Alterations of Hormonally Active Fibroblast Growth Factors after Roux-en-Y Gastric Bypass Surgery

Jansen, Petér L. M.; Werven, Jochem van; Aarts, Edo O.; Berends, Frits J.; Janssen, Ignace; Stoker, Jaap; Schaap, Frank G.

doi:10.1159/000324128

Cited by 120 publications

(99 citation statements)

References 20 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Also of interest is the as yet untested hypothesis that beneficial metabolic effects of bariatric surgical procedures are tied to increased FGF19 secretion from gut enterocytes. Consistent with this possibility, circulating levels of bile acids (45,46) and FGF19 increase following roux-en-Y gastric bypass (RYGB) surgery in humans (47,48). As bile acid stimulation of FGF19 secretion is mediated via FXR, these data collectively raise the possibility that increased bile acid-induced stimulation of FGF19 secretion (and increased GE) contributes to the high rate of diabetes remission induced by RYGB (49), but a direct test of this hypothesis is still awaited.…”

Section: Discussionmentioning

confidence: 96%

FGF19 action in the brain induces insulin-independent glucose lowering

Morton¹,

Matsen²,

Bracy³

et al. 2013

J. Clin. Invest.

195

183

View full text Add to dashboard Cite

Insulin-independent glucose disposal (referred to as glucose effectiveness [GE]) is crucial for glucose homeostasis and, until recently, was thought to be invariable. However, GE is reduced in type 2 diabetes and markedly decreased in leptin-deficient ob/ob mice. Strategies aimed at increasing GE should therefore be capable of improving glucose tolerance in these animals. The gut-derived hormone FGF19 has previously been shown to exert potent antidiabetic effects in ob/ob mice. In ob/ob mice, we found that systemic FGF19 administration improved glucose tolerance through its action in the brain and that a single, low-dose i.c.v. injection of FGF19 dramatically improved glucose intolerance within 2 hours. Minimal model analysis of glucose and insulin data obtained during a frequently sampled i.v. glucose tolerance test showed that the antidiabetic effect of i.c.v. FGF19 was solely due to increased GE and not to changes of either insulin secretion or insulin sensitivity. The mechanism underlying this effect appears to involve increased metabolism of glucose to lactate. Together, these findings implicate the brain in the antidiabetic action of systemic FGF19 and establish the brain's capacity to rapidly, potently, and selectively increase insulin-independent glucose disposal.

show abstract

Section: Discussionmentioning

confidence: 96%

FGF19 action in the brain induces insulin-independent glucose lowering

Morton¹,

Matsen²,

Bracy³

et al. 2013

J. Clin. Invest.

195

183

View full text Add to dashboard Cite

show abstract

“…However, not all researchers agree on this postulate (121), but, interestingly, it has been proposed that diabetic patients may also exhibit decreased FGF19 signalling and a subsequent impaired FGF19-dependent reduction in bile acid synthesis (121, 188). Lastly, following RYGB surgery, FGF19 concentrations increase, probably reflecting enhanced delivery of bile to the distal intestine and thus increased activation of FXR (21, 189,190). Thus, FGF19 may constitute an important, postprandial enteroendocrine factor -with possible incretin-like actions -regulating hepatic protein and glycogen synthesis and gluconeogenesis (180,184).…”

Section: European Journal Of Endocrinologymentioning

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

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

“…Also, body weight loss and/or calorie restriction have an impact on glucose and BA homeostasis [14,15]. During malabsorptive procedures, such as various types of gastric bypass surgeries performed commonly nowadays, a small pouch is created in the stomach, connecting it with the proximal jejunum.…”

Section: Introductionmentioning

confidence: 99%

Evidence That the Length of Bile Loop Determines Serum Bile Acid Concentration and Glycemic Control After Bariatric Surgery

et al. 2018

View full text Add to dashboard Cite

Background Bariatric surgery contributes to the improvement in glucose metabolism that may be related to a postoperative increase in serum bile acids (BAs). Three commonly used types of bariatric procedures, laparoscopic sleeve gastrectomy (LSG) (without creation of a bile loop), Roux-en-Y gastric bypass (RYGB), and omega-loop gastric bypass (OLGB) (with creation of shorter 100-150 cm and longer 200-280 cm bile loops, respectively), differ in their effects on glycemic control. The aim of the study was to compare the effects of various bariatric procedures on serum BA concentration and glucose homeostasis. Methods Serum BAs in 26 obese patients were determined by liquid chromatography-mass spectrometry prior to bariatric surgery, as well as 4 days and 3 months thereafter. Results Four days after the surgery, serum concentrations of BAs in LSG and OLGB groups were similar as prior to the procedure, and a slight decrease in serum BAs was observed in the RYGB group. Serum BA level in the LSG group remained unchanged also at 3 months after the surgery, whereas a significant 0.5-and 3-fold increase in this parameter was noted in the RYGB and OLGB groups, respectively. Serum concentration of BAs correlated positively with the length of the bile loop (R = 0.47, p < 0.05). Conclusion The evident improvement of glycemic control observed 3 months after OLGB might be associated with a postoperative increase in serum BAs, resulting from their better absorption from the longer bile loop. However, the changes in serum BAs probably had little or no impact on insulin sensitivity improvement at 4 days post-surgery.

show abstract

Alterations of Hormonally Active Fibroblast Growth Factors after Roux-en-Y Gastric Bypass Surgery

Cited by 120 publications

References 20 publications

FGF19 action in the brain induces insulin-independent glucose lowering

FGF19 action in the brain induces insulin-independent glucose lowering

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

Evidence That the Length of Bile Loop Determines Serum Bile Acid Concentration and Glycemic Control After Bariatric Surgery

Contact Info

Product

Resources

About