scholarly journals Roles of Nicotinamide N-Methyltransferase in Obesity and Type 2 Diabetes

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jie-Ru Liu ◽  
Zhao-Hui Deng ◽  
Xiao-Juan Zhu ◽  
Yu-Rong Zeng ◽  
Xiang-Xiang Guan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fasting Blood Glucose ◽  
Energy Utilization ◽  
Glucose Levels ◽  
Promising Therapeutic Target ◽  
Acting Mechanism ◽  
Preclinical Animal Models ◽  
Abnormal Lipid Metabolism

Type 2 diabetes (T2D) is thought to be a complication of metabolic syndrome caused by disorders of energy utilization and storage and characterized by insulin resistance or deficiency of insulin secretion. Though the mechanism linking obesity to the development of T2D is complex and unintelligible, it is known that abnormal lipid metabolism and adipose tissue accumulation possibly play important roles in this process. Recently, nicotinamide N-methyltransferase (NNMT) has been emerging as a new mechanism-of-action target in treating obesity and associated T2D. Evidence has shown that NNMT is associated with obesity and T2D. NNMT inhibition or NNMT knockdown significantly increases energy expenditure, reduces body weight and white adipose mass, improves insulin sensitivity, and normalizes glucose tolerance and fasting blood glucose levels. Additionally, trials of oligonucleotide therapeutics and experiments with some small-molecule NNMT inhibitors in vitro and in preclinical animal models have validated NNMT as a promising therapeutic target to prevent or treat obesity and associated T2D. However, the exact mechanisms underlying these phenomena are not yet fully understood and clinical trials targeting NNMT have not been reported until now. Therefore, more researches are necessary to reveal the acting mechanism of NNMT in obesity and T2D and to develop therapeutics targeting NNMT.

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 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 Nocturnal Glucose Metabolism after Bedtime Injection of Insulin Glargine or Neutral Protamine Hagedorn Insulin in Patients with Type 2 Diabetes

2008 ◽  
Vol 93 (10) ◽  
pp. 3839-3846 ◽  
Author(s):  
Thomas Linn ◽  
Britta Fischer ◽  
Nedim Soydan ◽  
Michael Eckhard ◽  
Julia Ehl ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Glargine ◽  
Fasting Blood Glucose ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Nph Insulin ◽  
Double Blind ◽  
Glucose Levels ◽  
Neutral Protamine Hagedorn

Aims/Hypothesis: Insulin glargine is a long-acting human insulin analog often administered at bedtime to patients with type 2 diabetes. It reduces fasting blood glucose levels more efficiently and with less nocturnal hypoglycemic events compared with human neutral protamine Hagedorn (NPH) insulin. Therefore, bedtime injections of insulin glargine and NPH insulin were compared overnight and in the morning. Methods: In 10 type 2 diabetic patients, euglycemic clamps were performed, including [6,6′]2H2 glucose, to study the rate of disappearance (Rd) and endogenous production (EGP) of glucose during the night. On separate days at bedtime (2200 h), patients received a sc injection of insulin glargine, NPH insulin, or saline in a randomized, double-blind fashion. Results: Similar doses of both insulins had different metabolic profiles. NPH insulin had a greater effect on both Rd and EGP in the night compared with insulin glargine. By contrast, in the morning, insulin glargine was more effective, increasing Rd by 5.8 μmol/kg−1·min−1 (95% confidence interval 4.7–6.9) and reducing EGP −5.7 (−5.0 to −6.4) compared with NPH insulin. Nearly 80% of the glucose lowering effect in the morning was due to insulin glargine’s reduction of EGP. Its injection was associated with one-third lower morning glucagon levels compared with NPH insulin (P = 0.021). Conclusion/Interpretation: Nocturnal variations of EGP and Rd explain the reduced incidence of hypoglycemia and lower fasting glucose levels reported for insulin glargine compared with human NPH insulin.

