Treatment of reactive hypoglycemia with buformin. (1/2)

The therapeutic effect of short-term buformin (l-butylbiguanide) treatment was investigated in 12 patients with reactive hypoglycemia. Eleven of them were classified as having idiopathic reactive hypoglycemia, nine obese and two nonobese. None of these patients had a degree of hyperglycemia during glucose tolerance tests which would indicate diabetes mellitus. In one patient reactive hypoglycemia was related to chemical diabetes. The diagnosis of reactive hypoglycemia was established on the basis of patient's hypoglycemic reaction and low blood glucose levels during 6-hour oral glucose tolerance tests. The patient's received 200 mg of buformin daily for 7 days and its therapeutic effectiveness was assessed by repeat testing. Buformin treatment resulted in significant increase of blood glucose values between 180 and 360 min after oral glucose challenge and in considerable improvement of hypoglycemia in nine obese patients with idiopathic reactive hypoglycemia and in the patient with chemical diabetes. Buformin also significantly reduced maximal insulin response and incremental insulin areas. In two nonobese patients hypoglycemic reaction was deteriorated after buformin therapy.  (+info)

Buformin suppresses the expression of glyceraldehyde 3-phosphate dehydrogenase. (2/2)

The biguanides metformin and buformin, which are clinically used for diabetes mellitus, are known to improve resistance to insulin in patients. Biguanides were reported to cause lactic acidosis as a side effect. Since the mechanism of the side effect still remains obscure, we have examined genes whose expression changes by treating HepG2 cells with buformin in order to elucidate the mechanisms of the side effect. A subtraction cDNA library was constructed by the method of suppressive subtractive hybridization and the screening of the library was performed with cDNA probes prepared from HepG2 cells treated with or without buformin for 12 h. The expression of the gene and the protein obtained by the screening was monitored by real-time RT-PCR with specific primers and Western blotting with specific antibody. The amounts of ATP and NAD+ were determined with luciferase and alcohol dehydrogenase, respectively. We found that expression of the glyceraldehyde 3-phosphate dehydrogenase (GAPD) gene was suppressed by treating HepG2 cells with 0.25 mM buformin for 12 h as a result of the library screening. The decrease in the expression depended on the treatment period. The amount of GAPD protein also decreased simultaneously with the suppression of the gene expression by the treatment with buformin. The amount of ATP and NAD+ in the HepG2 cells treated with buformin decreased to 10 and 20% of the control, respectively. These observations imply that the biguanide causes deactivation of the glycolytic pathway and subsequently the accumulation of pyruvate and NADH and a decrease in NAD+. Therefore, the reaction equilibrium catalyzed by lactate dehydrogenase leans towards lactate production and this may result in lactic acidosis.  (+info)