scholarly journals Glucose-Sensing Transcription Factor MondoA/ChREBP as Targets for Type 2 Diabetes: Opportunities and Challenges

2019 ◽  
Vol 20 (20) ◽  
pp. 5132 ◽  
Author(s):  
Ziyi Song ◽  
Hao Yang ◽  
Lei Zhou ◽  
Fajun Yang

The worldwide increase in type 2 diabetes (T2D) is becoming a major health concern, thus searching for novel preventive and therapeutic strategies has become urgent. In last decade, the paralogous transcription factors MondoA and carbohydrate response element-binding protein (ChREBP) have been revealed to be central mediators of glucose sensing in multiple metabolic organs. Under normal nutrient conditions, MondoA/ChREBP plays vital roles in maintaining glucose homeostasis. However, under chronic nutrient overload, the dysregulation of MondoA/ChREBP contributes to metabolic disorders, such as insulin resistance (IR) and T2D. In this review, we aim to provide an overview of recent advances in the understanding of MondoA/ChREBP and its roles in T2D development. Specifically, we will briefly summarize the functional similarities and differences between MondoA and ChREBP. Then, we will update the roles of MondoA/ChREBP in four T2D-associated metabolic organs (i.e., the skeletal muscle, liver, adipose tissue, and pancreas) in physiological and pathological conditions. Finally, we will discuss the opportunities and challenges of MondoA/ChREBP as drug targets for anti-diabetes. By doing so, we highlight the potential use of therapies targeting MondoA/ChREBP to counteract T2D and its complications.

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2749 ◽  
Author(s):  
Miguel A. Ortega ◽  
Oscar Fraile-Martínez ◽  
Irene Naya ◽  
Natalio García-Honduvilla ◽  
Melchor Álvarez-Mon ◽  
...  

Obesity is a condition of rising prevalence worldwide, with important socioeconomic implications, being considered as a growing public health concern. Frequently, obesity brings other complications in addition to itself—like Type 2 Diabetes Mellitus (T2DM)—sharing origin, risk factors and pathophysiological mechanisms. In this context, some authors have decided to include both conditions as a unique entity known as “diabesity”. In fact, understanding diabesity as a single disease is possible to maximise the benefits from therapies received in these patients. Gut microbiota plays a key role in individual’s health, and their alterations, either in its composition or derived products are related to a wide range of metabolic disorders like T2DM and obesity. The present work aims to collect the different changes reported in gut microbiota in patients with T2DM associated with obesity and their possible role in the onset, development, and establishment of the disease. Moreover, current research lines to modulate gut microbiota and the potential clinical translation derived from the knowledge of this system will also be reviewed, which may provide support for a better clinical management of such a complex condition.


Author(s):  
L. A. Kharitonova ◽  
O. V. Papisheva ◽  
T. A. Mayatskaya ◽  
G. A. Kotaysh

The gut microbiota has attracted increasing attention during the last several years as a key player in the pathophysiology of chronic disease. Microbiome is considered to be the link between metabolic disorders, obesity, insulin resistance, dyslipidemia, diabetes, hypertension and cardiovascular diseases. Recent findings have related the intestinal microbiota to a plethora of pathological conditions, including type 2 diabetes, obesity, cholelithiasis and nonalcoholic steatohepatitis. This review presents potential mechanisms for the development of these diseases in response to changes in the gut microbiota. They involve increased gut permeability, low-grade inflammation and autoantibodies. Many studies contradict each other, which confirms the need for further scientific research in this area.


Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1874-P
Author(s):  
BIN JIANG ◽  
HUAIJIE WANG ◽  
WEI-YU WANG ◽  
QINGTAO YAN ◽  
MEI-HUA QU ◽  
...  

