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Role of Mitochondria in Pancreatic Metabolism, Diabetes, and Cancer

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Exploring Pancreatic Metabolism and Malignancy

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Abstract

Ever since from the discovery of mitochondria, it attracted the field of medicine due to its involvement in numerous aspects of cellular metabolism. Mitochondria, the powerhouse of the cell, are extremely important for maintenance of several vital processes such as TCA cycle, generation of cellular energy source adenosine triphosphate (ATP), cell growth, cell death, and signal transduction. Therefore, it is evident that any type of mitochondrial perturbations would result in myriad of diseases. Mitochondrial diseases are also results from nuclear DNA mutations because most proteins involved in mitochondrial metabolism and mitochondrial DNA maintenance are nuclear encoded. Mitochondrial DNA variations are also observed in aging, diabetes, cancer, and neurological diseases such as Parkinson’s and Alzheimer’s diseases. So far, the research accentuated the relationship between mitochondrial dysfunction and multitude of diseases. Pancreas is one such organ that is frequently affected by mitochondrial perturbations. Over the past decade, significant amount of research has been done on mitochondria in pancreatic dysfunction. Heretofore, accumulating evidences suggest that pancreatitis, diabetes, and pancreatic cancer have highlighted the relationship with mitochondrial dysfunction. In this book chapter, we explore the advances that have been made toward identifying the mitochondria as therapeutic target in pancreatic malignancies including pancreatic metabolism, diabetes, and cancer.

Co-correspond author: Noble Kumar Talari.

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Abbreviations

αKG:

Alpha-ketoglutarate

β-Lap:

β-Lapachone

Ala:

Alanine

AM:

Adrenomedullin

ARE:

Antioxidant response element

ASK1:

Akt-stimulated phosphorylation of apoptosis signal-regulating kinase 1

Asp:

Aspartate

BPTES:

Bis-2-(5-phenylacetamido-1,3,4-thaidazole-2-yl) ethyl sulfide

Cit:

Citrate

Cys:

Cysteine

DON:

6-Diazo-5-oxo-L-norleucine

ER:

Endoplasmic reticulum

Fum:

Fumarate

GCL:

Glutamate cysteine ligase

GEM:

Gemcitabine

Gln:

Glutamine

Glu:

Glutamate

GLUD1:

Glutamate dehydrogenase

Gly:

Glycine

GOT:

Aspartate transaminase

GS:

Glutathione synthase

HA:

Hyaluronan or hyaluronic acid

HBP:

Hexosamine biosynthetic pathway

HIF:

Hypoxia inducible factors

IGF-1:

Insulin-responsive growth factor

Iso:

Isocitrate

Lac:

Lactate

LDHA:

Lactate dehydrogenase A

Mal:

Malate

MDH:

Malate dehydrogenase

Met:

Metformin

MMP:

Matrix metallo proteinase

NOX:

NADH oxidase

NQO1:

NADPH-quinone oxido-reductase 1

NR5A2:

Nuclear receptor 5 A2

NRF2:

Nuclear factor erythroid 2-related factor 2

OAA:

Oxaloacetate

OAA:

Oxaloacetic acid

PDAC:

Pancreatic ductal adenocarcinoma

PPP:

Pentose phosphate pathway

PTEN:

Phosphatase and tensin homolog

Pyr:

Pyruvate

R5P:

Ribose 5-phosphate

ROS:

Reactive oxygen species

Suc:

Succinate

T2DM:

Type2 diabetes mellitus

TCA:

Tricarboxylic acid cycle

UCP2:

Uncoupling protein 2

UDP-GlcNAC:

Uridine diphosphate N-acetylglucosamine

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Acknowledgements

Authors would like to acknowledge funding from DST-SERB (File number CRG/2018/001028) and DBT (File number BT/PR10319/BRB/10/1267/2013) to Prof. Naresh Babu V Sepuri. Noble Kumar Talari would like to acknowledge CSIR (09/414(1192)/2019-EMR-1) for the Research Associate fellowship. Ushodaya Mattam would like to acknowledge DBT (BT/PR19439/BIC/101/431/2016) for the fellowship. The authors also thank their lab members for suggestions.

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  1. Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, India

    Noble Kumar Talari, Ushodaya Mattam & Naresh Babu V. Sepuri

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  1. Noble Kumar Talari
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Correspondence to Noble Kumar Talari .

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  1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA

    Ganji Purnachandra Nagaraju

  2. Department of Animal Biology, University of Hyderabad, Hyderabad, Telangana, India

    Aramati BM Reddy

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Talari, N.K., Mattam, U., Sepuri, N.B.V. (2019). Role of Mitochondria in Pancreatic Metabolism, Diabetes, and Cancer. In: Nagaraju, G., BM Reddy, A. (eds) Exploring Pancreatic Metabolism and Malignancy. Springer, Singapore. https://doi.org/10.1007/978-981-32-9393-9_5

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