The aim of the present work was to study the effects of experimental changes in plasma free fatty acid (FFA) levels on basal insulin (I]~I) concentration and on fl cell response to IV glucose, tolbutamide or glucagon in man. Each of the 53 subjects tested was studied on two separate occasions: i) in the basal state; ii) after an experimental decrease or increase in plasma FFA levels induced, respectively, by administration of nicotinic acid or the combination of a fat meal and heparin. The lowering of plasma FFA resulted in a small but significant fall in basal insulin concentration and in a 30% decrease in II~I response whatever the insulinotropic agent used. On the other hand, experimental elevation of plasma FFA enhanced pancreatic response to glucose (-~ 178%) and tolbutamide (n a 58%), but did not alter significantly the Ii~I respons~ to glucagon. Both the increase and the decrease in FFA concentration resulted in a reduction in the rate of glucose assimilation.-These results provide arguments for a role of plasma FFA in the control of insulin secretion and of insulin sensitivity in l~an.

No abstract

Summary. Sodium fl-hydroxybutyrate was infused for 1.5 h in 8 normal subjects, at a constant rate of 5 mmoles/ kg/h. Equimolar amounts of sodium chloride were infused in 5 control subjects. --The induced hyperketonaemia provoked the following changes in peripheral blood : a fall in glycaemia (15 rag/100 ml) and in plasma NEFA concentration (50%) without concomitant modifications of insulin concentrations. These results indicate that the glucose and NEFA changes observed are not mediated by a pancreatic stimulation. Modifications des concentrations de glucose, d'acides gras libres, d'insuline et de corps cgtoniques darts le sang pendant des perfusions de fi-hydroxybutyrate de sodium chez l'hommeRdsum~. Les auteurs ont @tudi6 chez 8 sujets normaux les effets d'une perfusien de fl-hydroxy-butyrate de sodium (5 m mol/kg/h pendant 1.5 h) sur la concentration sanguine en glucose, en acides gras libres, en corps c6toniques et en insuline dans le sang' veineux pdriph6rique. Cinq sujets tdmoins ont dtg perfusds ~ l'aide de solution (~qui-molaires de NaC1. --L'hypercdtondmie provoque une chute de la glycdmie d'environ 15 rag/100 ml, une chute des NEFA atteignant 50~o, sans modifications concommitantes de l'insulindmie. Ces rdsultats plaident contre Fintervention d'une stimulation pancrgatique darts la chute de la glyc@mie et des NEFA. .~nderungen der Glucose-, 2'~FS-, Insulin-und Ketolc6rper-Konzentrationen unter einer 2Vatrium-fi-hydroxybutyrat-Infusion beim MenschenZusammenfassung. Natrium-fi-hydroxy-butyrat wurde 8 Normalpersonen w~hrend 1.5 Std bei konstanter Geschwindigkeit yon 5 mMol/kg/Std infundiert. 5 Kontrollpersonen erhielten /~quimolekulare Mengen einer KochsalzlSsung. --Die so bewirkte ErhShung der Ketok6rper-Spiegel fiihrte im peripheren Blur zu folgenden Veriinderungen: Absinken des Blutzuckers um 15 mg ~o, Abfall der Plasma-FFS auf die H~lfte ohne gleichzeitige _~nde-rung der Insulinspiegel. Diese Ergebnisse sprechen dafiir, dal3 die Anderung der Glucose-und FFS-Konzentrationen nicht durch eine Stimulierung des l)ankreas ausgelSst wird.

Coelomic fluid (n = 57), amniotic fluid (n = 61) and maternal serum (n = 81) were obtained from normal pregnancies between 7.7 and 13.9 weeks and assayed for total protein, alpha-fetoprotein (alpha FP), albumin and pre-albumin. The mean concentration of total protein in matched samples was 18 times higher in maternal serum than in the coelomic fluid and 54 times higher in the coelomic fluid than in amniotic fluid. The concentrations of total protein, albumin and pre-albumin decreased and that of alpha FP increased in maternal serum with advancing gestation. The yolk sac volume and the concentrations of total protein in the coelomic and amniotic fluids increased with gestational age. No difference was found for the crown-rump length, yolk sac volume and protein concentration in the coelomic fluid between two groups presenting with low and high maternal serum pre-albumin concentrations. Before 11 weeks gestation, significant correlation was only found between yolk sac volume and coelomic fluid concentration of pre-albumin as evaluated by both electrophoresis and immunonephelometry. These results suggest that during the first trimester of normal pregnancy, the placental metabolism and transfer rate of proteins is not directly influenced by the concentrations of protein in the maternal circulation and that the transfer of proteins through the amniotic membrane is limited. These results also indicate that during that period the secondary yolk sac may contribute to the protein content of the exocoelomic cavity, and that the embryo and its yolk sac and subsequently the fetus are the main source of the proteins present in the amniotic fluid.

