Insulin in aging and cancer: antidiabetic drug diabenol as geroprotector and anticarcinogen

Popovich, Irina G.; Zabezhinski, Mark A.; Egormin, Peter A.; Tyndyk, Margarita L.; Anikin, Ivan V.; Спасов, А. А.; Semenchenko, Anna V.; Yashin, Anatoly I.; Anisimov, Vladimir N.

doi:10.1016/j.biocel.2004.08.002

Cited by 21 publications

(21 citation statements)

References 44 publications

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“…The serum IGF-1 decrease was accompanied with insulin decrease in all experimental groups (non-significant in the control group), glycemia, however, was not changed. Metformin and other biguanides impact on insulin/IGF-1 signaling has been suggested as a mechanism involved both in ageing and carcinogenesis by Anisimov group [30,17,31], the effective dose, however, has to be found by further research.…”

Section: Discussionmentioning

confidence: 99%

Metformin in chemically-induced mammary carcinogenesis in rats

Bojková¹,

Orendáš²,

Garajová³

et al. 2009

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In this paper the chemopreventive effect of peroral antidiabetic metformin in mammary carcinogenesis in female SpragueDawley rats was evaluated. Mammary carcinogenesis was induced by N-methyl-N-nitrosourea (NMU) administered in two intraperitoneal doses each per 50 mg/kg b.w. between 43.-55. postnatal days. Metformin was administered in drinking water (at a concentration of 50 µg/ml and 500 µg/ml) 13 days before the first NMU dose until the termination of the experiment. During the experiment the animals were weekly weighed and palpated for the presence of mammary tumors, the incidence, latency, tumor frequency, and tumor volume were recorded. The experiment was terminated 18 weeks after the first NMU dose, basic tumor growth parameters and metabolic and hormonal variables were evaluated. Metformin did not significantly alter the tumor growth although a delay in tumor onset was recorded after higher metformin dose. Metformin altered metabolic and hormonal variables. Insulinemia decreased after both metformin doses in comparison with intact rats without changes in glycemia, triacylglycerols concentration was decreased in liver and increased in serum when compared to intacts. Higher metformin dose attenuated lipoperoxidation in liver.

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Section: Discussionmentioning

confidence: 99%

Metformin in chemically-induced mammary carcinogenesis in rats

Bojková¹,

Orendáš²,

Garajová³

et al. 2009

neo

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“…Recently, it was shown that metformin decreases platelet superoxide anion production in diabetic patients [224]. There are observations that diabenol has similar effects [225]. Metformin increased glutathione (GSH) levels and diminished lipid peroxidation of T cells in mice; thus, the decrease of oxidative stress inhibited proliferation of T cells [226].…”

Section: Mechanisms Of Effects Of Antidiabetic Biguanides On Aginmentioning

confidence: 99%

The key role of growth hormone–insulin–IGF-1 signaling in aging and cancer

Anisimov

Bartke

2013

Critical Reviews in Oncology/Hematology

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183

123

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Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors in aging. GH/Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules that have been linked to longevity include daf-2 and InR and their homologues in mammals, and inactivation of the corresponding genes increases lifespan in nematodes, fruit flies and mice. The life-prolonging effects of caloric restriction are likely related to decreasing IGF-1 levels. Evidence has emerged that antidiabetic drugs are promising candidates for both lifespan extension and prevention of cancer. Thus, antidiabetic drugs postpone spontaneous carcinogenesis in mice and rats, as well as chemical and radiation carcinogenesis in mice, rats and hamsters. Furthermore, metformin seems to decrease the risk for cancer in diabetic patients.

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“…The effects of new antidiabetic drug Diabenol® (9-β-diethyl-aminoethyl-2,3-dihydro-imidazo-(1, 2-α) benzi-midazol dihydrochloride) on life span of NMRI and transgenic HER-2/neu mice have been studied [71]. Diabenol was synthesized in Rostov State University and its hypoglycemic activity was evaluated as 1.5 times more effective than of maninil (glibenclamide) and equal to the effect of glyclazide (pioglitazone) in rats, rabbits and dogs [77,78].…”

Section: Introductionmentioning

confidence: 99%

Metformin for aging and cancer prevention

Anisimov

2010

Aging

Self Cite

133

102

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Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors in aging. Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules that have been linked to longevity include daf-2 and InR and their homologues in mammals, and inactivation of the corresponding genes increases life span in nematodes, fruit flies and mice. It is possible that the life-prolonging effect of caloric restriction is due to decreasing IGF-1 levels. Evidence has emerged that antidiabetic drugs are promising candidates for both life span extension and prevention of cancer. Thus, antidiabetic drugs postpone spontaneous carcinogenesis in mice and rats, as well as chemical and radiation carcinogenesis in mice, rats and hamsters. Furthermore metformin seems to decrease cancer risk in diabetic patients.

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Insulin in aging and cancer: antidiabetic drug diabenol as geroprotector and anticarcinogen

Cited by 21 publications

References 44 publications

Metformin in chemically-induced mammary carcinogenesis in rats

Metformin in chemically-induced mammary carcinogenesis in rats

The key role of growth hormone–insulin–IGF-1 signaling in aging and cancer

Metformin for aging and cancer prevention

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