scholarly journals Grainyhead 1 acts as a drug-inducible conserved transcriptional regulator linked to insulin signaling and lifespan

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Giovanna Grigolon ◽  
Elisa Araldi ◽  
Reto Erni ◽  
Jia Yee Wu ◽  
Carolin Thomas ◽  
...  

AbstractAging is impacted by interventions across species, often converging on metabolic pathways. Transcription factors regulate longevity yet approaches for their pharmacological modulation to exert geroprotection remain sparse. We show that increased expression of the transcription factor Grainyhead 1 (GRH-1) promotes lifespan and pathogen resistance in Caenorhabditis elegans. A compound screen identifies FDA-approved drugs able to activate human GRHL1 and promote nematodal GRH-1-dependent longevity. GRHL1 activity is regulated by post-translational lysine methylation and the phosphoinositide (PI) 3-kinase C2A. Consistently, nematodal longevity following impairment of the PI 3-kinase or insulin/IGF-1 receptor requires grh-1. In BXD mice, Grhl1 expression is positively correlated with lifespan and insulin sensitivity. In humans, GRHL1 expression positively correlates with insulin receptor signaling and also with lifespan. Fasting blood glucose levels, including in individuals with type 2 diabetes, are negatively correlated with GRHL1 expression. Thereby, GRH-1/GRHL1 is identified as a pharmacologically malleable transcription factor impacting insulin signaling and lifespan.

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 ◽  
...  

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.


2018 ◽  
Vol 6 (1) ◽  
pp. 85
Author(s):  
Gema Akbar Wakhidana ◽  
Ancah Caesarina Novi Marchianti ◽  
Ali Santosa

Diabetes mellitus is metabolic diseases characterized by hyperglycemia caused by disturbances in insulin secretion or insulin activity. Herbal Forte Rice is rice synthetic material composed of main purple sweet potato and corn flour. It contains antioksidan, fiber, resistant starch and having moderate glycemic index. This study aimed to determine the effectivity of Herbal Forte Rice on decreasing blood glucose levels of patients type 2 DM. It used a cross-over design, the role of research subjects was both as control and treatment groups. Total sample of this research consisted of 60 samples. The treatment group was given Herbal Forte Rice for 7 days in 2 consecutive meals, while the control group did not receive any intervention. The results showed the average level of Fasting Blood Glucose (FBG) beginning and end of the treatment group 179.76 mg/dL and 138.7 mg/dL; FBG beginning and end of the control 180.87 mg/dL and 187.63 mg/dL; 2 hours post prandial Blood Glucose (2hppBG) levels of beginning and end of the treatment group 284.37 mg/dL and 183.8 mg/dL; 2hppBG levels beginning and end of the control 280.57 mg/dL and 284.13 mg/dL. This study concludes that Herbal Forte Rice effective on decreasing blood glucose levels of patients type 2 DM.   Keywords: diabetes mellitus, Rice Herbal Forte, GDP and GD2PP  


2021 ◽  
Author(s):  
Mengyang Li ◽  
Shuai Wang ◽  
Xiuxiu Liu ◽  
Zhijie Sheng ◽  
Bingyan Li ◽  
...  

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.


2021 ◽  
Vol 8 ◽  
Author(s):  
Xiujie Jiang ◽  
Qingpeng Xu ◽  
Aiwu Zhang ◽  
Yong Liu ◽  
Zhijiang Li ◽  
...  

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.


2021 ◽  
Author(s):  
Manxue Mei ◽  
◽  
Min Jiang ◽  
Zunjiang Li ◽  
Wei Zhu ◽  
...  

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).


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Xinglong Liu ◽  
Wencong Liu ◽  
Chuanbo Ding ◽  
Yingchun Zhao ◽  
Xueyan Chen ◽  
...  

Streptozotocin- (STZ-) induced type 2 diabetes mellitus (T2DM) caused insulin secretion disorder and hyperglycemia, further causing tissue and organ damage. In recent years, studies on ginseng (Panax ginseng C. A. Meyer) and its saponins (Ginsenosides) have proved to possess antidiabetic pharmacological activities, but the mechanism of nonsaponins on STZ-induced T2DM is still unclear. Arginyl-fructosyl-glucose (AFG) is a representative nonsaponin component produced in the processing of red ginseng. The present study was designed to assess the possible healing consequence of AFG on STZ-induced T2DM in mice and also to explore its fundamental molecular contrivances. T2DM-related indexes, fasting blood glucose levels, and body weight, histological changes, biochemical considerations, biomarkers, the mRNA countenance intensities of inflammatory facts, and variations in correlated protein manifestation in adipose tissue and liver tissue were calculated. Consequences specified that AFG usage successfully amends STZ-induced insulin conflict and liver grievance in T2DM. Systematically, AFG action diminished STZ-induced oxidative stress and inflammatory responses in the liver. In addition, we demonstrated that AFG also attenuates apoptosis and insulin secretion disorders in T2DM by adjusting the PI3K/AKT/GSK3β signaling pathway. At the end, these discoveries recommend that AFG averts the development of T2DM through numerous types of machinery and proposes that AFG can also be used in order to treat T2DM in the future.


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