Background: It has been hypothesized that glucagon-like peptide-1 (GLP-1), secreted by ileal L cells, plays a key-role in the resolution of type 2 diabetes after bariatric operations whose common feature is an expedite nutrient delivery to the hindgut. Ileal transposition (IT), an operation that permits L-cell stimulation by undigested food, was employed to verify this theory. Methods: IT was carried out in Goto-Kakizaki (GK) type 2 diabetic rats and in euglycemic Sprague-Dawley (SD) rats. Glucose tolerance, insulin resistance, food-intake, body weight, pancreas morphology, and function were evaluated to track the effects of IT on diabetes. Intact GLP-1 secretion and gene expression pattern of the transposed ileum were investigated to verify the molecular bases of the hindgut action. Results: In GK rats, IT significantly improved glucose tolerance, insulin sensitivity, and acute insulin response without affecting body weight and food intake. Immunohistochemistry revealed remodeled islets strictly resembling that of euglycemic rats and signs of -cell neogenesis starting with exocrine structures. GLP-1 secretion in GK transposed rats was characterized by a more sustained response to oral glucose compared with nontreated rats. Gene expression of Proglucagon, Proconvertase 1/3 (PC1/ 3), and Chromogranin A in the transposed ileum significantly enhanced. Effects on glucose metabolism and pancreas morphology were not observed in the euglycemic rats as a consequence of the glucosedependent action of GLP-1. Conclusions: This study gives strong evidences for the crucial role of the hindgut in the resolution of diabetes after Roux-en-Y gastric bypass (GBP) and biliopancreatic diversion (BPD). Moreover, these findings confirm at the preclinical level that IT is a surgical procedure of possible relevance in the therapy of type 2 diabetes in non–overweight and mildly obese patients. (Surgery 2007;142:74-85.)
How the Hindgut can cure Type 2 diabetes. Ileal transposition improves glucose metabolism and beta-cell function in Goto-Kakizaki rats through an enhanced gene expression of GLP-1 and L-cell number
PATRITI, Alberto;AISA, Maria Cristina;SIDONI, Angelo;GALLI, Francesco;GULLA', Nino;DONINI, Annibale
2007
Abstract
Background: It has been hypothesized that glucagon-like peptide-1 (GLP-1), secreted by ileal L cells, plays a key-role in the resolution of type 2 diabetes after bariatric operations whose common feature is an expedite nutrient delivery to the hindgut. Ileal transposition (IT), an operation that permits L-cell stimulation by undigested food, was employed to verify this theory. Methods: IT was carried out in Goto-Kakizaki (GK) type 2 diabetic rats and in euglycemic Sprague-Dawley (SD) rats. Glucose tolerance, insulin resistance, food-intake, body weight, pancreas morphology, and function were evaluated to track the effects of IT on diabetes. Intact GLP-1 secretion and gene expression pattern of the transposed ileum were investigated to verify the molecular bases of the hindgut action. Results: In GK rats, IT significantly improved glucose tolerance, insulin sensitivity, and acute insulin response without affecting body weight and food intake. Immunohistochemistry revealed remodeled islets strictly resembling that of euglycemic rats and signs of -cell neogenesis starting with exocrine structures. GLP-1 secretion in GK transposed rats was characterized by a more sustained response to oral glucose compared with nontreated rats. Gene expression of Proglucagon, Proconvertase 1/3 (PC1/ 3), and Chromogranin A in the transposed ileum significantly enhanced. Effects on glucose metabolism and pancreas morphology were not observed in the euglycemic rats as a consequence of the glucosedependent action of GLP-1. Conclusions: This study gives strong evidences for the crucial role of the hindgut in the resolution of diabetes after Roux-en-Y gastric bypass (GBP) and biliopancreatic diversion (BPD). Moreover, these findings confirm at the preclinical level that IT is a surgical procedure of possible relevance in the therapy of type 2 diabetes in non–overweight and mildly obese patients. (Surgery 2007;142:74-85.)I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
