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Diabetes with Pancreatic Ductal Adenocarcinoma

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Exploring Pancreatic Metabolism and Malignancy

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Abstract

Diabetes and pancreatic ductal adenocarcinoma (PDAC) are common diseases and affect the same organ, pancreas. PDAC has a poor prognosis and response to conservative therapy. Diabetes is recently been correlated with mortality and morbidity from PDAC. The association between diabetes and PDAC stems from the structural association between the endocrine and exocrine pancreas and aberrant expression of hormones from islets. It can also result from other etiological factors including stress, inflammation, smoking, alcohol consumption, change in the diet, as well as inherited syndromes that affect PDAC tissue. Epidemiological evidence suggests that diabetes increases the risk for PDAC development. Insulin resistance, hyperinsulimenia, hyperglycemia, chronic inflammation, and their elementary mechanisms can contribute to the development of diabetes-associated PDAC. Signal transduction pathways that regulate metabolic functions also play a crucial role in the development of PDAC, promoting tumor proliferation, cell growth, differentiation, angiogenesis, and metastasis. In another way, PDAC is also a causative factor for diabetes, although the mechanisms are not well understood. Effective biomarkers might thus help detect the increased risk of PDAC. Furthermore, greater understanding of the pathological mechanisms linking diabetes to PDAC could guide the development of new therapeutic agents to prevent diabetes associated with PDAC.

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Abbreviations

4-HNE:

4-hydroxyl-2-nonenal

Akt:

Protein kinase B

AMP:

Adenosine monophosphate

AMPK:

AMP-activated protein kinase

ATP:

Adenosine triphosphate

ASK-1:

Apoptosis signaling kinase-1

CI:

Confidence interval

COX2:

Cyclooxygenase

DNA:

Deoxyribonucleic acid

ERK:

Extracellular signal-regulated kinases

ETC:

electron transport chain

FGD-PET:

F-18-Fluoro-deoxyglucose (FDG)-positron emission tomography (PET)

FTZ-F1:

Fushi-tarazu factor-1

GI:

Glycemic index

GLUT:

Glucose transporter

GWAS:

Genome-wide association studies

HNF-3β:

Hepatocyte nucleoside factor-3β

IER:

Intermittent energy restriction

IGFBP-1:

Insulin growth factor-binding protein-1

IGF:

Insulin growth factor

IGFR:

Insulin growth factor receptors

IKK:

Inhibitor of kB kinase

IL-6:

Interleukin-6

IL-8:

Interleukin-8

IR:

Insulin receptor

IRS:

Insulin receptor substrate 1

JNK:

c-Jun N-terminal kinases

LKB1:

Liver kinase B1

LOOH:

Lipid hydroperoxides

LRH1:

Liver receptor homolog-1

MDA:

Malondialdehyde

MEK:

Mitogen-activated protein kinase

MMP-7:

Matrix metalloproteinase-7

mTOR:

Mammalian target of rapamycin

NADPH:

Nicotinamide adenine dinucleotide

NF-κB:

Nuclear factor kappa B

NO:

Nitric oxide

NR5A2:

Nuclear receptor superfamily member

PDAC:

Pancreatic ductal adenocarcinoma

PDX-1:

Pancreatic duodenal homeobox

PI3K:

Phosphatidylinositol 3 kinase

RIP-1:

Receptor interacting protein

RO:

Alkoxyl radical

ROS:

Reactive oxygen species

RR:

Relative risk

SO4:

Sulfate radical

SODD:

Silencer of death domain

STAT:

Signal transducer and activator of transcription 3

TNF-α:

Tumor necrosis factor-α

TRADD:

TNF receptor-associated death domain

VAT:

Vascular adipose tissue

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Department of Bioscience and Biotechnology, Banasthali University, Vanasthali, Rajasthan, India

    Gowru Srivani, Begum Dariya & Afroz Alam

  2. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Ganji Purnachandra Nagaraju

Authors
  1. Gowru Srivani
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  2. Begum Dariya
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  3. Afroz Alam
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  4. Ganji Purnachandra Nagaraju
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Corresponding author

Correspondence to Ganji Purnachandra Nagaraju .

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Editors and Affiliations

  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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Srivani, G., Dariya, B., Alam, A., Nagaraju, G.P. (2019). Diabetes with Pancreatic Ductal Adenocarcinoma. In: Nagaraju, G., BM Reddy, A. (eds) Exploring Pancreatic Metabolism and Malignancy. Springer, Singapore. https://doi.org/10.1007/978-981-32-9393-9_7

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