Bile acids and their effects on diabetes.
10.1007/s11684-018-0644-x
- Author:
Cynthia RAJANI
1
;
Wei JIA
2
Author Information
1. University of Hawaii Cancer Center, Honolulu, HI, 96813, USA.
2. University of Hawaii Cancer Center, Honolulu, HI, 96813, USA. wjia@cc.hawaii.edu.
- Publication Type:Journal Article
- Keywords:
bariatric surgery;
bile acids;
circadian rhythm;
diabetes;
metabolic memory
- MeSH:
Animals;
Bile Acids and Salts;
blood;
metabolism;
Blood Glucose;
drug effects;
metabolism;
Circadian Rhythm;
Diabetes Mellitus;
blood;
drug therapy;
metabolism;
Energy Metabolism;
Homeostasis;
Humans;
Hyperglycemia;
metabolism;
physiopathology;
Hypoglycemic Agents;
therapeutic use;
Intestinal Mucosa;
metabolism;
Intestines;
drug effects;
Lipid Metabolism;
Liver;
drug effects;
metabolism;
Receptors, Cytoplasmic and Nuclear;
metabolism;
Receptors, G-Protein-Coupled;
metabolism;
Signal Transduction
- From:
Frontiers of Medicine
2018;12(6):608-623
- CountryChina
- Language:English
-
Abstract:
Diabetes is a widespread, rapidly increasing metabolic disease that is driven by hyperglycemia. Early glycemic control is of primary importance to avoid vascular complications including development of retinal disorders leading to blindness, end-stage renal disease, and accelerated atherosclerosis with a higher risk of myocardial infarction, stroke and limb amputations. Even after hyperglycemia has been brought under control, "metabolic memory," a cluster of irreversible metabolic changes that allow diabetes to progress, may persist depending on the duration of hyperglycemia. Manipulation of bile acid (BA) receptors and the BA pool have been shown to be useful in establishing glycemic control in diabetes due to their ability to regulate energy metabolism by binding and activating nuclear transcription factors such as farnesoid X receptor (FXR) in liver and intestine as well as the G-protein coupled receptor, TGR5, in enteroendocrine cells and pancreatic β-cells. The downstream targets of BA activated FXR, FGF15/21, are also important for glucose/insulin homeostasis. In this review we will discuss the effect of BAs on glucose and lipid metabolism and explore recent research on establishing glycemic control in diabetes through the manipulation of BAs and their receptors in the liver, intestine and pancreas, alteration of the enterohepatic circulation, bariatric surgery and alignment of circadian rhythms.
