Journal
CURRENT DIABETES REPORTS
Volume 10, Issue 1, Pages 70-77Publisher
CURRENT MEDICINE GROUP
DOI: 10.1007/s11892-009-0087-5
Keywords
Bile acid receptor; Bile acid sequestrant; Cholesterol; Glucose control; Lipid control; Type 2 diabetes mellitus
Categories
Funding
- Daiichi Sankyo, Inc
- GlaxoSmithKline
- Novo Nordisk
- Takeda Pharmaceuticals
- Medtronic
- Merck
- Xoma
- Tethys
- Bristol-Myers Squibb
- AstraZeneca
- Pfizer
- sanofi-aventis
- Eli Lilly
- US National Institutes of Health
- American Diabetes Association
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Bile acids are generated in the liver and are traditionally recognized for their regulatory role in multiple metabolic processes including bile acid homeostasis, nutrient absorption, and cholesterol homeostasis. Recently, bile acids emerged as signaling molecules that, as ligands for the bile acid receptors farnesoid X receptor (FXR) and TGR5, activate and integrate multiple complex signaling pathways involved in lipid and glucose metabolism. Bile acid sequestrants are pharmacologic molecules that bind to bile acids in the intestine resulting in the interruption of bile acid homeostasis and, consequently, reduction in low-density lipoprotein cholesterol levels in hypercholesterolemia. Bile acid sequestrants also reduce glucose levels and improve glycemic control in persons with type 2 diabetes mellitus (T2DM). This article examines the mechanisms by which bile acid-mediated activation of FXR and TGR5 signaling pathways regulate lipid and glucose metabolism and the potential implications for bile acid sequestrant-mediated regulation of lipid and glucose levels in T2DM.
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