Glycerate from intestinal fructose metabolism induces islet cell damage and glucose intolerance

Yanru Wu; Chi Wut Wong; Eric N Chiles; Allyson L Mellinger; Hosung Bae; Sunhee Jung; Ted Peterson; Jamie Wang; Marcos Negrete; Qiang Huang; Lihua Wang; Cholsoon Jang; David C Muddiman; Xiaoyang Su; Ian Williamson; Xiling Shen

doi:10.1016/j.cmet.2022.05.007

Glycerate from intestinal fructose metabolism induces islet cell damage and glucose intolerance

Cell Metab. 2022 Jul 5;34(7):1042-1053.e6. doi: 10.1016/j.cmet.2022.05.007. Epub 2022 Jun 9.

Authors

Yanru Wu¹, Chi Wut Wong², Eric N Chiles³, Allyson L Mellinger⁴, Hosung Bae⁵, Sunhee Jung⁵, Ted Peterson⁶, Jamie Wang⁶, Marcos Negrete⁶, Qiang Huang⁷, Lihua Wang⁶, Cholsoon Jang⁵, David C Muddiman⁸, Xiaoyang Su⁹, Ian Williamson¹⁰, Xiling Shen¹¹

Affiliations

¹ Department of Prosthodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, China; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA.
² Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA; Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
³ Metabolomics Shared Resource, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ 08903, USA.
⁴ FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA.
⁵ Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
⁶ Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA.
⁷ Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA; Department of Pediatric Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
⁸ FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA; Molecular Education, Technology and Research Innovation Center, North Carolina State University, Raleigh, NC 27695, USA.
⁹ Metabolomics Shared Resource, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ 08903, USA; Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA.
¹⁰ Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA; Gastroenterology Division, Department of Medicine, Duke University, Durham, NC 27710, USA. Electronic address: ian.williamson@duke.edu.
¹¹ Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, USA. Electronic address: xiling.shen@duke.edu.

Abstract

Dietary fructose, especially in the context of a high-fat western diet, has been linked to type 2 diabetes. Although the effect of fructose on liver metabolism has been extensively studied, a significant portion of the fructose is first metabolized in the small intestine. Here, we report that dietary fat enhances intestinal fructose metabolism, which releases glycerate into the blood. Chronic high systemic glycerate levels induce glucose intolerance by slowly damaging pancreatic islet cells and reducing islet sizes. Our findings provide a link between dietary fructose and diabetes that is modulated by dietary fat.

Keywords: diabetes; dietary fat; fructose; glucose intolerance; glycerate; insulin; intestine; islet cell; metabolism; western diet.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Blood Glucose
Diabetes Mellitus, Type 2*
Diet, High-Fat / adverse effects
Dietary Fats / pharmacology
Fructose / metabolism
Glucose / metabolism
Glucose Intolerance* / metabolism
Humans
Insulin / metabolism
Islets of Langerhans* / metabolism

Substances

Blood Glucose
Dietary Fats
Insulin
Fructose
Glucose

Abstract

Publication types

MeSH terms

Substances

Grants and funding