Renal diabetes. Apropos of 103 cases

Three main concepts came out of this prospective study of 103 cases (51 girls and 52 boys) of renal diabetes followed up from 1955 to 1975 and reviewed in 1984: contrary to what is still sometimes written, renal diabetes does not evolve to diabetes mellitus; renal diabetes does not seem to progress over the years; the mode of genetic transmission, when present, which is rare, is obscure but it seems to occur in a recessive rather than a dominant fashion.     

Whole body de novo amino acid synthesis in type I (insulin-dependent) diabetes studied with stable isotope-labeled leucine, alanine, and glycine

Dynamic aspects of whole body alanine and glycine metabolism have been explored in insulin-dependent (type I) diabetic subjects. Using a primed, continuous intravenous (i.v.) infusion of [2H3]alanine and [15N]glycine given simultaneously with [1-13C]leucine, whole body alanine and glycine fluxes and their rates of de novo synthesis were measured in 6 diabetic young men. Subjects were studied in the postabsorptive state, after blood glucose was clamped overnight at 15.2 +/- 0.3 mM, and then, on the following night, at 5.9 +/- 0.2 mM (insulin infusion rates of 0.24 +/- 0.09 and 1.65 +/- 0.20 U/h, respectively). In the normoglycemic state, leucine, alanine, and glycine fluxes averaged 88 +/- 4, 378 +/- 39, and 155 +/- 8 mumol X kg-1 X h-1, respectively. Based on the leucine flux, alanine and glycine de novo synthesis rates were 264 +/- 36 and 67 +/- 8 mumol X kg-1 X h-1. In the hyperglycemic state, leucine flux increased 23% (P less than 0.01), alanine flux rose slightly (+5%) but significantly (P less than 0.05), while alanine de novo synthesis and glycine flux remained unchanged and glycine de novo synthesis decreased by 33% (P less than 0.001). These results show that small alterations in peripheral alanine inflow in the hyperglycemic state reflect increased proteolysis and suggest that increased circulating plasma glucose does not contribute to de novo alanine synthesis in the absence of adequate insulin effect and/or augmented glucose tissue uptake. These observations also reveal the importance of insulin in the maintenance of whole body leucine economy, since a lower rate of insulin administration was associated with an increased rate of leucine oxidation.     

The cis-regulatory sequences required for expression of the Drosophila melanogaster adult cuticle gene ACP65A

Post-embryonic development in insects requires successive molts. Molts are triggered by ecdysteroids, and the nature of the molt (larval, pupal or adult) is determined by juvenile hormones. The genes encoding cuticle proteins are targets of both classes of hormones, and therefore are interesting models to study hormone action at the molecular level. The Drosophila ACP65A cuticle gene is expressed exclusively during the synthesis of the adult exoskeleton, in epidermal domains synthesising flexible cuticle. We have examined the cis -regulatory sequences of ACP65A using phylogenetic comparisons and functional analysis, and find that only about 180 bp are essential, including an 81 bp intron. The restriction of ACP65A expression appears to depend on a strong repression mechanism.     

Excess of maternal HLA-DR3 antigens in HLA DR3,4 positive Type 1 (insulin-dependent) diabetic patients

Summary The susceptibility determinants of Type 1 (insulin-dependent) diabetes mellitus are known to be associated with both HLA-DR3 and DR4. In our study we wished to determine if the parental origin of these antigens could influence susceptibility to the disease. We analysed the inheritance of DR3 and DR4 haplotypes from the father or mother (DR3p, DR4p, DR3m and DR4m, respectively), in the index cases and in the affected and non-affected siblings of 246 diabetic simplex and 41 multiplex families without affected parents. An independent series of 80 multiplex families (GAW 5) was also studied. Among the DR3,4 positive index cases and affected siblings, the paternal and maternal DR3 and DR4 antigens were not distributed randomly: 62% and 72%, respectively, had received DR4 from their father and DR3 from their mother (DR4p/DR3m), while only 38% and 28%, respectively, had received a paternal DR3 together with a maternal DR4 (DR3p/DR4m). This differed significantly from the 50% expected ratio (p<0.01) and was not observed in unaffected siblings. No excess of maternal DR3 in the absence of DR4 and no excess of paternal DR4 in the absence of DR3 were observed. The finding suggests that some maternal DR3 related event (presumably during pregnancy) might play an enhancing role in the pathogenesis of Type 1 diabetes. It also implies that siblings with both DR4p and DR3m have a significantly higher risk for disease than those with DR3p and DR4m.     

L'Insulinémie dans la période d'installation du diabète infantile et juvénile

Résumé Chez 45 jeunes diabétiques au début de l'évolution de leur maladie et non encore soumis á l'insulinothérapie nous avons dosé l'insuline plasmatique au cours d'une ou plusieurs épreuves d'hyperglycémie provoquée par voie buccale. — Les résultats montrent: dans tous les cas et dès le début une insuffisance partielle ou complète de la sécrétion insulinique; une assez bonne correspondance entre la réponse insulinique et l'état clinique et biologique des malades. Dans les cas d'acidose grave, l'insulinémie est nulle. La réponse insulinique est nulle ou très abaissée dans les formes accompagnées de cétonurie. Chez les diabétiques non cétosiques, nous avons trouvé en général une réponse insulinique décelable mais inférieure à celle des sujets normaux en dépit d'une hyperglycémie très importante. Dans ces cas, nous avons distingué deux modalités principales de la sécrétion d'insuline sous surcharge 1. une élévation lente et tardive 2. une élévation progressive suivie d'un effondrement secondaire malgré une montée considérable de la glycémie.

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Insulinaemia during the manifestation period of infantile and juvenile diabetes

Summary Plasma-insulin levels during oral glucose-tolerance tests have been measured in 45 young diabetics at the beginning of their disease, and who were not yet under insulin therapy. — The results were: a partial or total deficiency of insulin secretion in all cases; a relationship between the poststimulatory insulin levels and the clinical and biochemical status of the patients. In cases of severe acidosis no insulin was detected. Insulin response was absent or very low in cases accompanied by ketonuria. In the non-ketotic diabetics we generally found an insulin response, but it was less than that of healthy controls in spite of marked hyperglycaemia. In these cases we distinguished two principal modes of insulin release: 1. slow and late increase, 2. initial increase followed by secondary collapse in spite of considerably high glucose levels.

Attachée de Recherches au CNRS.