Effects of Chenodeoxycholic Acid on the Secretion of Gut Peptides and Fibroblast Growth Factors in Healthy Humans

Meyer‐Gerspach, Anne Christin; Steinert, Robert E.; Keller, Sylvia; Malarski, Angelika; Schulte, Felix; Beglinger, C.

doi:10.1210/jc.2012-4109

Cited by 46 publications

(45 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Already in the 1980s, there were reports of bileinduced secretion of GIP (54,55) and glucagon-like reactive materials in dogs (46,57,58,59) and insulin (60). Since then, various groups have reported similar findings (13, 61,62,63,64).…”

Section: Glp1 Secretionmentioning

confidence: 61%

See 1 more Smart Citation

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

Sonne

Hansen

Knop

2014

European Journal of Endocrinology

View full text Add to dashboard Cite

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.

show abstract

Section: Glp1 Secretionmentioning

confidence: 61%

“…Indeed, Sato et al (207) has recently demonstrated, in a study in dogs, that biliary diversion to the ileum increases the secretion of the L cell product PYY. Recently, the results from several human studies have supported a role for bile-induced secretion of GLP1 (13, 61,62,63,64).…”

Section: Tgr5-dependent Mechanismsmentioning

confidence: 99%

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

Sonne

Hansen

Knop

2014

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Nevertheless, our observation that BAs positively correlate with FGF19 and not GLP-1 raises the interesting possibility that the post-RYGB effects of BAs may occur predominantly through FXR rather than TGR5. Consistent with this hypothesis, Meyer-Gerspach et al demonstrated that a physiological load of CDCA is a weak stimulus for GLP-1 with no insulinotropic GLP-1 dependent effects on glucose homeostasis or appetite perceptions [41]. Instead, intraduodenal infusion of CDCA resulted in an impressive dose-dependent increase in FGF19 and attenuated insulin release after an OGTT, leading them to similarly implicate the FXR pathway as the predominant means through which BAs exert glycemic control.…”

Section: Discussionmentioning

confidence: 98%

FGF 19 and Bile Acids Increase Following Roux-en-Y Gastric Bypass but Not After Medical Management in Patients with Type 2 Diabetes

et al. 2015

View full text Add to dashboard Cite

Purpose To quantify changes in fibroblast growth factor 19 (FGF19) and bile acids (BAs) in patients with uncontrolled type 2 diabetes randomized to Roux-en-Y gastric bypass (RYGB) vs intensive medical management (IMM) and matched for similar reduction in HbA1c after 1 year of treatment. Materials and Methods Blood samples were drawn from patients who underwent a test meal challenge before and 1 year after IMM (n=15) or RYGB (n=15). Results Mean HbA1c decreased from 9.7 to 6.4% after RYGB and from 9.1 to 6.1% in the IMM group. At 12 mo the number of diabetes medications used per subject in the RYGB group (2.5 ± 0.5) was less than in the IMM group (4.6 ± 0.3). After RYGB FGF19 increased in the fasted (93±15 to 152±19 pg/ml; P=0.008) and postprandial states (AUC, 10.8 ± 1.9 to 23.4 ± 4.1 pg × hr/ml × 103; P=0.006) but remained unchanged following IMM. BAs increased after RYGB (AUC × 103, 6.63 ± 1.3 to 15.16 ± 2.56 M × h; P=0.003) and decreased after IMM (AUC × 103 8.22 ±1.24 to 5.70 ± 0.70; P=0.01). No changes were observed in the ratio of 12α-hydroxylated/non-12α-hyroxylated BAs. Following RYGB, FGF19 AUC correlated with BAs (r=0.54, P=0.04) and trended negatively with HbA1c (r=−0.44; P=0.09); these associations were not observed after IMM. Conclusion BA and FGF19 levels increased after RYGB but not after IMM in subjects who achieved similar improvement in glycemic control. Further studies are necessary to determine whether these hormonal changes facilitate improved glucose homeostasis.

show abstract

“…It can induce the activation of TGR5, and release of gut peptides. Meyer-Gerspach et al (37) have reported that intestinal infusion of CDCA can mimic physiological concentrations and result in a small but significant increase of both GLP-1 and CCK secretion. They observed a significantly attenuated C peptide as well as insulin response after the OGTT with 15 mmol/L CDCA.…”

Section: Discussionmentioning

confidence: 99%

Chenodeoxycholic Acid as a Potential Prognostic Marker for Roux-en-Y Gastric Bypass in Chinese Obese Patients

Bao

et al. 2015

The Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

show abstract

Effects of Chenodeoxycholic Acid on the Secretion of Gut Peptides and Fibroblast Growth Factors in Healthy Humans

Cited by 46 publications

References 41 publications

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

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

FGF 19 and Bile Acids Increase Following Roux-en-Y Gastric Bypass but Not After Medical Management in Patients with Type 2 Diabetes

Chenodeoxycholic Acid as a Potential Prognostic Marker for Roux-en-Y Gastric Bypass in Chinese Obese Patients

Contact Info

Product

Resources

About