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Targeting Islets: Metabolic Surgery Is More than a Bariatric Surgery

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Abstract

Metabolic surgery is an effective therapy for diabetic patients with obesity. The main mechanisms underlying the effects of metabolic surgery include food intake restriction and the accompanying reduced daily caloric intake and changes in gut hormones and bile acid. Insulin resistance and impaired β-cell function contribute to the development of type 2 diabetes. An increasing number of studies have focused on the central role of islet function in type 2 diabetes. In this article, we review the related high-quality literature and summarize the following mechanisms and principles underlying metabolic surgery in the context of islet function protection: (1) reduced glucotoxicity and chronic inflammation help facilitate better β-cell function and the preservation of β-cell mass following metabolic surgery; (2) based on the increased levels of GLP-1 and PYY after metabolic surgery, gut hormones appear to play a significant role in improving β-cell function through the GLP-1R signaling pathways; (3) the bile acid signaling pathway could affect β-cell function; and (4) the GLP-1R and bile acid signaling pathways could also cause other endocrine cells to contribute to islet function.

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Abbreviations

IDF:

International Diabetes Federation

T2D:

Type 2 diabetes

RYGB:

Roux-en-Y gastric bypass

SG:

Sleeve gastrostomy

BA:

Bile acid

GPCRs:

G protein-coupled receptors

PKC:

Protein kinase C

PKA:

Protein kinase A

IRS-2:

Insulin receptor substrate-2

PKB:

Protein kinase B

TGF-β:

Transforming growth factor-β

FFA:

Free fatty acid

GLP-1:

Glucagon-like peptide 1

PYY:

Peptide-YY

GIP:

Gastric inhibitory polypeptide

FXR:

Farnesoid X receptor

TGR5:

G protein-coupled bile acid receptor 5

AUC:

Area under the curve

FGF-19:

Fibroblast growth factor-19

GLP-1R:

GLP-1 receptor

IL-1β:

Interleukin-1β

NF-κB:

Nuclear factor-κB

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Acknowledgements

This study was supported by the National Key R&D Program of China (2016YFC1305000, 2016YFC1305001), the National Science and Technology Infrastructure Program (2015BAI12B13), the National Natural Science Foundation of China (81770775, 91749118, 81370017, 81130015, and 81000316), the Planned Science and Technology Project of Hunan Province (2017RS3015) and Natural Science Foundation of Hunan Province, China (14JJ3034), and the National Basic Research Program of China (2014CB910500).

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  1. Xi Chen and Jingjing Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Metabolism and Endocrinology, The Second Xiangya Hospital and Diabetes Center, Institute of Metabolism and Endocrinology and National Clinical Research Center for Metabolic Diseases, Central South University, Changsha, 410011, Hunan, China

    Xi Chen, Jingjing Zhang & Zhiguang Zhou

  2. Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education; National Clinical Research Center for Metabolic Diseases; Metabolic Syndrome Research Center, the Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China

    Xi Chen, Jingjing Zhang & Zhiguang Zhou

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  1. Xi Chen
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Correspondence to Zhiguang Zhou.

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Chen, X., Zhang, J. & Zhou, Z. Targeting Islets: Metabolic Surgery Is More than a Bariatric Surgery. OBES SURG 29, 3001–3009 (2019). https://doi.org/10.1007/s11695-019-03979-1

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