Intact neural system of the portal vein is important for maintaining normal glucose metabolism by regulating glucagon-like peptide-1 and insulin sensitivity

• Portal denervation leads to increased GLP-1.
• Portal denervation causes decreased insulin sensitivity.
• Portal denervation induces increased blood glucose levels.
• Portal denervation does not affect food intake.

The portal neural system may have an important role on the regulation of glucose homeostasis since activation of the gut–brain–liver neurocircuit by nutrient sensing in the proximal intestine reduces hepatic glucose production through enhanced liver insulin sensitivity. Although there have been many studies investigating the role of portal neural system, surgical denervation of the sole portal vein has not been reported to date. The aim of this study was to clarify the role of the portal neural system on the regulation of glucose homeostasis and food intake in the physiological condition. Surgical denervation of portal vein (DV) was performed in 10 male 12 week-old Wistar rats. The control was a sham operation (SO). One week after surgery, food intake and body weight were monitored; an oral glucose tolerance test (OGTT) was performed; and glucagon-like peptide-1 (GLP-1) and insulin levels during OGTT were assayed. In addition, insulinogenic index, homeostatic model assessment, and Matsuda index were calculated. All rats regained the preoperative body weight at one week after surgery. There was no significant difference in food intake between DV and SO rats. DV rats exhibited increased blood glucose levels associated with decreased insulin sensitivity but increased GLP-1 and insulin secretion during OGTT. In summary, in the physiological state, loss of the portal neural system leads to decreased insulin sensitivity and increased blood glucose levels but does not affect food intake. These data indicate that an intact portal neural system is important for maintaining normal glucose metabolism.