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Glycemic effect of pancreatic preproglucagon in mouse sleeve gastrectomy.

ABSTRACT: Intestinally derived glucagon-like peptide-1 (GLP-1), encoded by the preproglucagon (Gcg) gene, is believed to function as an incretin. However, our previous work questioned this dogma and demonstrated that pancreatic peptides rather than intestinal Gcg peptides, including GLP-1, are a primary regulator of glucose homeostasis in normal mice. The objective of these experiments was to determine whether changes in nutrition or alteration of gut hormone secretion by bariatric surgery would result in a larger role for intestinal GLP-1 in the regulation of insulin secretion and glucose homeostasis. Multiple transgenic models, including mouse models with intestine- or pancreas tissue-specific Gcg expression and a whole-body Gcg-null mouse model, were generated to study the role of organ-specific GLP-1 production on glucose homeostasis under dietary-induced obesity and after weight loss from bariatric surgery (vertical sleeve gastrectomy; VSG). Our findings indicated that the intestine is a major source of circulating GLP-1 after various nutrient and surgical stimuli. However, even with the 4-fold increase in intestinally derived GLP-1 with VSG, it is pancreatic peptides, not intestinal Gcg peptides, that are necessary for surgery-induced improvements in glucose homeostasis.

SUBMITTER: Kim KS

PROVIDER: S-EPMC6824314 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Glycemic effect of pancreatic preproglucagon in mouse sleeve gastrectomy.

Kim Ki-Suk KS Hutch Chelsea R CR Wood Landon L Magrisso Irwin J IJ Seeley Randy J RJ Sandoval Darleen A DA

JCI insight 20191017 20

Intestinally derived glucagon-like peptide-1 (GLP-1), encoded by the preproglucagon (Gcg) gene, is believed to function as an incretin. However, our previous work questioned this dogma and demonstrated that pancreatic peptides rather than intestinal Gcg peptides, including GLP-1, are a primary regulator of glucose homeostasis in normal mice. The objective of these experiments was to determine whether changes in nutrition or alteration of gut hormone secretion by bariatric surgery would result in ...[more]

PMID: 31619587

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Project description:BACKGROUND:Laparoscopic sleeve gastrectomy (LSG) modifies the upper gastrointestinal tract motility. Controversial data currently exist. The aim of the study was to evaluate esophageal motility before and after LSG. PATIENTS AND METHODS:Morbid obese patients scheduled for LSG underwent reflux symptoms evaluation and manometry preoperatively and postoperatively. The preoperative and postoperative results were compared and analyzed. RESULTS:Eighteen patients were enrolled. Heartburn and regurgitation improved in 38.9% and 11.1% of the patients, but deteriorated in 11.1% and 27.8% of the patients, respectively. Lower esophageal sphincter (LES) total length decreased postoperatively (p=0.002). Resting and residual pressures tended to decrease postoperatively (mean difference [95% confidence interval]: -4 [-8.3/0.2] mmHg, p=0.060; -1.4 [-3/0.1] mmHg, p=0.071, respectively). Amplitude pressure decreased from 95.7±37.3 to 69.8±26.3 mmHg at the upper border of LES (p=0.014), and tended to decrease at the distal esophagus from 128.5±30.1 to 112.1±35.4 mmHg (p=0.06) and mid-esophagus from 72.7±34.5 to 49.4±16.7 mmHg (p=0.006). Peristaltic normal swallow percentage increased from 47.2±36.8 to 82.8±28% (p=0.003). Postoperative regurgitation was strongly negatively correlated with LES total length (Spearman's r=-0.670). When groups were compared according to heartburn status, statistical significance was observed between the groups of improvement and deterioration regarding postoperative residual pressure and postoperative relaxation (p<0.002, p<0.002, respectively). With regard to regurgitation status, there was statistically significant difference between groups regarding preoperative amplitude pressure at the upper border of LES (p<0.056). CONCLUSION:Patients developed decreased LES length and weakened LES pressure after LSG. Esophageal body peristalsis was also affected in terms of decreased amplitude pressure, especially at the upper border of LES. Nevertheless, body peristalsis was normalized postoperatively. LSG might not deteriorate heartburn. Regurgitation might increase following LSG due to shortening of LES length, particularly in patients with range of preoperative amplitude pressure at the upper border of LES of 38.9-92.6 mmHg.

Dataset Information

Glycemic effect of pancreatic preproglucagon in mouse sleeve gastrectomy.

Publications

Glycemic effect of pancreatic preproglucagon in mouse sleeve gastrectomy.

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