6-Amnionicotinamide (6-AN) as a diabetogenic agent. In vitro and in vivo studies in the rat.
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Biomedical subjects
Publications and source records attributed to J Steinke.
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Pancreases were obtained from five human fetuses 12 to 16 weeks old. The islets of Langerhans were isolated with collagenase, and then incubated with buffer, glucose, tolbutamide, or glucagon added to the medium. The insulin released into the medium was measured by immunoassay. Glucagon produced the only significant increase above base line; glucose and tolbutamide failed to enhance secretion of insulin. The data suggest that isolated human fetal islets of this gestational age develop responsiveness to glucagon earlier than to glucose or tolbutamide.
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In vitro metabolism of glucose-1-(14)C by adipose tissue into (14)CO(2) and total (14)C lipids in rat and man was compared employing both adipose tissue segments and isolated fat cells prepared from the same donor. In the rat, the basal glucose metabolism and response to insulin decreased with increasing body weight for both adipose tissue segments and isolated cells. Regardless of age, the isolated cells exhibited a persistently higher metabolic activity. Of the parameters selected, conversion to CO(2) was more pronounced than that to lipid.In contrast to the rat, in man adipose tissue segments were more active than isolated cells. In four subjects, the effect of 6, 50, and 400 muU/ml of insulin was analyzed on conversion of glucose-1-carbon to CO(2), long chain fatty acids, and glycerides by adipose tissue segments only. In 17 subjects, glucose oxidation and lipid synthesis by adipose tissue segments and isolated fat cells were measured and showed a definite response to physiological doses of crystalline pork insulin. There was, however, an age dependency, and consistent effects were obtained with 6 muU/ml in children and 50 muU/ml in adults. The responsiveness of human adipose tissue to exogenous insulin in concentrations comparable to those detected in blood reemphasizes the importance of adipose tissue as a major site for fatty acid synthesis.
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