2019 ◽  
Vol 25 (23) ◽  
pp. 2602-2606 ◽  
Author(s):  
Shahzad Khan ◽  
Mohammad A. Kamal

: Insulin resistance and type 2 Diabetes mellitus resulting in chronic hyperglycemia is a major health problem in the modern world. Many drugs have been tested to control hyperglycemia which is believed to be the main factor behind many of the diabetes-related late-term complications. Wogonin is a famous herbal medicine which has been shown to be effective in controlling diabetes and its complications. In our previous work, we showed that wogonin is beneficial in many ways in controlling diabetic cardiomyopathy. In this review, we mainly explained wogonin anti-hyperglycemic property through AKT/GLUT4 pathway. Here we briefly discussed that wogonin increases Glut4 trafficking to plasma membrane which allows increased entry of glucose and thus alleviates hyperglycemia. Conclusion: Wogonin can be used as an anti-diabetic and anti-hyperglycemic drug and works via AKT/GLUT4 pathway.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Ada Krawęcka ◽  
Aldona Sobota ◽  
Emilia Sykut-Domańska

Type 2 diabetes has become one of the major health problems of the modern world. It is assumed that environmental factors have a significant impact on the development of the disease, and great importance is ascribed to the diet, which can be modified accordingly. The diet can exert prophylactic and therapeutic effects; changes in the diet in advanced disease can improve the quality of life of diabetic patients and minimise the risk of complications, which are the direct cause of diabetes-related death. Functional food, which has a potentially health-enhancing effect in addition to its nutritional value, has been increasingly recognised and required. Cereal products are crucial in diabetic nutrition. Their function can additionally be enhanced by fortification with compounds with proven hypoglycaemic effects. Pasta has a low glycaemic index and is a good carrier of fortifying substances; hence, it can be highly recommended in diets for diabetic patients.


2021 ◽  
Vol 22 (7) ◽  
pp. 3566
Author(s):  
Chae Bin Lee ◽  
Soon Uk Chae ◽  
Seong Jun Jo ◽  
Ui Min Jerng ◽  
Soo Kyung Bae

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1460
Author(s):  
Kalliopi Karatzi ◽  
Yannis Manios

Type 2 diabetes (T2DM) and hypertension are major health problems, with an undisputed growth burden in the past decades [...]


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Amara ◽  
R Ghammem ◽  
N Zammit ◽  
S BenFredj ◽  
J Maatoug ◽  
...  

Abstract Introduction Diabetes mellitus is a growing public health concern. Despite compelling evidence about the effectiveness of medications, studies have indicated that less than 50% of patients achieved therapeutic targets. The aim of this study was to assess the adherence to type 2 diabetes mellitus treatment and its determinants. Methods A cross-sectional study was conducted between April and June 2017 in the Endocrinology and internal medicine departments of Farhat Hached University Hospital in Sousse, Tunisia. A convenient sample of patients who fulfilled the eligibility criteria was recruited. A pre-tested questionnaire was used to gather information. This was followed by assessing patients' adherence to diabetes medications using the eight-item Morisky Medication Adherence Scale (MMAS-8). Results A total of 330 patients with Type 2 Diabetes Mellitus participated in this study. The mean ±SD age of patients was 58.96±10.3 with female predominance (60.3%). More than half of participants were with high cardiovascular risk. In most cases (70.6 %), participants were moderate adherent. Results showed that patients become non-adherent as the disease gets older (p = 0.001). In addition patients with health insurance were significantly more adherent comparing to those who did not have it (p = 0.01). Regarding self-care practices and other metabolic risk factors' effects, our data revealed that exercising 30 minutes below than 5 times in week and poor self-management of diet were associated with low adherence (p < 10-3). On the other hand, patients who have started insulin therapy were less adherent than those who had not yet (0.01). Patients with diabetic retinopathy or maculopathy were significantly more prone to be non- adherent, with respective percentage of 39.1% and 37.5%. Conclusions This study provides insights into the determinants of non-adherence, ultimately guiding the effective interventions through development of structured long-term policies not yet implemented. Key messages In most cases (70.6 %), participants were moderate adherent. Patients with diabetic retinopathy or maculopathy were significantly more prone to be non- adherent.


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