glucagon-like-peptide-2 and Hypertrophy

PURPOSE : Intestinal remodeling and adaptation of the alimentary limb after Roux-en-Y gastric bypass (RYGB) play an important role in the pathophysiological events that lead to type 2 diabetes mellitus (T2DM) improvement. Intestinal absorptive loop hypertrophy and growth following surgery have been related to GLP-2 secretion by ileal L-cells. The secretion of peptide tyrosine-tyrosine (PYY) enterohormone after a meal has been proposed as a trigger for ileal secretion of GLP-1. Our aim is to determine the role of PYY as a GLP-2 secretion modulator as an adaptation result in the alimentary limb after RYGB.. We used a non-obese euglycemic rodent model. Circulating glucose, insulin, PYY, and GLP-2 were measured in the experimental and control groups. We used four groups: fasting control, Sham-operated, RYGB-operated (RYGB), and RYGB-operated and treated with BIIE0246 (RYGB + BII). BIIE0246 is a NPY2 receptor antagonist in L-cells. Intestinal glucose transporters and GLP-1 and PYY gut expression and hypertrophy were analyzed after 12 weeks of surgery.. RYGB increased PYY3-36 plasma levels in rats with or without BII treatment. A high-insulin response was observed in the RYGB group but not in the control or RYGB + BII groups. BIIE0246 treatment limited plasma GLP-2 levels. In the alimentary intestinal limb, hypertrophy and SGLT1 and GLUT1 expression appeared to be reduced after RYGB compared to controls.. The postprandial ileal PYY secretion is enhanced after RYGB. This increase mediates GLP-2 release through its binding to the Y2 receptor on L-cells. This mechanism plays a role in alimentary limb hypertrophy after surgery.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Gastric Bypass; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose; Hypertrophy; Insulins; Obesity, Morbid; Rats

Factors leading to weight loss and weight stabilization after bariatric surgery are not fully understood. The aims of this study were to develop an animal model for biliopancreatic diversion (BPD) and to determine changes in gut hormones, malabsorption and small bowel histology postoperatively.. 2 groups of Wistar rats underwent sham and BPD surgery. Daily postoperative weights and food intake were measured. 24-hour fecal collections were performed at Day 6 and 21. Bomb calorimetry was performed to determine the fecal calorific values. At day 23, levels of peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2) were determined and small bowel biopsies were taken.. Animals in the BPD group had significant reduction in weight (P<0.001) and in food intake (P<0.001) compared to the sham group. Serum levels of PYY, GLP-1 and GLP-2 in the BPD group were significantly higher (P<0.005). Animals in the BPD group had significantly higher fecal energy content at Day 6 (P<0.001) but not at Day 21 when compared to the sham group. Small bowel histology confirmed the presence of significantly increased mitosis (P=0.03) and labelled cells (P=0.002) in the BPD animals when compared to sham.. In our animal model, the higher levels of PYY, GLP-1 and GLP-2 after BPD may be due to gut adaptation and hypertrophy and could be important in inducing and maintaining weight loss after bariatric surgery.

Topics: Animals; Biliopancreatic Diversion; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Hypertrophy; Intestines; Male; Peptide YY; Rats; Rats, Wistar