-We-evaluated-nave-fasting-serum-GLP1-and-GLP2-levels-in-METHODS-Fiftyfive-IF-patients-with-median-age-4-IQR-112-years-and-47-matched-healthy-controls-underwent-measurement-of-fasting-serum-GLP1-and-GLP2-p

RESULTS: Serum GLP-2 [19 (13-27) vs 11 (7-18) ng/mL, P < 001], but not GLP-1 [6 (4-15) vs 6 (3-10) ng/mL, P = 076], levels were increased in IF patients. Serum GLP-2 concentrations were higher in patients with small bowel-colic continuity [21 (15-30) ng/mL] compared to patients with an endostomy [10 (6-17) ng/mL, P = 028], whereas no association with preservation of ileum or ileocecal valve was observed. During PN delivery, GLP-2 inversely associated with remaining small bowel length (r = -000, P = 041) and frequency of PN infusions (r = -049, P = 042). Serum GLP-1 levels were lower in patients receiving PN currently [4 (2-5)] compared to patients, who had weaned off PN [6 (5-21), P = 005], and correlated positively with duration of PN (r = 063, P = 002) and negatively with percentage parenteral energy requirement (r = -016, P = 006).CONCLUSIONS: In pediatric IF, serum GLP-2 levels increase in patients with small bowel-colic continuity proportionally to the length of resected small intestine. Pancreatic hormones and other blood sugar regulating drugs in serum GLP-1 and GLP-2 levels paralleled reducing requirement for parenteral support.

These findings support regulation of intestinal adaption by A GLP-1/GLP-2 receptor dual agonist to treat NASH: Targeting the gut-liver axis Yonsei University College of Medicine, Seoul, Korea.Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea.University College of Medicine, Seoul, Korea.BACKGROUND AND AIMS: Currently there is no Food and Drug Administration-approved drug to treat NAFLD and NASH, the rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut-liver axis in their pathogenesis, we investigated the therapeutic effect of a long-acting dual agonist of glucagon-like peptide (GLP)-1 and GLP-2 receptors in mice with NAFLD/NASH.APPROACH AND RESULTS: C57BL/6J mice were fed a choline-deficient high-fat diet/high fructose and sucrose solution.

After 16 weeks, mice were randomly allocated to receive vehicle, GLP1-Fc, GLP2-Fc, or GLP1/2-Fc fusion (GLP1/2-Fc) subcutaneously every 2 days for 4 weeks. Body weight was monitored, insulin/glucose tolerance tests were performed, feces were collected, and microbiome profiles were analyzed. Immobilized cell systems were used to evaluate direct peptide effect. Immunohistochemistry, quantitative PCR, immunoblot analysis, tunnel assay, and biochemical assays were performed to assess drug effects on inflammation, hepatic fibrosis, cell death, and intestinal structures. The mice had well-developed NASH phenotypes. GLP1/2-Fc reduced body weight, glucose levels, hepatic triglyceride levels, and cellular apoptosis. It improved liver fibrosis, insulin sensitivity, and intestinal tight junctions, and increased microvillus height, crypt depth, and goblet cells of intestine compared with a vehicle group.

Similar effects of GLP1/2-Fc were found in in vitro cell systems. GLP1/2-Fc also changed microbiome profiles. We applied fecal microbiota transplantation (FMT) gain further insight into the mechanism of GLP1/2-Fc-mediated protection. We confirmed that FMT exerted an additive effect on GLP1-Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation, and hepatic fibrosis.CONCLUSIONS: A long-acting dual agonist of GLP-1 and GLP-2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.10760/cma.j.

cn441530-20220712-00305.[Effects of metabolic surgery on islet function in Asian patients with type 2 [Article in Chinese; Abstract available in Chinese from the publisher]Central South University, Changsha 410013, China.Type 2 diabetes is a high-profile global public health problem, particularly in Asia. The young age of onset, low body mass index, and early appearance of pancreatic islet dysfunction are characteristics of Asian patients with T2DM. glipizide side effects has become the standard treatment for T2DM patients and can significantly improve T2DM through a variety of mechanisms including modulation of energy homeostasis and reduction of body fat mass. Indeed, restoration of islet function also plays an integral role in the remission of T2DM. After metabolic surgery, islet function in Asian T2DM patients has improved significantly, with proven short-term and long-term effects.

In addition, islet function is an important criterion and reference for patient selection prior to metabolic surgery. The mechanism of islet function improvement after metabolic surgery is not clear, but postoperative anatomical changes in the gastrointestinal tract leading to a number of hormonal changes seem to be the potential cause, including glucagon-like peptide-1, gastric inhibitory polypeptide, peptide YY, ghrelin, and cholecystokinin.