Sleeve Gastrectomy Suppresses Hepatic Glucose Production and Increases Hepatic Insulin Clearance Independent of Weight Loss

Rachel Ben Haroush Schyr*, Abbas Al-Kurd, Botros Moalem, Anna Permyakova, Hadar Israeli, Aya Bardugo, Yhara Arad, Liron Hefetz, Michael Bergel, Arnon Haran, Shahar Azar, Itia Magenheim, Joseph Tam, Ronit Grinbaum, Danny Ben-Zvi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Bariatric operations induce weight loss, which is associated with an improvement in hepatic steatosis and a reduction in hepatic glucose production. It is not clear whether these outcomes are entirely due to weight loss, or whether the new anatomy imposed by the surgery contributes to the improvement in the metabolic function of the liver. We performed vertical sleeve gastrectomy (VSG) on obese mice provided with a high-fat high-sucrose diet and compared them to diet and weight-matched sham-operated mice (WMS). At 40 days after surgery, VSG-operated mice displayed less hepatic steatosis compared with WMS. By measuring the fasting glucose and insulin levels in the blood vessels feeding and draining the liver, we showed directly that hepatic glucose production was suppressed after VSG. Insulin levels were elevated in the portal vein, and hepatic insulin clearance was elevated in VSG-operated mice. The hepatic expression of genes associated with insulin clearance was upregulated. We repeated the experiment in lean mice and observed that portal insulin and glucagon are elevated, but only insulin clearance is increased in VSG-operated mice. In conclusion, direct measurement of glucose and insulin in the blood entering and leaving the liver shows that VSG affects glucose and insulin metabolism through mechanisms independent of weight loss and diet.

Original languageAmerican English
Pages (from-to)2289-2298
Number of pages10
JournalDiabetes
Volume70
Issue number10
DOIs
StatePublished - Oct 2021

Bibliographical note

Publisher Copyright:
© 2021 by the American Diabetes Association.

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