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The Taurine-Conjugated Bile Acid (TUDCA) Normalizes Insulin Secretion in Pancreatic β-Cells Exposed to Fatty Acids: The Role of Mitochondrial Metabolism

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Taurine 12

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1370))

Abstract

Bile acid tauroursodeoxycholic (TUDCA), formed from the association of ursodeoxycholic acid (UDCA) with taurine, has already been shown to increase mitochondrial biogenesis and cell survival, in addition to reduce reticulum stress markers in different cell types. However, its mechanism of action upon insulin secretion control in obesity is still unknown. In this sense, we seek to clarify whether taurine, associated with bile acid, could improve the function of the pancreatic β-cells exposed to fatty acids through the regulation of mitochondrial metabolism. To test this idea, insulin-producing cells (INS1-E) were exposed to a fatty acid mix containing 500 μM of each palmitate and oleate for 48 hours treated or not with 300 μM of TUDCA. After that, glucose-stimulated insulin secretion and markers of mitochondrial metabolism were evaluated. Our results showed that the fatty acid mix was efficient in inducing hyperfunction of INS1-E cells as observed by the increase in insulin secretion, protein expression of citrate synthase, and mitochondrial density, without altering cell viability. The treatment with TUDCA normalized insulin secretion, reducing the protein expression of citrate synthase, mitochondrial mass, and the mitochondrial membrane potential. This effect was associated with a decrease in the generation of mitochondrial superoxide and c-Jun N-terminal kinase (JNK) protein content. The findings are also consistent with the hypothesis that TUDCA normalizes insulin secretion by improving mitochondrial metabolism and redox balance. Thus, it highlights likely mechanisms of the action of this bile acid on the glycemic homeostasis reestablishment in obesity.

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Abbreviations

DM2 :

Type 2 diabetes mellitus

cAMP :

Cyclic adenosine monophosphate

CREB :

cAMP response element-binding protein

CS :

Citrate synthase

FA :

Fatty acids

FADH 2 :

Flavin adenine dinucleotide

GAPDH :

Glyceraldehyde-3-phosphate dehydrogenase

IHME :

Institute for Health Metrics and Evaluation

INS-1E :

Rat pancreatic ß-cell line

JNK :

c-Jun N-terminal kinase

NADH :

Nicotinamide adenine dinucleotide

NRF1 :

Nuclear respiratory factor 1

PGC1α :

Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha

PKA :

Protein kinase A

TFAM :

Mitochondrial transcription factor A

TUDCA :

tauroursodeoxycholic acid

UCP2 :

Uncoupling protein 2

UDCA :

Ursodeoxycholic acid

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Author information

Authors and Affiliations

  1. Obesity and Comorbidities Research Center (OCRC), Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil

    Thiago dos Reis Araujo, Dimitrius Santiago, Passos Simões, Fróes Guimarães, Claudio Cesar Zoppi & Everardo Magalhães Carneiro

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  1. Thiago dos Reis Araujo
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  2. Dimitrius Santiago
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  3. Passos Simões
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  4. Fróes Guimarães
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  5. Claudio Cesar Zoppi
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  6. Everardo Magalhães Carneiro
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Editor information

Editors and Affiliations

  1. Department of Pharmacology, University of South Alabama College of Medicine, Mobile, AL, USA

    Stephen W. Schaffer

  2. Department of Biology, College of Staten Island, New York, NY, USA

    Abdeslem El Idrissi

  3. Faculty of Bioscience and Biotechnology, Fukui Prefectural University, Eiheiji-cho, Fukui, Japan

    Shigeru Murakami

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dos Reis Araujo, T., Santiago, D., Simões, P., Guimarães, F., Zoppi, C.C., Carneiro, E.M. (2022). The Taurine-Conjugated Bile Acid (TUDCA) Normalizes Insulin Secretion in Pancreatic β-Cells Exposed to Fatty Acids: The Role of Mitochondrial Metabolism. In: Schaffer, S.W., El Idrissi, A., Murakami, S. (eds) Taurine 12. Advances in Experimental Medicine and Biology, vol 1370. Springer, Cham. https://doi.org/10.1007/978-3-030-93337-1_28

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