Jon H. Levine

Clinical teaching for medical residents: Roles, techniques and programs

Clinical Teaching for Medical Residents: Roles, Techniques and Programs (Springer Series on Medical Education, Vol. 10). Edited by Janine C. Edwards and Robert L. Marier, 1988, New York: Springer Publishing Company,

Effect of Streptozotocin-induced Diabetes on Renal Ornithine Decarboxylase Activity

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Stimulation of hepatic and renal ornithine decarboxylase activity by selected amino acids

The effects of streptozotocin(SZ)-induced diabetes on renal ornithine decarboxylase (ODC) activity, the rate-limiting enzyme in polyamine biosynthesis, were studied. Sixteen hours after the injection of SZ, renal ODC activity increased 50% above that of the vehicle-injected controls. The maximum increase in activity—600%—was observed from 24 to 72 h after SZ. Within a week, ODC activity fell below control levels and remained suppressed during a 3 wk follow-up period. Insulin treatment within 10 h of the SZ injection prevented the increase of ODC activity; however, insulin given after enzyme activity had increased did not restore ODC activity to control levels. The early increase of ODC activity occurred in the presence of mild hyperglycemia without ketosis or hyperglucagonemia, but the levels were much higher in severely diabetic animals. Adrenalectomy, performed before the initial increase in enzyme activity, prevented the subsequent increase in diabetic animals; however, when adrenalectomy was performed after the enzyme had increased, enzyme activity did not normalize.

Is Cyclic Amp the Regulator of Hepatic Ornithine Decarboxylase Activity

The activity of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, increases after a protein meal. The effect of amino acid mixtures on hepatic and renal ODC activity and polyamine content was studied in postabsorptive and 72-hour fasted rats. Fasting decreased ODC activity in liver and in kidney by approximately 50%. Hepatic ODC activity increased tenfold 4 hours after intraperitoneal injection of either 1 g/kg of a synthetic mixture of 17 amino acids or of casein hydrolysate to fed rats and about 20-fold in fasted rats. Renal ODC activity increased four- and tenfold respectively. A mixture of glutamate, aspartate, and alanine at concentrations given in the hydrolysate reproduced the full amino acid effect. No amino acid was effective when given alone, nor were mixtures of the other amino acid constituents of the hydrolysate. Glutamate + alanine was ineffective as were glucose or various combinations of arginine, ornithine, aspartate and NH3. Ornithine + glutamate or aspartate + glutamate were active but stimulated less than aspartate + glutamate + alanine. Hepatic and renal putrescine content increased in parallel with ODC activity. The data suggest that specific amino acids possess the full ODC-stimulating capability of a high quality protein and that polyamine synthesis is linked to urea cycle activity.

Prolactin‐secreting adenoma as part of the multiple endocrine neoplasia—type I (MEN‐I) syndrome

The role of cyclic AMP in the regulation of hepatic ornithine decarboxylase (ODC) activity in the rat was studied in the whole animal and in the perfused organ. Dibutyryl cyclic AMP or butyrate given to intact rats increased ODC activity; this increase was abolished by hypophysectomy 1 h prior to administering ether compound. Administration of 1 mg 1-methyl-3-isobutylxanthine (MIX) to intact rats increased ODC activity within 4 hours whereas hypophysectomy 1 h before treatment prevented this increase. No change in hepatic cyclic AMP content was seen in either intact or hypophysectomized rats following MIX. Perfusion with 0.5 mM dibutyryl cyclic AMP decreased ODC activity in isolated livers whereas perfusion with 0.5 mM 8-bromocyclic GMP produced a small increase in ODC activity. These data suggest that the effect of dibutyryl cyclic AMP in intact animals may be a property of the butyrate and that this action as well as the action of MIX may be mediated through the permissive effect of pituitary and/or adrenal hormones. The normal hepatocyte does not increase its ornithine decarboxylase activity after direct exposure to dibutyryl cyclic AMP.

Altered platelet function in diabetes mellitus.

Two patients presented with the galactorrhea‐amenorrhea syndrome. One patient had previously had parathyroid hyperplasia and the other an insulinoma. Preoperative evaluation of each patient revealed hyperprolactinemia and radiological evidence of an abnormal sella turcica. Pituitary adenomas were identified and removed at surgery. Immunostaining techniques confirmed the presence of prolactin‐containing cells in both tumors. We propose that prolactin‐secreting tumors be considered as part of the MEN‐I syndrome, and that patients presenting with the galactorrhea‐amenorrhea syndrome be screened and followed sequentially for evidence of other endocrine neoplasia.