Respiratory inhibition and hypoglycemia by biguanides and decamethylenediguanidine☆
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Biguanides: Species with versatile therapeutic applications
2021, European Journal of Medicinal ChemistryCitation Excerpt :After this, various studies were carried out to understand the mode of action of biguanides [284]. Shapiro et al. synthesized a large set of alkyl, aryl, arylalkyl biguanide derivatives to obtain a potential hypoglycemic agent [285]. In arylalkyl derivatives, it was observed that increasing the alkyl chain length connecting aryl to biguanide, substitution of alkyl group on aryl ring diminished the hypoglycemic activity.
Adventures with insulin in the islets of langerhans
2011, Journal of Biological ChemistryCitation Excerpt :Unlike the sulfonylureas, they did not require a functioning pancreas to lower blood glucose, but instead they appeared to stimulate the glycolytic pathway, resulting in increased glucose uptake but associated with a buildup of lactate in the blood of treated animals. This suggested a possible “Pasteur effect” on aerobic metabolism, and indeed, I was soon able to obtain evidence, using an available Warburg apparatus in the laboratory, of an inhibitory effect of phenformin (phenylethylbiguanide (PEBG)) on tissue respiration that we traced to mitochondrial oxidative systems, most likely at the level of cytochrome oxidase (5). This kind of action seemed to correlate with clinical findings of mild malaise, decreased appetite, and weight loss among patients treated for longer periods with PEBG in the clinic.
The effects of phenformin on the transport and metabolism of sugars by the rat small intestine
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These investigations were supported by grants from the National Institute of Arthritis and Metabolic Diseases, Public Health Service.