AB S T RAC T Experiments were designed to compare the distribution of free and antibody-bound unlabeled insulin to the distribution of free and antibody-bound insulin-125I. The insulin antibody was incorporated in a specific immune precipitate similar to the one used by Hales and Randle for the radioimmune assay of insulin. Insulin which was not bound by the specific immune precipitate was measured by the immune hemolysis inhibition assay. This report contains evidence that the addition of the unlabeled insulin in the radioimmune assay results in relatively more insulin-125I which remains free and less bound by antibodies than is the case with the unlabeled insulin. Methods are described for the separation of an electrophoretically homogeneous iodoinsulin from samples of crude iodoinsulin with average incorporations of less than 0.2 atoms iodine per molecule. These purified iodoinsulin fractions have a markedly attenuated biological activity. Evidence is presented which supports the postulate that only a portion of the antibodies in guinea pig insulin antiserum are capable of effectively binding with purified iodoinsulin.

Exocoelomic and amniotic fluids were obtained by selective puncture under ultrasound guidance in normal human pregnancies between 5 and 13 weeks of gestation. Evaluation of the protein patterns in the exocoelomic fluid showed qualitative and quantitative changes with advancing gestation. During the second month of gestation, three electrophoretic bands were found with mobility compatible with albumin, alpha 1-globulin and beta-globulin and composed of at least eight proteins including: pre-albumin, albumin, alpha-fetoprotein (alpha-FP), alpha 1-protease inhibitor, haptoglobin, ceruloplasmin, transferrin and immunoglobulin-G, as revealed by immunoblotting. Protein patterns obtained between 9 and 13 weeks were comparable in exocoelomic fluid and in maternal serum except for the presence of alpha-FP in the alpha 1-globulin band. At the same gestational age, protein electrophoresis of amniotic fluid revealed four bands corresponding to albumin, alpha-FP, haptoglobin and transferrin. Creatinine levels were significantly lower (P less than 0.01) in amniotic fluid than in exocoelomic fluid, and alpha-FP levels were similar in both exocoelomic and amniotic fluids. These results suggest that the exocoelomic fluid is a transudate of the maternal serum except for the presence of high levels of alpha-FP, that amniotic and exocoelomic cavities are separated by a non-permeable membrane and that the secondary yolk sac plays an important role in early protein synthesis and transfer.

The interferon‐induced double‐stranded RNA‐activated (2′‐5′)oligo(adenylate) synthetase converts ATP into (2′‐5′)oligo(adenylate) [(2′‐5′)oligo(A)] and pyrophosphate. In turn, (2′‐5′)oligo(A) activates a latent endoribonuclease which cleaves single‐stranded RNA. (2′‐5′)Oligo(A) synthetase activity has been characterized in liver cells of normal and germ‐free rats. This enzyme is predominantly nuclear. After partial hepatectomy, (2′‐5′)oligo(A) synthetase activity decreased rapidly (after 10 h) and markedly to a minimum of 25% of the control after 20 h. This decrease was followed by a slow restoration of the activity. No such change was observed in sham‐operated animals. This important decrease of enzymatic activity occurred during the first few hours of liver regeneration (6–24 h). This period corresponds also to the prereplicative and replicative (18–24 h after hepatectomy) phases of DNA. Detailed kinetics indicated that the loss of (2′‐5′)oligo(A) synthetase activity preceded the onset of the incorporation of tritiated thymidine in DNA and was minimal when the rate of DNA synthesis was maximal. These results and those obtained in culture of cells in vitro are compatible with the hypothesis that the (2′‐5′)oligo(A) system participates in the negative control of cell proliferation.

schen der Verschlcchterung dcr Xonstante der Glucoseutilisationsrate und der Geschwindigkeit des Prozesses zeigt, unabhgngig vonder Menge des vorhandenen oder zugefiihrten Insulins. Diese Ergebnisse lassen vermuten, da~ die StoffwechselstSrung bei der menschlichen Fettsucht primer eher den Proze~ der Glueoseaufnahme selbst als die Insulinwirkung betrifft.