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Prof. Dr. Naotake Hashimoto

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Department of Diabetes, Endocrine and Metabolic Diseases, Tokyo Women's Medical University Yachiyo Medical Center, Chiba 276-8524, Japan
Interests: cancer; diabetes; molecular mechanisms; insulin resistance; hyperglycemia; oxidative stress; growth factors
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Dear Colleagues,

Cancer remains one of the leading causes of death and has a high global prevalence. According to published studies, the risk and mortality rate of cancer has been found to be significantly increased in patients with diabetes and obesity. The mechanisms underlying this increase have been investigated by many researchers, and inflammation, endocrine effects, hyperglycemia, insulin resistance, and hyperinsulinemia associated with diabetes and obesity have been proposed. Metformin, which is produced from French lilac, is an oral biguanide and has been prescribed to over 120 million patients with diabetes or polycystic ovary syndrome all over the world. Interesting data on metformin have been reported, and this medicine has been found to exert protective effects against the promotion or incidence of cancers. In this Special Issue, updates in our understanding of the molecular mechanisms of these factors in cancers in diabetes patients will be reviewed and discussed in the context of the possibility of overcoming cancer in the near future.

Prof. Naotake Hashimoto
Guest Editor

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Keywords

cancer
diabetes
molecular mechanisms
gene expression
post-transcriptional modification
metastasis
hypoxia-induced factors
oxidative stress

Published Papers (2 papers)

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Review

33 pages, 1680 KiB

Open AccessReview

Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?

by Anna Gabryanczyk, Sylwia Klimczak, Izabela Szymczak-Pajor and Agnieszka Śliwińska

Int. J. Mol. Sci. 2021, 22(12), 6444; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126444 - 16 Jun 2021

Cited by 12 | Viewed by 3153

Abstract

There is mounting evidence that type 2 diabetes mellitus (T2DM) is related with increased risk for the development of cancer. Apart from shared common risk factors typical for both diseases, diabetes driven factors including hyperinsulinemia, insulin resistance, hyperglycemia and low grade chronic inflammation are of great importance. Recently, vitamin D deficiency was reported to be associated with the pathogenesis of numerous diseases, including T2DM and cancer. However, little is known whether vitamin D deficiency may be responsible for elevated cancer risk development in T2DM patients. Therefore, the aim of the current review is to identify the molecular mechanisms by which vitamin D deficiency may contribute to cancer development in T2DM patients. Vitamin D via alleviation of insulin resistance, hyperglycemia, oxidative stress and inflammation reduces diabetes driven cancer risk factors. Moreover, vitamin D strengthens the DNA repair process, and regulates apoptosis and autophagy of cancer cells as well as signaling pathways involved in tumorigenesis i.e., tumor growth factor β (TGFβ), insulin-like growth factor (IGF) and Wnt-β-Cathenin. It should also be underlined that many types of cancer cells present alterations in vitamin D metabolism and action as a result of Vitamin D Receptor (VDR) and CYP27B1 expression dysregulation. Although, numerous studies revealed that adequate vitamin D concentration prevents or delays T2DM and cancer development, little is known how the vitamin affects cancer risk among T2DM patients. There is a pressing need for randomized clinical trials to clarify whether vitamin D deficiency may be a factor responsible for increased risk of cancer in T2DM patients, and whether the use of the vitamin by patients with diabetes and cancer may improve cancer prognosis and metabolic control of diabetes. Full article

(This article belongs to the Special Issue Mechanisms of Cancer Development in Diabetes)

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17 pages, 1403 KiB

Open AccessReview

Diabetes, Antidiabetic Medications and Cancer Risk in Type 2 Diabetes: Focus on SGLT-2 Inhibitors

by Mariusz Dąbrowski

Int. J. Mol. Sci. 2021, 22(4), 1680; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041680 - 07 Feb 2021

Cited by 17 | Viewed by 4448

Abstract

In the last decade, cancer became the leading cause of death in the population under 65 in the European Union. Diabetes is also considered as a factor increasing risk of cancer incidence and mortality. Type 2 diabetes is frequently associated with being overweight and obese, which also plays a role in malignancy. Among biological mechanisms linking diabetes and obesity with cancer hyperglycemia, hyperinsulinemia, insulin resistance, increased levels of growth factors, steroid and peptide hormones, oxidative stress and increased activity of pro-inflammatory cytokines are listed. Antidiabetic medications can modulate cancer risk through directly impacting metabolism of cancer cells as well as indirectly through impact on risk factors of malignancy. Some of them are considered beneficial (metformin and thiazolidinedions—with the exception of bladder cancer); on the other hand, excess of exogenous insulin may be potentially harmful, while other medications seem to have neutral impact on cancer risk. Inhibitors of the sodium-glucose cotransporter-2 (SGLT-2) are increasingly used in the treatment of type 2 diabetes. However, their association with cancer risk is unclear. The aim of this review was to analyze the anticancer potential of this class of drugs, as well as risks of site-specific malignancies associated with their use. Full article

(This article belongs to the Special Issue Mechanisms of Cancer Development in Diabetes)

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