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Review
. 2014 May 4;5(3):251-64.
doi: 10.1111/jdi.12208. Epub 2014 Mar 5.

Cancer biology in diabetes

Shi Sen  1 , Yanzheng He  2 , Daisuke Koya  3 , Keizo Kanasaki  3
Affiliations
Review

Cancer biology in diabetes

Shi Sen et al. J Diabetes Investig. .

Abstract

Diabetes is a serious metabolic disease that causes multiple organ dysfunctions. Recent evidence suggests that diabetes could contribute to the initiation and progression of certain cancers in addition to the classic diabetic complications. Furthermore, some of the drugs used clinically to treat patients with diabetes might affect cancer initiation, progression and mortality. The recent discovery of the possible anticancer effects of metformin, a classic antidiabetic drug, has led physicians and scientists to reconsider the interaction between diabetes and cancer. In the present review, we analyze recent reports in this field, and explore possible mechanistic links between diabetes and cancer biology.

Keywords: Antidiabetic drugs; Cancer; Diabetes.

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Figures

Figure 1
Figure 1
Diverse mechanistic pathways of metformin. Metformin reduces adenosine triphosphate (ATP) production, increasing the cellular adenosine monophosphate (AMP)‐to‐ATP ratio, which leads to the activation of the liver kinase B1 (LKB1)–AMP activated protein kinase (AMPK) signaling pathway. Subsequently, LKB1 activates AMPK. AMPK inhibits mammalian target of rapamycin complex 1 (mTORC1) directly and the mTOR‐inhibitor through tuberous sclerosis complex (TSC)1/2 activation. Such mTORC1‐inhibition results in the inhibition of several carcinogenic molecules, such as ribosomal protein S6 kinase (S6K) and hypoxia‐inducible factor‐1α (HIF‐1α). Several growth factors induce protein‐kinase B (PKB)/Akt activation and counteract with AMPK‐mediated TSC1/2 activation. Alternatively, metformin inhibits Rag‐guanosine triphosphatase (GTPase), which activates mTORC1.
Figure 2
Figure 2
Glucogen‐like peptide‐1 and cancer. Mechanism of GLP‐1‐potentiated insulin secretion in β‐cells and a possible cancer pathway. AC, adenylatecyclase; ADP, adenosine diphosphate; ATP, adenosine triphosphate; IGF‐BP3, insulin‐like growth factor binding‐protein 3; cAMP, cyclic adenosine monophosphate; IGF, insulin‐like growth factor; PI3‐Akt; phosphatidyl‐inositol 3‐kinase‐Protein Kinase B; PKA, protein kinase A; PPARγ, peroxisome proliferator‐activated receptor‐γ; Ras‐ERK, renin–angiotensin system–extracellular regulated protein kinases.
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