Phenformin Increases Insulin Binding to Human Cultured Breast Cancer Cells

Cohen, David; Pezzino, V.; Vigneri, Riccardo; Avola, Rosanna; D’Agata, Rosario; Polosa, P

doi:10.2337/diab.29.4.329

Cited by 15 publications

(6 citation statements)

References 7 publications

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“…Insulin binding to monocytes in our series was significantly lower than in normal subjects, and metformin treatment increased the number of insulin receptors on monocytes. These results agree with reports in vitro [2,3] and in vivo [17] and give a rationale for the use of metformin in association with insulin treatment. Our results show that this approach is of practical value since there was a 25.8% decrease in daily insulin requirement after metformin.…”

Section: Discussionsupporting

confidence: 91%

“…Peripheral hyperinsulinism may lead to down-regulation of insulin receptors [16] and thus make Type 1 diabetic patients less sensitive to the action of the exogenous hormone. Metformin improves insulin binding to target cells in vitro [2,3] and might be expected to improve insulin sensitivity in Type t diabetic patients. Insulin binding to monocytes in our series was significantly lower than in normal subjects, and metformin treatment increased the number of insulin receptors on monocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Biguanides lower blood glucose concentration, although in practical terms their effect is only evident in diabetes mellitus [1]. The underlying mechanism is not fully understood, but support for a peripheral action has been shown recently by an enhancement of insulin receptors in the presence of phenformin [2] and metformin [3]. Studies in vitro [2,3] have shown a rapid dosedependent effect of biguanides on insulin binding to target cells, unrelated to changes in blood glucose or insulin concentration as in the case of other drugs [3].…”

mentioning

confidence: 99%

“…The underlying mechanism is not fully understood, but support for a peripheral action has been shown recently by an enhancement of insulin receptors in the presence of phenformin [2] and metformin [3]. Studies in vitro [2,3] have shown a rapid dosedependent effect of biguanides on insulin binding to target cells, unrelated to changes in blood glucose or insulin concentration as in the case of other drugs [3]. This direct effect offers a more logical basis for earlier work showing sufficient potentiation of the peripheral [4] and hepatic effect to justify the use of biguanides in the treatment of Type 1 (insulin-dependent) diabetes mellitus.…”

mentioning

confidence: 99%

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Metformin reduces insulin requirement in Type 1 (insulin-dependent) diabetes

Pagano¹,

Tagliaferro

Carta

et al. 1983

Diabetologia

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The effect of metformin on Type 1 (insulin-dependent) diabetes has been assessed with the artificial pancreas. Fourteen Type 1 diabetic patients of normal body weight received in addition to their usual insulin therapy 850 mg metformin or placebo three times a day for 4-6 weeks. The sequence was placebo-metformin in eight patients and metformin-placebo in the other six. On the last day of metformin or placebo treatment, an artificial pancreas was used for about 36 h to assess insulin requirement. There was a 25.8% reduction in insulin requirement during metformin management despite slightly lower blood glucose levels (5.25 +/- 0.20 versus 5.98 +/- 0.18 mmol/l, p less than 0.01). Maximum reduction (about 50%) occurred 2 h after both lunch and dinner. There was no nocturnal effect. A marked decrease in specific insulin binding before metformin was found (0.56 +/- 0.27% to 10(7) monocytes versus 2.82 +/- 0.75 of control subjects) and significant increase after metformin (1.36 +/- 0.36%, p less than 0.05). There were no significant changes in blood lactate, total and HDL-cholesterol, triglycerides and C-peptide levels. These results show that insulin receptor binding is diminished in Type 1 diabetes, perhaps as a consequence of higher peripheral blood insulin levels and that metformin can improve binding, and so reduce the amount of insulin needed to reach euglycaemia. The insulin sparing effect is greatest after meals, and interference with intestinal absorption of sugars may also be important. It follows that metformin could be usefully administered to Type 1 diabetic patients with unimpaired liver and renal function to reduce their insulin requirement.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Metformin reduces insulin requirement in Type 1 (insulin-dependent) diabetes

Pagano¹,

Tagliaferro

Carta

et al. 1983

Diabetologia

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“…In vitro studies with various cells indicate that the biguanides, at concentrations that are effective in vivo, increase insulin binding to its receptors in vitro (26)(27)(28)(29)(30). Studies of the effect of metformin on insulin receptors have been performed in humans.…”

Section: Mechanism Of Actionmentioning

confidence: 98%

Role of metformin in treatment of diabetes mellitus

Vigneri

Goldfine

1987

Diabetes Care

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Metformin, a biguanide antidiabetic agent that can be administered either alone or in combination with sulfonylureas, has been extensively used in Europe and Canada. The mechanism of action of metformin and other biguanides is not completely understood, but recent in vitro and in vivo studies suggest that metformin may act in part by both increasing the binding of insulin to its receptor and potentiating insulin action. Metformin, because of its chemical structure, does not interact with the liver and has a short half-life. Consequently, lactic acidosis, which is a rare complication of metformin, has not been associated with the proper use of this drug. In addition to its antidiabetic actions, metformin causes weight loss in obese diabetic patients and may be useful in managing associated lipid disorders.

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The effect of phenformin and other adenosine triphosphate (ATP)‐lowering agents on insulin binding to IM‐9 human cultured lymphocytes

Vigneri

Maddux²,

Goldfine

1984

J of Cellular Biochemistry

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In the present study, we investigated the mechanism by which the antidiabetic drug phenformin increases insulin binding to its receptors in IM-9 human cultured lymphocytes. After a 24-hr preincubation, phenformin induced a twofold increase in specific 125I-insulin binding, and removal of phenformin was followed 6 hr later by a return in binding to control levels. This effect of phenformin on insulin binding was not a consequence of either inhibition of cell growth, changes in cellular cyclic adenosine monophosphate (AMP) levels, or changes in guanosine triphosphate (GTP) content. Since phenformin is known to inhibit various aspects of cellular energy metabolism, the relationship between 125I-insulin binding and energy metabolism in IM-9 cells was investigated. The phenformin-induced increase in insulin binding to IM-9 cells was related to a time- and dose-dependent decrease in ATP levels. Other agents that lowered ATP levels, including antimycin, dinitrophenol, and 2-deoxyglucose, also raised insulin binding. These studies indicated, therefore, that phenformin enhances insulin binding to receptors on IM-9 cells and that this effect on insulin receptors may be related to alterations in metabolic functions that are reflected by a lowering of ATP levels.

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Phenformin Increases Insulin Binding to Human Cultured Breast Cancer Cells

Cited by 15 publications

References 7 publications

Metformin reduces insulin requirement in Type 1 (insulin-dependent) diabetes

Metformin reduces insulin requirement in Type 1 (insulin-dependent) diabetes

Role of metformin in treatment of diabetes mellitus

The effect of phenformin and other adenosine triphosphate (ATP)‐lowering agents on insulin binding to IM‐9 human cultured lymphocytes

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