scholarly journals Factors Associated with Glycaemic Control among Diabetic Patients Managed at an Urban Hospital in Hanoi, Vietnam

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Luu Quang Thuy ◽  
Hoang Thi Phuong Nam ◽  
Tran Thi Ha An ◽  
Bui Van San ◽  
Tran Nguyen Ngoc ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycaemic Control ◽  
Associated Factors ◽  
Fasting Blood Glucose ◽  
Management Strategies ◽  
Diabetic Patients ◽  
Urban Hospital ◽  
Glucose Levels ◽  
Blood Glucose Levels

Type 2 diabetes (T2DM) epidemic is rising in Vietnam. Identifying associated factors with glycaemic control in patients with T2DM is vital to improve treatment outcomes. This study is aimed at examining the uncontrolled glycaemic level of patients with type 2 diabetes (T2DM) at an urban hospital in Hanoi, Vietnam, and determining associated factors. An observational longitudinal cohort survey was performed among T2DM patients. Glycaemic control was evaluated by using the HbA 1 c   level ≥ 6.5 % or fasting blood   glucose   level ≥ 7.5   g / mmol . Information about sociodemographic, clinical, and behavioral characteristics was collected. Multivariate mixed-effects logistic regression was employed to identify associated factors with control glycaemic level conditions. Among 189 T2DM patients, 70.4% had an uncontrolled glycaemic level. A higher number of comorbidities were associated with a lower likelihood of having uncontrolled glycaemic levels ( OR = 0.71 , p < 0.001 , 95 % CI = 0.52 − 0.98 ). Meanwhile, a higher body mass index ( OR = 1.15 , p < 0.05 , 95 % CI = 1.02 − 1.29 ), higher initial HbA1C ( OR = 3.75 , p < 0.01 , 95 % CI = 2.59 − 5.44 ), and higher initial fasting blood glucose levels ( OR = 1.57 , p < 0.01 , 95 % CI = 1.29 − 1.90 ) were positively associated with a higher risk of uncontrolled glycaemic levels. This study reveals that poor glycaemic control was common among T2DM patients in the urban hospital in Vietnam. Findings underlined the need for appropriate management strategies to control glycaemic levels and weight in this population.

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.

scholarly journals Cadmium Exposure Decreases Fasting Blood Glucose Levels and Exacerbates Type-2 Diabetes in a Mouse Model

2021 ◽  
Author(s):  
Mengyang Li ◽  
Shuai Wang ◽  
Xiuxiu Liu ◽  
Zhijie Sheng ◽  
Bingyan Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Diabetic Group ◽  
Diabetic Mice ◽  
Hepatic Enzymes ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Cd Exposure

Abstract Purpose Although the effects of cadmium (Cd) on the development of diabetes have been extensively investigated, the relationship between Cd exposure and the severity of established diabetes is unclear. Herein, we investigate the effects of long-term exposure to Cd in a streptozotocin-induced mouse model of type 2 diabetes and the underlying mechanism. Methods C57BL/6 Mice were divided into the following four groups: 1) control group; 2) Cd-exposed group; 3) diabetic group; 4) Cd-exposed diabetic group. Cd exposure was established by the administration of 155 ppm CdCl2 in drinking water. After 25 weeks of treatment, serum fasting glucose and insulin were measured. Meanwhile, the liver and pancreas specimens were sectioned and stained with Hematoxylin and eosin. Gluconeogenesis, glycolysis, lactate concentration and fibrosis in liver were evaluated. Results Clinical signs attributable to diabetes were more apparent in Cd-exposed diabetic mice. Interestingly, Cd exposure significantly decreased fasting blood glucose levels in diabetic group. We further demonstrated that the glycolysis related hepatic enzymes, pyruvate kinase M2 (PKM-2) and lactic dehydrogenase A (LDHA) were both increased, while the gluconeogenesis related hepatic enzymes, phosphoenolpyruvate-1 (PCK-1) and glucose-6-phosphatase (G6Pase) were both decreased in Cd exposed diabetic mice, indicating that Cd increased glycolysis and inhibited gluconeogenesis in diabetic model. Moreover, lactate accumulation was noted accompanied by the increased inflammation and fibrosis in the livers of diabetic mice following Cd exposure. Conclusions Cd exposure disturbed glucose metabolism and exacerbated diabetes, providing a biological relevance that DM patients are at greater risk when exposed to Cd.

