scholarly journals Hyocholic acid species and the risk of type 2 diabetes

2018 ◽  
Author(s):  
Xiaojiao Zheng ◽  
Tianlu Chen ◽  
Runqiu Jiang ◽  
Aihua Zhao ◽  
Fengjie Huang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Mouse ◽  
Farnesoid X Receptor ◽  
Lower Serum ◽  
Obesity And Diabetes ◽  
Hyocholic Acid ◽  
G Protein Coupled ◽  
Unique Mechanism ◽  
Apparently Healthy

ABSTRACTHyocholic acid (HCA) and its derivatives are found in only trace amounts in human blood, but constitute approximately 76 % of the bile acid (BA) pool in the pig, a species known for its exceptional resistance to type 2 diabetes mellitus (T2DM). Here we show that HCA species play a crucial role in maintaining glucose homeostasis and preventing T2DM. We found that in two cohort studies (n=1,213), both obesity and diabetes were associated with lower serum concentrations of HCA species. Serum HCA levels in apparently healthy individuals (n=132) were found to be strong predictors for metabolic health 10 years later. Oral administration of HCA increased serum fasting GLP-1, to a greater extent than metformin, in healthy and diabetic mouse models. HCA upregulated GLP-1 secretion in intestinal enteroendocrine cells via simultaneously activating G-protein-coupled BA receptor, TGR5, and inhibiting farnesoid X receptor, a unique mechanism that is not found in other BA species.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Bile acid sequestrants in type 2 diabetes: potential effects on GLP1 secretion

2014 ◽  
Vol 171 (2) ◽  
pp. R47-R65 ◽  
Author(s):  
David P Sonne ◽  
Morten Hansen ◽  
Filip K Knop
Keyword(s):  
Type 2 Diabetes ◽  
Bile Acid ◽  
Bile Acids ◽  
G Protein ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Bile Acid Sequestrants ◽  
G Protein Coupled

Bile acid sequestrants have been used for decades for the treatment of hypercholesterolaemia. Sequestering of bile acids in the intestinal lumen interrupts enterohepatic recirculation of bile acids, which initiate feedback mechanisms on the conversion of cholesterol into bile acids in the liver, thereby lowering cholesterol concentrations in the circulation. In the early 1990s, it was observed that bile acid sequestrants improved glycaemic control in patients with type 2 diabetes. Subsequently, several studies confirmed the finding and recently – despite elusive mechanisms of action – bile acid sequestrants have been approved in the USA for the treatment of type 2 diabetes. Nowadays, bile acids are no longer labelled as simple detergents necessary for lipid digestion and absorption, but are increasingly recognised as metabolic regulators. They are potent hormones, work as signalling molecules on nuclear receptors and G protein-coupled receptors and trigger a myriad of signalling pathways in many target organs. The most described and well-known receptors activated by bile acids are the farnesoid X receptor (nuclear receptor) and the G protein-coupled cell membrane receptor TGR5. Besides controlling bile acid metabolism, these receptors are implicated in lipid, glucose and energy metabolism. Interestingly, activation of TGR5 on enteroendocrine L cells has been suggested to affect secretion of incretin hormones, particularly glucagon-like peptide 1 (GLP1 (GCG)). This review discusses the role of bile acid sequestrants in the treatment of type 2 diabetes, the possible mechanism of action and the role of bile acid-induced secretion of GLP1 via activation of TGR5.

scholarly journals Gut Microbiome of Indonesian Adults Associated with Obesity and Type 2 Diabetes: A Cross-Sectional Study in an Asian City, Yogyakarta

2021 ◽  
Vol 9 (5) ◽  
pp. 897
Author(s):  
Phatthanaphong Therdtatha ◽  
Yayi Song ◽  
Masaru Tanaka ◽  
Mariyatun Mariyatun ◽  
Maisaroh Almunifah ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bile Acids ◽  
Gut Microbiome ◽  
Dietary Habits ◽  
Lifestyle Changes ◽  
Farnesoid X Receptor ◽  
Triangular Distribution ◽  
Obese People ◽  
Obesity And Diabetes

Indonesia is a developing country facing the national problem of the growing obesity and diabetes in its population due to recent drastic dietary and lifestyle changes. To understand the link between the gut microbiome, diet, and health of Indonesian people, fecal microbiomes and metabolomes of 75 Indonesian adults in Yogyakarta City, including obese people (n = 21), type 2 diabetes (T2D) patients (n = 25), and the controls (n = 29) were characterized together with their dietary and medical records. Variations of microbiomes showed a triangular distribution in the principal component analysis, driven by three dominant bacterial genera, namely Bacteroides, Prevotella, and Romboutsia. The Romboutsia-driven microbiome, characterized by low bacterial diversity and high primary bile acids, was associated with fat-driven obesity. The Bacteroides-driven microbiome, which counteracted Prevotella but was associated with Ruminococcaceae concomitantly increased with high-carbohydrate diets, showed positive correlation with T2D indices but negative correlation with body mass index. Notably, Bacteroides fragilis was increased in T2D patients with a decrease in fecal conjugated bile acids, particularly tauroursodeoxycholic acid (TUDCA), a farnesoid X receptor (FXR) antagonist with anti-diabetic activity, while these features disappeared in patients administered metformin. These results indicate that the gut microbiome status of Indonesian adults is differently associated with obesity and T2D under their varied dietary habits.

