Duodeno-jejunal bypass restores β-cell hypersecretion and islet hypertrophy in western diet obese rats

• Published in: Endocrine 2018-06, Vol.60 (3), p.407-414
• Main Authors: Mendes, Mariana Carla, Bonfleur, Maria Lúcia, Ribeiro, Rosane Aparecida, Lubaczeuski, Camila, Fêo, Ana Flavia Justino, Vargas, Rodrigo, Carneiro, Everardo Magalhães, Boschero, Antonio Carlos, Araujo, Allan Cezar Faria, Balbo, Sandra Lucinei
• Format: Article
• Language: English
• Subjects: Acetic acid; Acetylcholine receptors (muscarinic); Adipose tissue; AKT protein; Animals; Blood glucose; Blood Glucose - metabolism; Body weight; Body Weight - physiology; Body weight loss; Carbachol; Cyclic AMP; Cytology; Diabetes; Diet; Diet, Western; Endocrine Surgery; Endocrinology; Fasting; Forskolin; Gastric Bypass - methods; Glucose; Glucose Tolerance Test; Homeostasis; Humanities and Social Sciences; Hypertrophy; Insulin; Insulin Resistance; Insulin-Secreting Cells - metabolism; Internal Medicine; Islets of Langerhans; Islets of Langerhans - metabolism; Kinases; Male; Medicine; Medicine & Public Health; multidisciplinary; Obesity; Obesity - metabolism; Obesity - surgery; Pancreas; Phorbol 12-myristate 13-acetate; Protein kinase; Proteins; Rats; Rats, Wistar; Rodents; Science; Skeletal muscle; Surgery; Syntaxin; Syntaxin 1
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-018-1578-4

Purpose Duodeno-jejunal bypass (DJB) operation improves glucose homeostasis in morbid obesity, independently of weight loss or reductions in adiposity, through mechanisms not yet fully elucidated. Herein, we evaluated the effects of DJB upon glucose homeostasis, endocrine pancreatic morphology, and β-cell responsiveness to potentiating agents of cholinergic and cAMP pathways, in western diet (WD) obese rats, at 2 months after operation. Methods From 8 to 18 weeks of age male Wistar rats fed on a WD. After this period, a sham (WD Sham group) or DJB (WD DJB) operations were performed. At 2 months after operation glucose homeostasis was verified. Results Body weight was similar between WD DJB and WD Sham rats, but WD DJB rats showed a decrease in Lee index, retroperitoneal and perigonadal fat pads. Also, WD DJB rats displayed reduced fasting glycemia and insulinemia, and increased insulin-induced Akt activation in the gastrocnemius. Islets from WD DJB rats secreted less amounts of insulin, in response to activators of the cholinergic (carbachol and phorbol 12-myristate 13-acetate) and cAMP (forskolin and 3-isobutyl-1-methyl-xantine) pathways. Islets of WD DJB rats had higher sintaxin-1 protein content than WD Sham, but without modification in muscarinic-3 receptor, protein kinase (PK)-Cα, and (PK)-Aα protein amounts. In addition, islets of WD DJB animals showed reduction in islets and β-cell masses. Conclusion DJB surgery improves fasting glycemia and insulin action in skeletal muscle. Better endocrine pancreatic morphofunction was associated, at least in part, with the regulation of the cholinergic and cAMP pathways, and improvements in syntaxin-1 islet protein content induced by DJB.