Gut Metabolite Trimethylamine N-Oxide Protects INS-1 β-Cell and Rat Islet Function under Diabetic Glucolipotoxic Conditions

Krueger, Emily S.; Beales, Joseph L.; Russon, Kacie B.; Elison, Weston S.; Davis, Jordan R.; Hansen, Jackson M.; Neilson, Andrew P.; Hansen, Jason M.; Tessem, Jeffery S.

doi:10.3390/biom11121892

Open AccessArticle

Gut Metabolite Trimethylamine N-Oxide Protects INS-1 β-Cell and Rat Islet Function under Diabetic Glucolipotoxic Conditions

by

Emily S. Krueger

¹

,

Joseph L. Beales

^1,†,

Kacie B. Russon

¹,

Weston S. Elison

^1,‡

,

Jordan R. Davis

¹,

Jackson M. Hansen

²,

Andrew P. Neilson

³

,

Jason M. Hansen

² and

Jeffery S. Tessem

^1,*

¹

Department of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USA

²

Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA

³

Plants for Human Health Institute, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC 28081, USA

^*

Author to whom correspondence should be addressed.

^†

Current Affiliation: Medical Education Program, Paul L. Foster School of Medicine, El Paso, TX 79905, USA.

^‡

Current Affiliation: Biomedical Sciences Program, University of California San Diego, La Jolla, CA 92093, USA.

Biomolecules 2021, 11(12), 1892; https://doi.org/10.3390/biom11121892

Submission received: 2 November 2021 / Revised: 11 December 2021 / Accepted: 14 December 2021 / Published: 17 December 2021

(This article belongs to the Special Issue The Pancreatic Beta Cell)

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Abstract

Serum accumulation of the gut microbial metabolite trimethylamine N-oxide (TMAO) is associated with high caloric intake and type 2 diabetes (T2D). Impaired pancreatic β-cell function is a hallmark of diet-induced T2D, which is linked to hyperglycemia and hyperlipidemia. While TMAO production via the gut microbiome-liver axis is well defined, its molecular effects on metabolic tissues are unclear, since studies in various tissues show deleterious and beneficial TMAO effects. We investigated the molecular effects of TMAO on functional β-cell mass. We hypothesized that TMAO may damage functional β-cell mass by inhibiting β-cell viability, survival, proliferation, or function to promote T2D pathogenesis. We treated INS-1 832/13 β-cells and primary rat islets with physiological TMAO concentrations and compared functional β-cell mass under healthy standard cell culture (SCC) and T2D-like glucolipotoxic (GLT) conditions. GLT significantly impeded β-cell mass and function by inducing oxidative and endoplasmic reticulum (ER) stress. TMAO normalized GLT-mediated damage in β-cells and primary islet function. Acute 40µM TMAO recovered insulin production, insulin granule formation, and insulin secretion by upregulating the IRE1α unfolded protein response to GLT-induced ER and oxidative stress. These novel results demonstrate that TMAO protects β-cell function and suggest that TMAO may play a beneficial molecular role in diet-induced T2D conditions.

Keywords: beta cell; islet; glucolipotoxicity (GLT); glucose stimulated insulin secretion (GSIS); unfolded protein response (UPR); type 2 diabetes (T2D)

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MDPI and ACS Style

Krueger, E.S.; Beales, J.L.; Russon, K.B.; Elison, W.S.; Davis, J.R.; Hansen, J.M.; Neilson, A.P.; Hansen, J.M.; Tessem, J.S. Gut Metabolite Trimethylamine N-Oxide Protects INS-1 β-Cell and Rat Islet Function under Diabetic Glucolipotoxic Conditions. Biomolecules 2021, 11, 1892. https://doi.org/10.3390/biom11121892

AMA Style

Krueger ES, Beales JL, Russon KB, Elison WS, Davis JR, Hansen JM, Neilson AP, Hansen JM, Tessem JS. Gut Metabolite Trimethylamine N-Oxide Protects INS-1 β-Cell and Rat Islet Function under Diabetic Glucolipotoxic Conditions. Biomolecules. 2021; 11(12):1892. https://doi.org/10.3390/biom11121892

Chicago/Turabian Style

Krueger, Emily S., Joseph L. Beales, Kacie B. Russon, Weston S. Elison, Jordan R. Davis, Jackson M. Hansen, Andrew P. Neilson, Jason M. Hansen, and Jeffery S. Tessem. 2021. "Gut Metabolite Trimethylamine N-Oxide Protects INS-1 β-Cell and Rat Islet Function under Diabetic Glucolipotoxic Conditions" Biomolecules 11, no. 12: 1892. https://doi.org/10.3390/biom11121892

APA Style

Krueger, E. S., Beales, J. L., Russon, K. B., Elison, W. S., Davis, J. R., Hansen, J. M., Neilson, A. P., Hansen, J. M., & Tessem, J. S. (2021). Gut Metabolite Trimethylamine N-Oxide Protects INS-1 β-Cell and Rat Islet Function under Diabetic Glucolipotoxic Conditions. Biomolecules, 11(12), 1892. https://doi.org/10.3390/biom11121892

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Gut Metabolite Trimethylamine N-Oxide Protects INS-1 β-Cell and Rat Islet Function under Diabetic Glucolipotoxic Conditions

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