scholarly journals Gut Microbiome of Indonesian Adults Differently Associated with Obesity and type 2 Diabetes under Varied Dietary Habits: A Cross-sectional Study in an Asian Developing City, Yogyakarta

2020 ◽  
Author(s):  
Phatthanaphong Therdtatha ◽  
Yayi Song ◽  
Masaru Tanaka ◽  
Mariyatun Mariyatun ◽  
Miisaroh Almunifah ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bile Acids ◽  
Gut Microbiome ◽  
Dietary Habits ◽  
Lifestyle Changes ◽  
Farnesoid X Receptor ◽  
Triangular Distribution ◽  
Obese People ◽  
Obesity And Diabetes

Abstract Indonesia is a developing country facing the national problem of the growing obesity and diabetes in its population due to recent drastic dietary and lifestyle changes. To understand the interface between the gut microbiome, diet, and health of Indonesian people, we characterized fecal microbiomes and metabolomes of 75 Indonesian adults in Yogyakarta City, including 21 obese people and 25 type 2 diabetes (T2D) patients, together with their dietary and medical records. Variations of microbiomes showed a triangular distribution in the principal component analysis, driven by three dominant bacterial genera, namely Bacteroides, Prevotella, and Romboutsia. The Romboutsia-driven microbiome, characterized by low bacterial diversity and high primary bile acids, was associated with fat-driven obesity. The Bacteroides-driven microbiome, which counteracted Prevotella but was associated with Ruminococcaceae concomitantly increased with high-carbohydrate diets, showed positive correlation with T2D indices but negative correlation with body mass index. Notably, Bacteroides fragilis was increased in T2D patients with a decrease of fecal conjugated bile acids, particularly tauroursodeoxycholic acid, a farnesoid X receptor antagonist with anti-diabetic activity, while these features disappeared in patients administered metformin. These results indicate that the gut microbiome status of Indonesian adults is differently associated with obesity and T2D under their varied dietary habits.

The Role of Physical Exercise in Obesity and Diabetes

2018 ◽  
Vol 66 (3) ◽  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Physical Exercise ◽  
Treatment Guidelines ◽  
Treatment Guideline ◽  
Obesity And Diabetes ◽  
Regular Physical Exercise

The prevalence of obesity is increasing world-wide. Obesity is associated with a plethora of metabolic and clinical constraints, which result in a higher risk for the development of cardiovascular complications and metabolic disease, particularly insulin resistance and type 2 diabetes. Obesity is an acknowledged determinant of glycemic control in patients with type 1 diabetes and accounts for the majority of premature death due to cardiovascular events. Physical exercise is generally recommended in patients with diabetes in order to prevent the development of or reduce existing obesity, as adopted by every international treatment guideline so far. Regular physical exercise has a beneficial impact on body composition, cardiovascular integrity, insulin sensitivity and quality of life. However, only a minority of patients participates in regular physical exercise, due to individual or ­disease-related barriers. In type 2 diabetes, there is robust evidence for beneficial effects of physical exercise on glycemic control, cardiovascular health and the development of diabetes-related long-term complications. In type 1 diabetes and patients treated with insulin, a higher risk for exercise-­related hypoglycemia has to be considered, which requires certain prerequisites and adequate adaptions of insulin ­dosing. Current treatment guidelines do only incompletely address the development of exercise-related hypoglycemia. However, every patient with diabetes should participate in regular physical exercise in order to support and enable ­sufficient treatment and optimal glycemic control.

Discovery of a potent G-protein-coupled receptor 119 agonist for the treatment of type 2 diabetes

2021 ◽  
Vol 35 ◽  
pp. 116071
Author(s):  
Suresh Pola ◽  
Shailesh R. Shah ◽  
Harikishore Pingali ◽  
Pandurang Zaware ◽  
Baban Thube ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Immunometabolism of obesity and diabetes: microbiota link compartmentalized immunity in the gut to metabolic tissue inflammation

2015 ◽  
Vol 129 (12) ◽  
pp. 1083-1096 ◽  
Author(s):  
Joseph B. McPhee ◽  
Jonathan D. Schertzer
Keyword(s):  
Metabolic Disease ◽  
Type 2 Diabetes ◽  
Immune Responses ◽  
Metabolic Diseases ◽  
The Body ◽  
Tissue Inflammation ◽  
Gut Barrier Function ◽  
Inflammatory Status ◽  
Obesity And Diabetes

