Published online Oct 21, 2023. doi: 10.3748/wjg.v29.i39.5471
Peer-review started: July 14, 2023
First decision: September 6, 2023
Revised: September 11, 2023
Accepted: October 11, 2023
Article in press: October 11, 2023
Published online: October 21, 2023
Processing time: 91 Days and 13.4 Hours
The small intestine is known to play a crucial role in the development and remission of diabetes mellitus (DM). However, the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in diabetic rats is not fully understood.
To elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism.
Streptozotocin (STZ) was used to induce DM in Sprague-Dawley (SD) rats at a dose of 60 mg/kg. The rats were then randomly divided into two groups: The mid-small intestine bypass (MSIB) group and the sham group (underwent switch laparotomy). Following a 6-wk recovery period post-surgery, the rats underwent various assessments, including metabolic parameter testing, analysis of liver glycogen levels, measurement of key gluconeogenic enzyme activity, characterization of the gut microbiota composition, evaluation of hormone levels, determination of bile acid concentrations, and assessment of the expression of the intestinal receptors Takeda G protein-coupled receptor 5 and farnesoid X receptor.
The MSIB group of rats demonstrated improved glucose metabolism and lipid metabolism, along with increased hepatic glycogen content. Furthermore, there was a decrease in the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase. Importantly, the MSIB group exhibited a substantial increase in the abundances of intestinal Lactobacillus, Clostridium symbiosum, Ruminococcus gnavus, and Bilophila. Moreover, higher levels of secondary bile acids, such as intestinal lithocholic acid, were observed in this group. Remarkably, the changes in the gut microbiota showed a significant correlation with the expression of key gluconeogenic enzymes and glucagon-like peptide 1 (GLP-1) at 6 wk postoperatively, highlighting their potential role in glucose regulation. These findings highlight the beneficial effects of mid-small intestine bypass on glucose metabolism and the associated modulation of the gut microbiota.
The findings of this study demonstrate that the introduction of postoperative intestinal Clostridium symbiosum in the mid-small intestine contributes to the enhancement of glucose metabolism in nonobese diabetic rats. This improvement is attributed to the increased inhibition of hepatic gluconeogenesis mediated by GLP-1, resulting in a favorable modulation of glucose homeostasis.
Core Tip: Intestinal function plays a pivotal role in the onset, progression, and alleviation of diabetes. However, research on surgical procedures and functions involving the mid-small intestine is limited. The precise mechanisms by which the mid-small intestine improves glucose metabolism in diabetic rats remain largely unclear. This study explores the effects of mid-small intestine bypass surgery on diabetic rats. Post-surgery, there was an increase in the abundance of Clostridium symbiosum in the rat gut, which contributed to improved glucose metabolism through the inhibition of hepatic gluconeogenesis mediated by glucagon-like peptide 1. These findings provide a theoretical basis for non-surgical interventions in the treatment of metabolic disorders associated with diabetes.