scholarly journals Revealing the Hypoglycemic Effects and Mechanism of GABA-Rich Germinated Adzuki Beans on T2DM Mice by Untargeted Serum Metabolomics

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiujie Jiang ◽  
Qingpeng Xu ◽  
Aiwu Zhang ◽  
Yong Liu ◽  
Zhijiang Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Metabolic Pathways ◽  
Fasting Blood Glucose ◽  
Pathway Enrichment Analysis ◽  
Model Assessment ◽  
Public Attention ◽  
Glucose Levels ◽  
Blood Glucose Levels

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic diseases, and exploring strategies to prevent and treat diabetes has become extremely important. In recent decades the search for new therapeutic strategies for T2DM involving dietary interventions has attracted public attention. We established a diabetic mouse model by feeding mice a high-fat diet combined with injection of low-dose streptozotocin, intending to elucidate the effects and possible mechanisms of different dosages of γ-aminobutyric acid (GABA)-rich germinated adzuki beans on the treatment of diabetes in mice. The mice were treated for 6 weeks either with increasing doses of GABA-enriched germinated adzuki beans, with non-germinated adzuki beans, with GABA, or with the positive control drug metformin. Then, the blood glucose levels and blood lipid biochemical indicators of all the mice were measured. At the same time, serum differential metabolite interactions were explored by UPLC-Q/TOF-MS-based serum metabolomic analysis. The results showed that body weight and fasting blood glucose levels were significantly reduced (P &lt; 0.05). We also report improved levels of total cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, urea, and serum creatinine. We observed a significant improvement in the homeostasis model assessment of the beta cell function and insulin resistance (HOMA-β and HOMA-IR) scores (P &lt; 0.05) in the group of mice treated with the highest dose of GABA-enriched germinated adzuki beans. In addition, the metabolic profiles of the serum were analyzed, and 31 differential metabolites including amino acids and lipids were obtained. According to the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, this was found to be correlated with nine significantly enriched metabolic pathways involving the up-regulation of levels of L-serine, SM (d18:1/22:1(13Z)), L-histidine, creatine, and 3-indoleacetic acid. Our data suggest that the hypoglycemic effect of GABA-enriched germinated adzuki beans on diabetic mice may be related to improving tryptophan metabolism, glycerol phospholipid metabolism, sphingosline metabolism, and the glycine, serine, and threonine metabolic pathways. This study provides a reference for the application of GABA-enriched germinated foods in type 2 diabetes and could provide a cue for searching biomarkers to be adopted for T2DM diagnosis.

scholarly journals Meditation Programs for Adults with Type 2 Diabetes Mellitus: Protocol for a Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Manxue Mei ◽  
◽  
Min Jiang ◽  
Zunjiang Li ◽  
Wei Zhu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Meta Analysis ◽  
Fasting Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Review Question

Review question / Objective: Would meditation programs affect fasting blood glucose levels and HbA(1c) of patients with type 2 diabetes mellitus? Would meditation programs intervention be of benefit for remission of depression and anxiety level? Would meditation programs improve quality of life of individuals with type 2 diabetes？ Do meditation programs affect body mass index (BMI), serum lipid levels and level of blood pressure? Which type of meditation programs is better for type 2 diabetes patients? Are there any differences of efficacy among different meditation programs? To provide valid evidence for the effect of meditation programs for type 2 diabetes by synthesizing and comparing outcomes from clinical trials. Main outcome(s): The outcomes include fasting blood glucose levels and HbA(1c).

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