Mitogenic action of insulin: friend, foe or ‘frenemy’?

Draznin, Boris

doi:10.1007/s00125-009-1558-6

Cited by 73 publications

(66 citation statements)

References 28 publications

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“…190 In parallel, it was also shown in previous in vitro studies that the IR, predominantly the more mitogenic IR-A isoform, is overexpressed in many types of cancer, [191][192][193][194][195] and insulin as well as insulin analogues appears to be able to stimulate the growth of various tumour cells in vitro through IR-A, although the existing data revealed some heterogeneity. [196][197][198][199] Here, we will focus on insulin analogues in humans trying to clarify the safety concerns raised by the in vitro studies. Most human data are available for insulin glargine, a long-acting insulin analogue first approved in 2000 in the European Union (EU) and in 2003 in the United States.…”

Section: Insulin-based Therapies and Cancer Riskmentioning

confidence: 99%

Antihyperglycaemic therapies and cancer risk

Lutz

Staiger

Fritsche

et al. 2014

Diabetes and Vascular Disease Research

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Aims: This review is aimed at highlighting the potential mitogenic/tumour growth-promoting or antimitogenic/tumour growth-inhibiting effects of the main antihyperglycaemic drug classes. Methods: We review and discuss the most current studies evaluating the association between antidiabetic medications used in clinical practice and malignancies as described so far. Results: Metformin seems to be the only antidiabetic drug to exert protective effects both on monotherapy and also when combined with other oral antidiabetic drugs or insulins in several site-specific cancers. In contrast, several other drug classes may increase cancer risk. Some reason for concern remains regarding sulphonylureas and also the incretinbased therapies regarding pancreas and thyroid cancers and the sodium glucose cotransporter-2 inhibitors as well as pioglitazone regarding bladder cancer. The majority of meta-analyses suggest that there is no evidence for a causal relationship between insulin glargine and elevated cancer risk, although the studies have been controversially discussed. For α-glucosidase inhibitors and glinides, neutral or only few data upon cancer risk exist. Conclusion: Although the molecular mechanisms are not fully understood, a potential risk of mitogenicity and tumour growth promotion cannot be excluded in case of several antidiabetic drug classes. However, more large-scale, randomized, well-designed clinical studies with especially long follow-up time periods are needed to get reliable answers to these safety issues.

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Section: Insulin-based Therapies and Cancer Riskmentioning

confidence: 99%

Antihyperglycaemic therapies and cancer risk

Lutz

Staiger

Fritsche

et al. 2014

Diabetes and Vascular Disease Research

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“…FTase exclusion during tumor progression had a restricted inhibitory effect [225]. The induction of FTase by hyperinsulinemia may partly account for the proliferative and atherogenic effects of insulin [226]. FTase also plays a significant role in progeria (Hutchinson-Gilford syndrome), a process of accelerated aging in which patients die prematurely due to atherosclerotic complications.…”

Section: Farnesyltransferase (Protein Farnesyltransferase)mentioning

confidence: 99%

Enzymatic Targets in Atherosclerosis

Fuior¹,

Trusca²,

Roman³

et al. 2015

J Mol Genet Med

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Atherosclerosis, a prime cause of mortality across the developed societies, was targeted by diverse therapeutic strategies. These evolved in response to the complex etiology and evolution of the disease. Many enzymes are associated with atherosclerosis, either in the main stream of lipid biosynthesis and transport or in the collateral and intertwined pathways of oxidative stress, inflammation, vascular remodeling or chromatin stability and are therefore revised herein. Enzyme exploration led to important developments. At the beginning, there were the statins, derived as inhibitors of hydroxy-methyl-glutaryl CoA (HMG-CoA) reductase, currently used widely to decrease lipid levels. At the other end, the inhibitors of the recently discovered proprotein convertase subtilisin/kexin type 9 (PCSK9) are awaiting the validation in clinical trials with great hopes for the future. In between, one can find some palliatives, as aspirin, an inhibitor of cyclooxygenase (COX), but also many invalidated candidates. Classical pharmacological data and newer approaches, like genetic knockouts in murine atherosclerosis models, are reviewed in order to appreciate the involvement of a particular enzyme in atherogenesis. However, the pursuit of an efficacious drug has been long and, in many cases, disappointing. Conclusions can be drawn from the overview of both successes and failures, in a quest for the best.

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“…This response becomes pathological in response to endogenous or exogenous hyperinsulinemia [142]. effect, but it can also change its mitogenic potency [143].…”

Section: Metabolic and Mitogenic Potential Of Insulin Therapymentioning

confidence: 99%

Evolution of Insulin Development: Focus on Key Parameters

Tibaldi

2012

Adv Therapy

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Mitogenic action of insulin: friend, foe or ‘frenemy’?

Cited by 73 publications

References 28 publications

Antihyperglycaemic therapies and cancer risk

Antihyperglycaemic therapies and cancer risk

Enzymatic Targets in Atherosclerosis

Evolution of Insulin Development: Focus on Key Parameters

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