To evaluate the role of calcitriol on insulin secretion in uraemia, nine patients on maintenance haemodialysis, never treated with vitamin D nor with calcium-channel blockers, were studied. Baseline glucose, insulin, C peptide, calcium, intact PTH, and calcitriol serum values were measured, and after an oral load of 75 g glucose, insulin and C peptide were also determined at 15, 30, 45, 60, and 120 min. Following 14 days of treatment with oral calcitriol (0.5 microgram/day), the same study protocol was applied. Serum calcitriol values, which were low as expected, increased after therapy, but did not reach the values observed in healthy controls. Despite no change in total serum calcium, intact PTH values decreased significantly (182 vs 88.3 ng/ml, P less than 0.003). Baseline serum insulin was significantly increased after calcitriol (7.5 vs 35 microU/ml, P less than 0.001). Similarly, an enhancement in insulin secretion following calcitriol was observed at 15 min (34 vs 70, P less than 0.01) and 30 min (57 vs 96 microU/ml, P less than 0.01). Computation of the total area under the curve confirmed these results. Changes in C peptide profile paralleled those described for insulin. These data confirm that vitamin D modulates pancreatic beta-cell secretion and suggest that calcitriol may regulate insulin release in uraemic patients.

ATPASE activities during development have been studied in rat brain (SAMSON and QuI", 1967), in nerve-ending particle fractions from rat brain (ABDEL-LATIF, BRODY and RAMAHI, 1967) and in the cerebral cortex of the kitten (HUTTENLOCHER and RAWSON, 1968), as well as in preparations of synaptosomes and microsomes of rat brain (ABDEL-LATIF, SMITH and ELLINGTON, 1970). In a previous which neurons abound. Finally, we again emphasize that the measurements of ATPase made on neuronal perikaryal preparations exclude ATPase associated with the neuronal processes and with the synaptic membranes shown by JOHNSON and SELLINGER (1971) to be virtually absent from these preparations.

Transbilayer diffusion of Mn2+ ions occurred in liposomes formed from dipalmitoyl-phosphatidylcholine or egg-yolk phosphatidylcholine and egg-yolk phosphatidate (molar ratio 2:1) containing DNA and DNase I within their aqueous compartments. Cation diffusion was demonstrated by the hydrolytic activity of DNase I, activated by the Mn2+ ions that diffused into the vesicles, and this was confirmed by light scattering. Phosphatidate, a cone-shaped lipid which has been synthesized under simulated prebiotic conditions, was necessary for cation diffusion across the liposome membranes. Such liposomes represent a simple precellular system that interchanges cations with the surroundings and provides a microenvironment for enzymatic reactions, as evidenced by the hydrolysis of DNA by DNase I inside these closed lipid compartments.

The hydrolysis of p-nitrophenyl-2-acetamido-2-deoxy-fi-~-gluco-(I) and 8-Dgalacto-pyranoside (11) and of p-nitrophenyl-a-D-mannopyranoside (111) by neuronal cell bodies and glial cells isolated from the cerebral cortex of 18-day-old or adult rats was found to be equally efficient, with relative ratios of hydrolysis for I, I1 and I11 of approximately 10: 1 : 0 5 in both cell types and at both ages. Homogenatesoftheneuronal cell bodies obtained from cerebral cortices of 3-, 8-, 12-, 18-and 32-day-old rats were subjected to differential centrifugation and the subcellular localization of N-acetyl-fi-o-ghcosaminidase (EC 3.2.1.30) bydrolysing (I)] was compared to that of the mitochondrial marker, succinate-INToxidoreductase (EC 1.3.99.1). A fraction in which N-acetyl-B-D-ghcosaminidase exhibited maximal specific activity could be isolated at all ages, an observation indicating that the potential for active hydrolytic performance is incorporated into the neuronal lysosome very early post-natally. The specific activities of N-acetyl-fi-D-glucosaminidase and succinate-INT-oxidoreductase reached their respective maxima at widely different times postnatally: at 10-12 days for the mitochondrial enzyme and at about 18 days for the glycosidase, a difference suggesting that in the cortical neuron lysosomes and mitochondria develop out of step. The mitochondrial, lysosomal and microsomal fractions obtained by differential centrifugation were subjected to equilibrium density centrifugation and the presence of two populations of N-acetyl-fi-D-glucosaminidase-bearing particles was demonstrated. Although their presence was readily apparent in the neurons from 8-and 12-day old brains, it was difficult to discern their presence in the neurons from the 3-and the 18-day-old brains. In 8-day-old brains gradient fractions obtained from neurons containing N-acetyl-P-Dglucosaminidase of a specific activity up to %fold higher than that of the enzyme in the original neuronal homogenate were examined by electron microscopy and the concentration of numerous lysosomes and derivative bodies in these fractions was verified. Our present study demonstrates the capability of the immature and developing neuron to tightly couple the pace of its degradative processes to that of its highly efficient and highly selective synthetic activities. acetylaminodeoxyglucohydrolase) is localized in the lysosomes of the cerebral cortex of the rat (SELLINGER, RUCKER and DE BALBIAN VERSTER, 1964) and the guinea pig (BOSMANN and HEMSWORTH, 1970), as well as in the lysosomes of several other anatomical areas of the rat brain (SELLINGER and HIAIT, 1968; SELLINGER and NORDRUM, 1969; SELLINGER, NORDRUM and IDOYAGA-VAKGAS, 1971b). TALLMAN, BRADY and SUZUKI (1971) recently demonstrated the lysosomal localization of this hydrolase in

The effects of L-leucine, D-leucine, and L-isoleucine upon the secretion of glucagon and insulin were investigated using the isolated, perfused rat pancreas. All experiments were conducted in the presence of 5.6 mM D-glucose. Ten-minute perfusions of 2, 5, and 10 mM L-leucine induced the release of glucagon and insulin in a dose-related manner. The removal of L-leucine was followed by renewed release of insulin ("off-response") but not of glucagon. The magnitude of the off-response was greater when L-leucine was perfused over longer periods. L-Isoleucine evoked the release of both glucagon and insulin. When L-leucine was administered during perfusion of L-isoleucine, L-leucine-induced release of glucagon was inhibited, that of insulin was augmented, and the insulin off-response prevailed. When the perfusion of L-leucine immediately preceded that of L-isoleucine, L-isoleucine-induced release of glucagon was abolished and that of insulin was augmented. D-Leucine evoked the release of glucagon but not of insulin, and no off-response occurred. When the perfusion of D-leucine followed that of L-leucine, D-leucine-induced glucagon release was inhibited; the insulin off-response to L-leucine was not altered. We reached the following conclusions. 1) Glucagon release induced by L-leucine, D-leucine, or L-isoleucine is likely to be related to the occupancy by these analogous amino acids of transport and/or receptor sites which they share. 2) The insulin off response to L-leucine seems to be evoked by events which take place during the period of administration of L-leucine; these events are not likely to be the release of insulin that occurs during perfusion of L-leucine or the transport of L-leucine into or out of the beta cell. 3) Structurally or chemically similar compounds which are secretagogues both for glucagon and insulin affect the release of these hormones in different ways; these differences are likely to be due to dissimilar mechanisms governing the secretion of the two hormones.