Bile acids drive colonic secretion of glucagon-like-peptide 1 and peptide-YY in rodents

Abstract

A large number of glucagon-like-peptide-1 (GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo, we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3.5- and 2.9-fold, respectively. Furthermore, we find that responses depend on BA absorption followed by basolateral activation of the BA-receptor Takeda-G protein-coupled-receptor 5. Surprisingly, the apical sodium-dependent BA transporter, which serves to absorb conjugated BAs, was not required for colonic conjugated BA absorption or conjugated BA-induced peptide secretion. In conclusion, we demonstrate that BAs represent a major physiological stimulus for colonic L-cell secretion. NEW & NOTEWORTHY By the use of isolated perfused rodent colon preparations we show that bile acids are potent and direct promoters of colonic glucagon-like-peptide 1 and peptide-YY secretion. The study provides convincing evidence that basolateral Takeda-G protein-coupled-receptor 5 activation is mediating the effects of bile acids in the colon and thus add to the existing literature described for L cells in the ileum.

Dumping syndrome after bariatric surgery

“…excess weight loss of 60%). Both pati ents Figure 4: Roux-en-Y gastric bypass 42 Figure 5: Mini gastric bypass 43 and doctors refused to take the more risky second step of this procedure, and the vertical sleeve gastrectomy became a stand alone (restrictive) procedure. 18 In the early years of bariatric surgery, it was believed that operations could be divided into restrictive (jaw wiring, banding, sleeve gastrectomy) and malabsortive procedures (RYGB, Scopinaro, duodenal switch), as stated above.…”

“…not provoked by a meal). 41,42 A fast of up to 72 hours (usually 48 hours) in a supervised hospital setting to assess hypoglycemia and the pathological lack of decrease in insulin secretion may be indicated in case of doubt. 39,41 Surreptitious use of glucose-lowering medications (e.g.…”

“…79 Both short-and long-acting formulations of somatostatin analogues have demonstrated efficacy by slowing gastric emptying, improving hypoglycemia, and reducing early and late dumping symptoms (Table 4). 15,66,[80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95] Somatostatin analogues may be administered subcutaneously three times daily as a shortacting formulation or intramuscularly once every 2 to 4 weeks as a long-acting formulation. Short-acting formulations may be more effective at improving some dumping symptoms such as hypoglycemia 15,82,83,85 ; however, the need for repeated injections throughout the day is often a major limitation to the long-term administration of short-acting formulations.…”

“…96,97 Furthermore, during both short-treatment and long-term treatment, a proportion of patients with dumping syndrome do not respond to currently available somatostatin analogues. 1,15,[87][88][89] Somatostatin analogues have not received regulatory approval for the treatment of dumping syndrome.…”

“…31 Roslin et al performed two studies on abnormal glucose tolerance testing in 2011 and 2013; the second probably being an extension of the first study. 16,42 They concluded that abnormal oGTT results are a common finding after gastric bypass surgery because 68-72% of the patients had reactive hypoglycaemia defined as < 3.3 mmol/l (60 mg/dl). No control group was used.…”