The bacteria that inhabit us have emerged as factors linking immunity and metabolism. Changes in our microbiota can modify obesity and the immune underpinnings of metabolic diseases such as Type 2 diabetes. Obesity coincides with a low-level systemic inflammation, which also manifests within metabolic tissues such as adipose tissue and liver. This metabolic inflammation can promote insulin resistance and dysglycaemia. However, the obesity and metabolic disease-related immune responses that are compartmentalized in the intestinal environment do not necessarily parallel the inflammatory status of metabolic tissues that control blood glucose. In fact, a permissive immune environment in the gut can exacerbate metabolic tissue inflammation. Unravelling these discordant immune responses in different parts of the body and establishing a connection between nutrients, immunity and the microbiota in the gut is a complex challenge. Recent evidence positions the relationship between host gut barrier function, intestinal T cell responses and specific microbes at the crossroads of obesity and inflammation in metabolic disease. A key problem to be addressed is understanding how metabolite, immune or bacterial signals from the gut are relayed and transferred into systemic or metabolic tissue inflammation that can impair insulin action preceding Type 2 diabetes.

scholarly journals Farnesoid X Receptor an Emerging Target to Combat Obesity

2017 ◽  
Vol 35 (3) ◽  
pp. 185-190 ◽  
Author(s):  
C. Daniel De Magalhaes Filho ◽  
Michael Downes ◽  
Ronald M. Evans
Keyword(s):  
Type 2 Diabetes ◽  
Bile Acid ◽  
Treatment Options ◽  
Farnesoid X Receptor ◽  
Whole Body ◽  
Body Lipid ◽  
Associated Diseases ◽  
Attractive Candidate ◽  
Potential Use

Obesity and its associated diseases, including type 2 diabetes, have reached epidemic levels worldwide. However, available treatment options are limited and ineffective in managing the disease. There is therefore an urgent need for the development of new pharmacological solutions. The bile acid (BA) Farnesoid X receptor (FXR) has recently emerged as an attractive candidate. Initially described for their role in lipid and vitamin absorption from diet, BAs are hormones with powerful effects on whole body lipid and glucose metabolism. In this review, we focus on FXR and how 2 decades of work on this receptor, both in rodents and humans, have led to the development of drug agonists with potential use in humans for treatment of conditions ranging from obesity-associated diseases to BA dysregulation.

scholarly journals Quinoa’s Potential to Enhance Dietary Management of Obesity and Type-2 Diabetes: A Review of the Current Evidence

Diabetology ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 77-94
Author(s):  
Alexander Little ◽  
Kevin Murphy ◽  
Patrick Solverson
Keyword(s):  
Type 2 Diabetes ◽  
Best Management Practices ◽  
Management Practices ◽  
The United States ◽  
Lipid Absorption ◽  
Current Evidence ◽  
Future Research ◽  
Dietary Management ◽  
Obesity And Diabetes

The prevalence of diet-induced obesity and type-2 diabetes remains a growing concern in the United States. As best management practices still include improved diet and physical activity, bioactive food components, contained within functional foods, show promise in curbing the cardiometabolic complications associated with excess weight and diabetes. Quinoa is an emerging candidate crop for its versatility in wide-ranging growing conditions as one approach to address food security, but it also contains several components that may serve as a dietary tool for post-industrial countries struggling with the health complications of caloric excess. Preliminary rodent feeding studies demonstrate that components within quinoa, namely, phytosteroids, phenolics, polysaccharides, and peptides, can prevent adiposity, dyslipidemia, and hyperglycemia. Mechanistic activity may involve reduced lipid absorption and adipogenesis, increased energy expenditure and glucose oxidation and corrected gut microbiota. Other intestinal actions may include blocked carbohydrate digestion with enhanced incretin signaling. Evidence in clinical trials is lacking and future research spanning cells to the clinic is needed to further elucidate the interesting preliminary reports reviewed here. Quinoa offers several unique attributes that could be harnessed to improve the dietary management of obesity and diabetes.

scholarly journals Discovery of MK-8282 as a Potent G-Protein-Coupled Receptor 119 Agonist for the Treatment of Type 2 Diabetes

2018 ◽  
Vol 9 (5) ◽  
pp. 457-461 ◽  
Author(s):  
Santhosh F. Neelamkavil ◽  
Andrew W. Stamford ◽  
Timothy Kowalski ◽  
Dipshikha Biswas ◽  
Craig Boyle ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Role of folate in nonalcoholic fatty liver disease

2017 ◽  
Vol 95 (10) ◽  
pp. 1141-1148 ◽  
Author(s):  
Victoria Sid ◽  
Yaw L. Siow ◽  
Karmin O
Keyword(s):  
Type 2 Diabetes ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Serum Folate ◽  
Nonalcoholic Fatty Liver ◽  
Obesity And Diabetes

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD.

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