Article

A review of bile acid sequestrants: potential mechanism(s) for glucose-lowering effects in type 2 diabetes mellitus.

Universite Lille Nord de France, Inserm U545, UDSL, Lille, France.
Postgraduate Medicine (impact factor: 1.78). 06/2009; 121(3 Suppl 1):25-30. DOI:10.3810/pgm.2009.05.suppl53.290 pp.25-30
Source: PubMed

ABSTRACT Clinical evidence has demonstrated that bile acid sequestrants reduce glucose levels in patients with type 2 diabetes mellitus (T2DM). This effect has been confirmed in multiple double-blind, placebo-controlled clinical studies with the bile acid sequestrant colesevelam hydrochloride (HCl). Colesevelam HCl was approved by the US Food and Drug Administration in January 2008 as an adjunctive therapy for patients with T2DM to improve glycemic control. However, the mechanism of action for the glucose-lowering effect of bile acid sequestrants is unclear. Bile acid sequestrants are nonsystemic pharmacological agents that bind bile acids in the gastrointestinal tract, thereby diverting bile acids from the enterohepatic circulation. This, in turn, upregulates bile acid synthesis (via cholesterol 7-alpha-hydroxylase), which utilizes cholesterol, resulting in reduced low-density lipoprotein cholesterol levels. Recent research has revealed that bile acids are tightly controlled signaling molecules that have metabolic effects beyond their primary role in bile to aid in the digestion of lipids and fat. Bile acids signal via various membrane and nuclear receptors. Therefore, bile acid sequestrants may exert glycemic effects by altering the interaction of these bile acid pathways. This article reviews the role for bile acids in glucose regulation and discusses the potential mechanism(s) of action for the glycemic effects of bile acid sequestrants.

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Keywords

article reviews
 
bile acid pathways
 
bile acid sequestrant colesevelam hydrochloride
 
bile acid sequestrants
 
bile acids
 
Bile acids signal
 
bind bile acids
 
Colesevelam HCl
 
Drug Administration
 
enterohepatic circulation
 
glucose regulation
 
glucose-lowering effect
 
glycemic effects
 
metabolic effects
 
multiple double-blind
 
placebo-controlled clinical studies
 
potential mechanism(s)
 
type 2 diabetes mellitus
 
upregulates bile acid synthesis
 
utilizes cholesterol
 

Bart Staels