Since 1911 the problem of placental permeability to insulin has been studied sporadically. Carlson, Drennan, Orr and Jones (1, 2) observed that pregnant dogs failed to develop glycosuria after pancreatectomy and concluded that the fetus protected the mother against diabetes, presumably by diaplacental movement of some substance. Other investigators (3, 4), however, were unable to confirm these early studies. Results of work with goats (5), rabbits (6, 7) and mice (8) were variable and suggest that species differences exist in the placental permeability to insulin. By in vitro techniques, systems for the proteolytic inactivation of insulin have been demonstrated in the rat (9) and human placenta (10).This study was undertaken to investigate the role of the human placenta in the transfer and metabolism of insulin in vivo. It was assumed that the placenta handles insulin-I131 as it would unlabeled insulin. METHODTwenty-eight term-pregnant women, 14 to 41 years old, were chosen for this study without regard to parity. No diabetic patients were included. Except for two patients with mild pre-eclampsia (experiments 3 and 7), no complicating diseases were present. Four patients were delivered by elective repeat cesarean section (experiments 3, 7, 15, 16) with TCA due to losses of protein-bound radioactivity by adsorption to glass (10, 11). In subsequent experiments glass adsorption was minimized by using saline containing 0.5 per cent human serum albumin for the dilution of the labeled insulin.Several preparations of insulin-I.31 were analyzed by unidimensional descending chromatography on Munktell 20/150 filter paper (12) in butanol-acetic acid-water (3: 1: 4 or 8.5: 1: 7.5) after being supplemented with unlabeled carrier insulin, sodium iodide, L-monoiodotyrosine (MIT) and L-diodotyrosine (DIT). The iodinated carrier compounds were localized by staining with a solution of ceric sulfate-arsenious acid followed by aniline in acetone (13). Duplicate chromatograms were also sprayed with 0.1 per cent ninhydrin in acetone. The papers were cut into 1-to 2-cm segments and counted in a scintillation well counter. When detectable, the sum of the radioactivity migrating with the mobility of MIT and DIT was less than 1 per cent of the total radioactivity.
Rats, fasted 18 hours, were injected intraperitoneally with 2.85 or 3.0 gm/ kg of ethanol. Blood samples were obtained 1.5 and 4.5 hours later. The entire rat was ground and mixed. The ethanol concentration of blood and tissues was determined. The rate of metabolism was lower and the factor r higher when calculated from the declining blood values than when determined directly. The factor r did not bear a close relation to total body water or ether-extract. The rate of alcohol metabolism varied from animal to animal within the species despite efforts to maintain constant experimental conditions.
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