Effect of buformin on splanchnic carbohydrate and substrate metabolism in healthy man

The effect of buformin (100 mg b.i.d. for 5 days) on carbohydrate metabolism, both splanchnic glucose output (SGO) and net substrate exchange were studied in 6 healthy male volunteers in the basal state and following glucose ingestion (100 g). Control studies without buformin were also performed in 5 men. Splanchnic glucose and substrate exchange was determined by means of the hepatic venous catheter technique. SGO was 154 ± 18 (SEM) mg/min in the postabsorptive state and increased 33.3 ± 2.8 g above the basal level during the 150 min period following glucose ingestion. Buformin administration did not alter basal SGO (157 ± 26 mg/min), nor the splanchnic exchange of pyruvate, alanine, glycerol, OH-butyrate and acetoacetate. Splanchnic lactate balance was altered by buformin and net lactate output occurred. Following glucose ingestion the rise in splanchnic lactate output was increased, whereas no change in SGO ($\text{32.9 ± 3.5 g}\text{150 min}$) and splanchnic exchange of the other substrates was observed. The increase in arterial blood glucose concentration following oral glucose loading was reduced by buformin pretreatment (p < 0.0005). The insulin production rate (basal, 16 ± 2 mU/min; following oral glucose, $\text{13 ± 2 U}\text{150 min}$) as calculated from C-peptide release from the splanchnic area was unchanged by buformin. Except for a marked rise in splanchnic lactate production, buformin did not alter splanchnic carbohydrate metabolism after orally ingested glucose in healthy man. The diminished increase in arterial blood glucose concentration associated with unaltered insulin production suggests that buformin facilitates glucose utilization by peripheral tissues.