Relief of diabetes by duodenal-jejunal bypass sleeve implantation in the high-fat diet and streptozotocin-induced diabetic rat model is associated with an increase in GLP-1 levels and the number of GLP-1-positive cells

Abstract

A recently invented duodenal-jejunal bypass sleeve (DJBS) implanted in the duodenum and proximal jejunum has exhibited good glycemic control in diabetes mellitus. However, the specific mechanism by which DJBS placement induces the remission of diabetes is not well known. Previous studies have indicated that changes in the pattern of gut hormone secretion may play a role. The aim of the present study was to explore the role of intestinal L cells and the production of glucagon-like peptide-1 (GLP-1) by these cells in DJBS implantation-induced glycemic control in diabetic rats. A DJBS was placed in the proximal small intestine of rats with diabetes induced by a high-fat diet and low-dose streptozotocin (STZ), and the effects of the DJBS on the remission of diabetes and the GLP-1 levels of plasma and intestinal tissues were investigated 12 weeks after DJBS placement. The number of intestinal GLP-1 positive cells was also counted. When the DJBS had been in place for 12 weeks, the plasma glucose level of the DJBS-implanted rats decreased significantly from 23.33±1.56 mmol/l prior to surgery to 7.70±0.84 mmol/l and the diabetes mellitus was relieved completely; however, diabetic control rats and diabetic rats subjected to sham surgery did not show any improvement. Parallel with the remission of diabetes, the plasma and distal ileum GLP-1 levels of rats in the DJBS implantation group were also higher than those of rats in the diabetic control and sham surgery groups. The number of GLP-1-positive cells in the distal ileum was also higher in the DJBS implantation group than in the diabetic control and sham surgery groups (31.0±2.6 vs. 23.5±4.4 vs. 23.0±3.2 respectively; P<0.01). DJBS implantation effectively led to the remission of diabetes in rats with diabetes induced by a high-fat diet and low-dose STZ when implanted for 12 weeks. The remission of diabetes may be associated with the increase in the number of L cells and elevation of GLP-1 levels induced by DJBS implantation.

“Dysfunctions” induced by Roux-en-Y gastric bypass surgery are concomitant with metabolic improvement independent of weight loss

“…Because of greatly reduced beta cell number and presumably decreased insulin levels, body weights of STZ rats did not increase throughout the experiment. Weight gain of STZ rats after RYGB was consistent with results of previous studies 25 and reflects amelioration of diabetes. The mechanism of weight gain in STZ rats undergoing RYGB may be due to increased pancreatic beta cell area 26 , reduced beta cell apoptosis 27 , increased beta cell proliferation 28 , and/or improved beta cell function 29 , as documented previously in rodents undergoing RYGB.…”

Distribution and hormonal characterization of primary murine L cells throughout the gastrointestinal tract

“…Recent investigations have shown that the increased plasma GLP‐1 concentration in patients with type 2 diabetes who underwent a gastric bypass or sleeve gastrectomy surgery normalized their blood glucose levels. It has been reported that the possible mechanisms are that these surgeries lead to gut hypertrophy and an increase in the number of L cells in the LI, resulting in increased plasma GLP‐1 levels. However, these kinds of surgery are greatly invasive and expensive.…”

Effects of Bariatric Endoscopy on Non-Alcoholic Fatty Liver Disease: A Comprehensive Systematic Review and Meta-Analysis

“…It has been reported that IGB therapy reduced plasma ghrelin levels (54) and increased levels of sirtuin-1 (55) (a well-known regulator of energy homeostasis and metabolism). Following DJBL implantation, increased fasting and postprandial glucagon-like peptide-1 (GLP-1) levels have been observed (34,56). GLP-1 can stimulate glucose-dependent insulin secretion, thereby reducing postprandial hyperglycemia.…”