Search PubMed⌕ Search

Biomedical subjects

H Mehnert

Publications and source records attributed to H Mehnert.

At least 181 records · Page 10Linked to original sources

Effect of phenformin on hepatic balances of gluconeogenic substrates in man.

The effect of a five day pretreatment with phenformin (3 X 50 mg daily) on hepatic metabolism was studied in six healthy volunteers. Arterial and hepatic venous concentrations of substrates and hepatic blood flow were estimated during a basal period and during a low-dose lactate infusion (0,03 mmol . kg-1 . min-1). The results have been compared with those obtained from untreated normal subjects in a previous study (16). During the baseline period arterial concentration of alanine and the hepatic venous concentration ratios of alanine: pyruvate and beta-hydroxybutyrate: acetoacetate were significantly increased with phenformin treatment, while the balances of carbon dioxide and glucose and the fractional extraction of alanine were decreased compared to the values obtained in untreated subjects. During lactate infusion mean arterial lactate concentration was significantly increased and hepatic lactate extraction was decreased compared to untreated persons under the same conditions. In the phenformin-treated group lactate infusion resulted in hepatic output of pyruvate and the hepatic glucose balance remained unchanged compared to baseline. Since the rate of hepatic blood flow was not increased during lactate infusion a significantly smaller glucose output and lactate uptake was obtained with phenformin. These findings support the present view that the hypoglycaemic effect of biguanides is due, at least in part, to inhibition of hepatic gluconeogenesis.

Adult↗

Antiketogenic action of fructose in man.

The effect of fructose infusion (10 gm. every five minutes as a bolus followed by 0.5 gm. per kilogram X hours) on arterial concentrations and hepatic balances of ketones was studied in four juvenile diabetics 24 hours after the withdrawal of insulin. Arterial and hepatic venous concentrations of beta-hydroxybutyrate, acetoacetate, free fatty acids, fructose, and oxygen were measured. Hepatic blood flow was also determined. At constant rates of splanchnic fructose extraction, an 82 per cent diminution of the arterial hepatic venous concentration difference of the ketones was observed but the arteriovenous difference of free fatty acis rose moderately. Since hepatic blood flow was only slightly increased (17 per cent) there was no doubt that total hepatic ketone body formation was reduced. The magnitude of this antiketogenic action became apparent from the continuous fall of the arterial ketone concentrations. Since splanchnic oxygen uptake rose 40 per cent, it is suggested that the antiketogenic effect of fructose was due not only to enhanced re-esterification but also to accelerated oxidation of free fatty acids.

Acetoacetates↗

[Substrate metabolism of muscles during the early postoperative period: the effect of glucose infusions].

Muscle substrate metabolism was studied by measuring arterial deep-venous substrate concentration differences across the forearm in metabolically healthy volunteers 3 h after abdominal surgery. Despite elevation of insulin levels following glucose infusion, no effect on muscular fractional extraction of glucose and no decrease of lactate and alanine production was found, whereas muscular lipolysis was inhibited to a normal extent and ketone utilization was reduced.

Abdomen↗

[The effect of combined therapy with buformin and dichloracetate on blood lactate concentrations in diabetics].

In animals, dichloroacetate (DCA) which activates pyruvate dehydrogenase has been shown to diminish increased blood lactate concentrations due to biguanide treatment. In 10 maturity onset diabetics, therefore, the effect of a combined therapy with buformin and DCA (200 mg b.i.d.) was studied on blood lactate concentrations and compared with an analogous pre- and postinvestigation period of 6 days with buformin treatment alone (100 mg b.i.d.). Mean blood glucose concentrations remained the same during all 3 investigation periods. Also, neither fasting nor postprandially significant differences were found in blood lactate and ketones. In association with a standardized ergometer test, however, the rise in blood lactate was significantly smaller (p less than 0.05) while the patients were on buformin plus DCA, compared to the periods when only buformin was given. Furthermore, less ketone bodies appeared to be utilized by the exercising muscle under the influence of the combined treatment (p less than 0.05). These results are in good agreement with animal studies and suggest that DCA might be as effective in decreasing enhanced blood lactate concentrations in biguanide treated man as in animals.

Acetates↗

[Lactic acidosis in diabetics on biguanides (author's transl)].

A systematic search for cases of lactic acidosis among diabetics on biguanides revealed ten during an eight-month period, while in the preceding ten years not a single case had been definitely diagnosed. This represents a prevelance of 1 in 2000 patients admitted to hospital. All ten were over 60 years old and had previously been treated for heart failure. Most of them had suffered from renal insufficiency for some time. There was no case of biguanide overdosage. Criteria for the diagnosis of lactic acidosis are lactic concentration in blood averaging 18.4 mmol/l and a low pH, averaging 6.9. Serum-biguanide concentration (measured by radioimmuno-assay) was markedly increased. Most of the patients were in circulatory shock on admission or soon after and all of them had a history of gastro-intestinal complaints. Despite intensive treatment with insulin and glucose and careful correction of the acidosis with bicarbonate four of the ten patients died.

Biguanides↗