Biguanide (Experimenteller Teil)

Beckmann, R

doi:10.1007/978-3-642-65265-3_8

Cited by 19 publications

(6 citation statements)

References 285 publications

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“…A vast selection of guanidine derivatives was then synthesised and evaluated, but enthusiasm was dampened by their lesser glucose-lowering efficacy in non-diabetic animals compared with agents that stimulate insulin secretion [34,35]. However, studies in human maturity-onset diabetes indicated greater glucose-lowering efficacy of phenformin compared with other biguanides and this agent gained global popularity as an alternative to sulfonylureas, especially in the USA [36][37][38].…”

Section: The Biguanide Opportunitymentioning

confidence: 99%

Metformin: historical overview

2017

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Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes. Its history is linked to Galega officinalis (also known as goat's rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose. Guanidine derivatives, including metformin, were synthesised and some (not metformin) were used to treat diabetes in the 1920s and 1930s but were discontinued due to toxicity and the increased availability of insulin. Metformin was rediscovered in the search for antimalarial agents in the 1940s and, during clinical tests, proved useful to treat influenza when it sometimes lowered blood glucose. This property was pursued by the French physician Jean Sterne, who first reported the use of metformin to treat diabetes in 1957. However, metformin received limited attention as it was less potent than other glucose-lowering biguanides (phenformin and buformin), which were generally discontinued in the late 1970s due to high risk of lactic acidosis. Metformin's future was precarious, its reputation tarnished by association with other biguanides despite evident differences. The ability of metformin to counter insulin resistance and address adult-onset hyperglycaemia without weight gain or increased risk of hypoglycaemia gradually gathered credence in Europe, and after intensive scrutiny metformin was introduced into the USA in 1995. Long-term cardiovascular benefits of metformin were identified by the UK Prospective Diabetes Study (UKPDS) in 1998, providing a new rationale to adopt metformin as initial therapy to manage hyperglycaemia in type 2 diabetes. Sixty years after its introduction in diabetes treatment, metformin has become the most prescribed glucose-lowering medicine worldwide with the potential for further therapeutic applications.

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Section: The Biguanide Opportunitymentioning

confidence: 99%

Metformin: historical overview

2017

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“…It is noteworthy that studies of metformin distribution in mice showed a measurable accumulation of 14 C metformin in brain tissue two hours after a single oral dose (150 mg/kg) [209]. The studies revealed that orally administered metformin increases brain AMPK activation [142].…”

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

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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“…Results are expressed as mean _+ SEM with the corresponding number of animals in parentheses Table 4. Beckmann [21] Sch~ifer [22] Chase and Yubbs [7] DeGaldeano et al [10] Tutwiler and Ryzlak [25] Wolf et al [31] a Values express EDs0 (25%) + SEM, calculated from dose-response relationships with 12 rats per dose group poglycaemic effect on the baseline glucose but also lowered the 'excess area' under the glucose concentration curve (Fig. 4).…”

Section: Dogs Streptozotocin-diabetic Pigs and Genetic-diabetic Micmentioning

confidence: 99%

Phenylalkyloxirane carboxylic acids, a new class of hypoglycaemic substances: Hypoglycaemic and hypoketonaemic effects of sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (B 807-27) in fasted animals

1982

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Summary.Phenylalkyloxirane carboxylic acids and esters are a new class of potent hypoglycaemic substances. Sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (B 807-27) produces a dosedependent hypoglycaemic effect when administered orally or intravenously to several fasted laboratory animals, i.e. rats (with and without adrenalectomy), guinea pigs, dogs, streptozotocin-treated diabetic pigs and db/db-mice. In addition, the substances have a more pronounced lowering effect on ketone bodies in the blood than any other known substance. The minimal dose for lowering blood glucose significantly in rats is 15 gmol/kg. The corresponding dose for a significant lowering of ketone bodies in the blood is < 2.4 lxmol/kg. Hence, the substance B 807-27 is approximately five times more potent than tolbutamide and 30 times more potent than the biguanide buformin with respect to lowering blood glucose levels. B 807-27 differs from the sulphonylureas in that it fails to stimulate insulin secretion. In contrast to the biguanides, the substance decreases rather than increases blood lactate concentration and blocks both fatty acid oxidation and gluconeogenesis. The therapeutic usefulness of these compounds in diabetic man remains to be elucidated.

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Biguanide (Experimenteller Teil)

Cited by 19 publications

References 285 publications

Metformin: historical overview

Metformin: historical overview

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

Phenylalkyloxirane carboxylic acids, a new class of hypoglycaemic substances: Hypoglycaemic and hypoketonaemic effects of sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (B 807-27) in fasted animals

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