RT Journal Article SR Electronic T1 Restoration of Euglycemia After Duodenal Bypass Surgery Is Reliant on Central and Peripheral Inputs in Zucker fa/fa Rats JF Diabetes JO Diabetes FD American Diabetes Association SP 1074 OP 1083 DO 10.2337/db12-0681 VO 62 IS 4 A1 Jiao, Jian A1 Bae, Eun Ju A1 Bandyopadhyay, Gautam A1 Oliver, Jason A1 Marathe, Chaitra A1 Chen, Michael A1 Hsu, Jer-Yuan A1 Chen, Yu A1 Tian, Hui A1 Olefsky, Jerrold M. A1 Saberi, Maziyar YR 2013 UL http://diabetes.diabetesjournals.org/content/62/4/1074.abstract AB Gastrointestinal bypass surgeries that result in rerouting and subsequent exclusion of nutrients from the duodenum appear to rapidly alleviate hyperglycemia and hyperinsulinemia independent of weight loss. While the mechanism(s) responsible for normalization of glucose homeostasis remains to be fully elucidated, this rapid normalization coupled with the well-known effects of vagal inputs into glucose homeostasis suggests a neurohormonally mediated mechanism. Our results show that duodenal bypass surgery on obese, insulin-resistant Zucker fa/fa rats restored insulin sensitivity in both liver and peripheral tissues independent of body weight. Restoration of normoglycemia was attributable to an enhancement in key insulin-signaling molecules, including insulin receptor substrate-2, and substrate metabolism through a multifaceted mechanism involving activation of AMP-activated protein kinase and downregulation of key regulatory genes involved in both lipid and glucose metabolism. Importantly, while central nervous system–derived vagal nerves were not essential for restoration of insulin sensitivity, rapid normalization in hepatic gluconeogenic capacity and basal hepatic glucose production required intact vagal innervation. Lastly, duodenal bypass surgery selectively altered the tissue concentration of intestinally derived glucoregulatory hormone peptides in a segment-specific manner. The present data highlight and support the significance of vagal inputs and intestinal hormone peptides toward normalization of glucose and lipid homeostasis after duodenal bypass surgery.