 showed high resistance to proteolytic degradation in vitro and in vivo. The degraded DhHP-6 product in gastrointestinal (GI) fluid retained the enzymatic activity of DhHP-6, but displayed a higher permeability coefficient. DhHP-6 protected against the cell damage induced by H2O2 and promoted insulin secretion in INS-1 cells. In the T2DM model, DhHP-6 reduced blood glucose levels and facilitated the recovery of blood lipid disorders. DhHP-6 also mitigated both insulin resistance and glucose tolerance. Most importantly, DhHP-6 promoted the recovery of damaged pancreas islets. These findings suggest that DhHP-6 in physiological environments has high stability against enzymatic degradation and maintains enzymatic activity. As DhHP-6 lowered the fasting blood glucose levels of T2DM mice, it thus represents a promising candidate for oral administration and clinical therapy.

scholarly journals The Wnt signaling pathway effector TCF7L2 is upregulated by insulin and represses hepatic gluconeogenesis

2012 ◽  
Vol 303 (9) ◽  
pp. E1166-E1176 ◽  
Author(s):  
Wilfred Ip ◽  
Weijuan Shao ◽  
Yu-ting Alex Chiang ◽  
Tianru Jin
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Transcription Factor ◽  
Wnt Signaling ◽  
Wnt Signaling Pathway ◽  
Glucose Production ◽  
Hepatic Gluconeogenesis

Certain single nucleotide polymorphisms (SNPs) in transcription factor 7-like 2 (TCF7L2) are strongly associated with the risk of type 2 diabetes. TCF7L2 and β-catenin (β-cat) form the bipartite transcription factor cat/TCF in stimulating Wnt target gene expression. cat/TCF may also mediate the effect of other signaling cascades, including that of cAMP and insulin in cell-type specific manners. As carriers of TCF7L2 type 2 diabetes risk SNPs demonstrated increased hepatic glucose production, we aimed to determine whether TCF7L2 expression is regulated by nutrient availability and whether TCF7L2 and Wnt regulate hepatic gluconeogenesis. We examined hepatic Wnt activity in the TOPGAL transgenic mouse, assessed hepatic TCF7L2 expression in mice upon feeding, determined the effect of insulin on TCF7L2 expression and β-cat Ser675 phosphorylation, and investigated the effect of Wnt activation and TCF7L2 knockdown on gluconeogenic gene expression and glucose production in hepatocytes. Wnt activity was observed in pericentral hepatocytes in the TOPGAL mouse, whereas TCF7L2 expression was detected in human and mouse hepatocytes. Insulin and feeding stimulated hepatic TCF7L2 expression in vitro and in vivo, respectively. In addition, insulin activated β-cat Ser675 phosphorylation. Wnt activation by intraperitoneal lithium injection repressed hepatic gluconeogenic gene expression in vivo, whereas lithium or Wnt-3a reduced gluconeogenic gene expression and glucose production in hepatic cells in vitro. Small interfering RNA-mediated TCF7L2 knockdown increased glucose production and gluconeogenic gene expression in cultured hepatocytes. These observations suggest that Wnt signaling and TCF7L2 are negative regulators of hepatic gluconeogenesis, and TCF7L2 is among the downstream effectors of insulin in hepatocytes.

scholarly journals Genetic basis underlying connection between hyperglycemia and dyslipidemia in Apoe-deficient mice

2015 ◽  
Author(s):  
Qian Wang ◽  
Andrew Grainger ◽  
Ani Manichaikul ◽  
Emily Farber ◽  
Suna Onengut-Gumuscu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Fasting Glucose ◽  
Hdl Cholesterol ◽  
Western Diet ◽  
Chromosome 9 ◽  
Lipid Levels ◽  
Glucose Levels ◽  
Cholesterol Levels

Individuals with dyslipidemia often develop type 2 diabetes, and diabetic patients often have dyslipidemia. It remains to be determined whether there are genetic connections between the 2 disorders. A female F2 cohort, generated from BALB/cJ (BALB) and SM/J (SM) Apoe-deficient (Apoe−/−) strains, was fed a Western diet for 12 weeks. Fasting plasma glucose and lipid levels were measured before and after Western diet feeding. 144 genetic markers across the entire genome were used for analysis. One significant QTL on chromosome 9, named Bglu17 [26.4 cM, logarithm of odds ratio (LOD): 5.4], and 3 suggestive QTLs were identified for fasting glucose levels. The suggestive QTL near the proximal end of chromosome 9 (2.4 cM, LOD: 3.12) was detected when mice were fed chow or Western diet and named Bglu16. Bglu17 coincided with a significant QTL for HDL and a suggestive QTL for non-HDL cholesterol levels. Plasma glucose levels were inversely correlated with HDL but positively correlated with non-HDL cholesterol levels in F2 mice fed either diet. A significant correlation between fasting glucose and triglyceride levels was observed on the Western but not chow diet. Haplotype analysis revealed that ???lipid genes??? Sik3 and Apoc3 were probable candidates for Bglu17. We have identified multiple QTLs for fasting glucose and lipid levels. The colocalization of QTLs for both phenotypes and the sharing of potential causal genes suggest that dyslipidemia and type 2 diabetes are genetically connected.

