Diabetes-associated dysregulated cytokines and cancer

Abstract

Epidemiological data demonstrate that patients with diabetes have an augmented risk of developing various types of cancers, accompanied by higher mortality. A number of mechanisms for this connection have been hypothesized, such as insulin resistance, hyperinsulinemia, hyperglycemia, and increased inflammatory processes. Apart from these potential mechanisms, several diabetes-associated dysregulated cytokines might be implicated in the link between diabetes and cancer. In fact, some inflammatory cytokines, e.g. TNF-α, IL-6 and leptin, have been revealed to play important roles in both initiation and progression of tumor. Here, we depict the role of these cytokines in key events of carcinogenesis and cancer development, including their capability to induce oxidative stress, inflammation, their participation in epithelial mesenchymal transition (EMT), angiogenesis, and metastasis. Finally, we will also highlight the existing knowledge in terms of the involvement of these cytokines in different cancer types and comment on potential significances for future clinical applications.

Differences of Angiogenesis Factors in Tumor and Diabetes Mellitus

“…8 In the early stage of diabetes, bFGF may increase, but in the long-term highglucose environment, bFGF can covalently bind with reducing sugar to form glycated fibroblast growth factor (gFGF), and this process may be an important reason for the decline of EPCs function. FGF-related therapies in tumors: HRGP attenuates the effects of FGF; in diabetes: PGE1 can effectively improve the angiogenic characteristics of bFGF in patients with diabetes, 59 and Leptin can increase the release of bFGF, 20 so these substances may be used as related therapeutic drugs. Besides, preventing the formation of gFGF or reducing gFGF may become a new target for the treatment of diabetic microangiopathy.…”

“…Plasminogen activator inhibitor-1 (PAI-1), a major physiological inhibitor of endogenous plasminogen activators, is synthesized by perivascular cells and is extremely unstable in vitro and in vivo, but can be stabilized by binding to vitronectin and affects angiogenesis by interacting with the u-PA receptor. 20 PAI-1 is highly expressed in both diabetes and tumor, but its effects are different: in diabetes, it impresses angiogenesis and promotes the formation of atherosclerotic plaques; 69 however, its effect on tumor has a dual nature: PAI-1 promotes angiogenesis by inhibiting PA at the physiological level; However, it can inhibit tumor angiogenesis at the pharmacological level, 20 but the mechanism of this phenomenon still needs further clarification.…”

“…18 Tumor and diabetes mellitus themselves have many common metabolic risk factors, such as high insulin, high insulin-like growth factor, etc., and it has been proved that the occurrence and development mechanism of the two are closely related. 19,20 Therefore, in theory, the two should show similar performances. Then, why the diabetes patients mainly show inhibition of angiogenesis, while the tumor patients show obvious enhancement of angiogenesis, which promotes its development and metastasis, should be analyzed from various factors affecting angiogenesis.…”

Оцінка Прогнозованого Ризику Онкологічних Захворювань У Хворих На Цукровий Діабет 2-Го Типу

“…Вплив ожиріння на розвиток КРР зумовлений поєднаним впливом цитокінового дисбалансу (прозапальних цитокінів: фактора некрозу пухлин α (TNF-α), інтерлейкіну-6 (IL-6), IL-8, IL-18 та ін.) [19] та дисбіозом кишечника, недостатністю грампозитивних бактерій, що мають протизапальні властивості, регулюють метаболізм білків та ензимів, а також, пригнічуючи ядерний фактор епітеліоцитів товстого кишечника (NF-κB), впливають на експресію генів -регуляторів імунної відповіді, апоптозу та клітинного циклу [20].…”

Non-hereditary risk factors associated with pancreatic cancer: a focus on obesity and diabetes

“…Adipose tissue is also implicated in the development of chronic metabolic diseases such as diabetes, especially type 2 diabetes mellitus, and a number of mechanisms have been hypothesized linking diabetes and cancer such as insulin resistance, hyperinsulinemia, hyperglycemia, and increased inflammatory processes. The same pro-inflammatory cytokines increased in obesity are also increased in patients with type 2 diabetes and are implicated in carcinogenesis including TNF-α, IL-6, leptin, C-reactive protein (CRP), and adiponectin, a cytokine produced by adipose tissue and associated with insulin sensitivity and therefore a cytokine with protective effects against the development of type 2 diabetes (Wu et al, 2016;Saeedi et al, 2019) [12,13].…”