scholarly journals Glucocorticoid signaling in pancreatic islets modulates gene regulatory programs and genetic risk of type 2 diabetes

2020 ◽  
Author(s):  
Anthony Aylward ◽  
Mei-Lin Okino ◽  
Paola Benaglio ◽  
Joshua Chiou ◽  
Elisha Beebe ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chromatin Accessibility ◽  
Enhancer Activity ◽  
Inflammatory Stress ◽  
Glucose Levels ◽  
Risk Variants ◽  
Glucocorticoid Signaling ◽  
Gene Regulatory

AbstractGlucocorticoids are key regulators of glucose homeostasis and pancreatic islet function, but the gene regulatory programs driving responses to glucocorticoid signaling in islets and the contribution of these programs to diabetes risk are unknown. In this study we used ATAC-seq and RNA-seq to map chromatin accessibility and gene expression from eight primary human islet samples cultured in vitro with the glucocorticoid dexamethasone. We identified 2,838 accessible chromatin sites and 1,114 genes with significant changes in activity in response to glucocorticoids. Chromatin sites up-regulated in glucocorticoid signaling were prominently enriched for glucocorticoid receptor binding sites and up-regulated genes were enriched for ion transport and lipid metabolism, whereas down-regulated chromatin sites and genes were enriched for inflammatory, stress response and proliferative processes. Genetic variants associated with glucose levels and T2D risk were enriched in glucocorticoid-responsive chromatin sites, including fine-mapped risk variants at 54 known signals. Among fine-mapped variants in glucocorticoid-responsive chromatin, a likely casual variant at the 2p21 locus had glucocorticoid-dependent allelic effects on beta cell enhancer activity and affected SIX2 and SIX3 expression. Our results provide a comprehensive map of islet regulatory programs in response to glucocorticoids through which we uncover a role for islet glucocorticoid signaling in mediating risk of type 2 diabetes.

What are the determinants of a concerned vision of the future when living with type 2 diabetes? Results from the E3N-AfterDiab study

2018 ◽  
Vol 15 (3) ◽  
pp. 236-241
Author(s):  
Guy Fagherazzi ◽  
Clélia Chambraud ◽  
Courtney Dow ◽  
Francesca Romana Mancini ◽  
Aurélie Affret ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Regression Models ◽  
Diabetes Management ◽  
Negative Experience ◽  
Glucose Lowering ◽  
Logistic Regression Models ◽  
Glucose Levels ◽  
The Future ◽  
Hba1c Levels

Objectives Identification of characteristics associated with a negative experience with type 2 diabetes may help to develop novel intervention to improve the outlook of people with the disease. Our aim was to identify determinants of a self-reported concerned vision about the future when living with type 2 diabetes. Methods In 2630 women with type 2 diabetes from the E3N-AfterDiab study, we used multivariable logistic regression models to derive odds-ratios and 95% confidence intervals. Results Women with elevated HbA1c levels (OR = 2.42 (1.67–3.49) for ≥7.2% when compared to <6.2%), or treated with injected glucose lowering treatments (OR = 1.37 [1.05–1.81]) had a higher risk of a concerned vision of the future. Age and obesity were associated with a decreased risk. Hypertension, duration of diabetes, smoking, fasting glucose levels, and years of education were not associated with a concerned vision of the future. Discussion Our findings highlight the importance of both glycemic control and the type of treatment on the perception of the future when living with type 2 diabetes. Subgroups of patients based on these characteristics may receive a specific attention from healthcare professionals to address potential concerns related with diabetes management or the fear of complications.

scholarly journals DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA1c levels: a systematic review and replication in a case–control sample of the Lifelines study

Diabetologia ◽  
2017 ◽  
Vol 61 (2) ◽  
pp. 354-368 ◽  
Author(s):  
Eliza Walaszczyk ◽  
Mirjam Luijten ◽  
Annemieke M. W. Spijkerman ◽  
Marc J. Bonder ◽  
Helen L. Lutgers ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Fasting Glucose ◽  
Control Sample ◽  
Case Control ◽  
Hba1c Levels
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