John T. O'Brian

Endocrine and neurophysiologic responses of the pituitary to insulin-induced hypoglycemia: A review

Abstract Insulin-induced hypoglycemia normally evokes a physiologic hormonal response as the body attempts to maintain glucose homeostasis. Approximately 20 to 60 minutes following insulin administration, elevations in plasma concentrations of glucagon, epinephrine (Epi), norepinephrine (NEpi), cortisol, growth hormone (GH), and adrenocorticotrophic hormone (ACTH) are usually observed in response to acute hypoglycemia in normal subjects. 1–75 Therefore, one may test for selected deficiencies of hormonal secretory capacity in subjects with suspected endocrine dysfunction by inducing hypoglycemia with insulin administration. The insulin hypoglycemia (IH) test may be utilized in the evalution of patients with a variety of clinical endocrine disorders (Table 1). A review of the literature has yielded a total of 6,052 reported IH tests. In addition, we have conducted a retrospective analysis of 528 such procedures done at our institution between the years 1974 and 1984, in part previously reported. 59 Of all these tests, 4,916 procedures were performed in adults and 1,664 in children. This article represents an attempt to integrate these data, identifying not only the clinical usefulness of the IH test but also the physiology involved.

Enhanced phospholipase A2 activity in rat plasma, liver, and intestinal mucosa following endotoxin treatment: A possible explanation for the protective effect of indomethacin in endotoxic shock

Endotoxin administration in rats produced a significant increase in plasma, hepatic, and intestinal phospholipase A2 activity within three minutes after injection. The elevated phospholipase A2 activity seen in these tissues returned to normal levels six minutes after injection. The changes in phospholipase A2 activity were dose-dependent within the 0, 10, and 20 mg/kg range of treatment with Escherichia coli endotoxin. This increase in plasma, hepatic, and intestinal phospholipase A2 was abolished by prior treatment of the rats with 3 mg/kg indomethacin, a drug known to improve survival in endotoxic shock. The fact that the change in phospholipase A2 occurs soon after endotoxin administration and that the change in phospholipase is blocked by protective doses of indomethacin suggests that phospholipase A2 activation may be an important initial event in the lethal action of endotoxin, and that the protective effects of indomethacin may be directly related to inhibition of phospholipase A2 activity. Further, in vitro studies of the effects of indomethacin on hepatic phospholipase A2 activity showed that indomethacin significantly inhibited this enzyme. Indomethacin (25 mumol/L) produced 56% inhibition in phospholipase A2 activity and the apparent Ki for indomethacin was 9.2 mumol/L. Kinetic analysis using the Lineweaver-Burk method showed that the indomethacin inhibition was of the noncompetitive type.

“Bovine ketosis” in a nondiabetic postpartum woman

A 19-yr-old woman developed ketoacidosis 7 wk after the delivery of her first child. Despite breast feeding, she had been on a weight reduction diet resulting in a loss of 12 kg/body wt. With the development of a urinary tract infection, the patient became dehydrated and was found to be in ketoacidosis (arterial pH was 7.25 and PaCO2 was 17 mm Hg). The patient did not use alcohol and was nondiabetic. Therapy with adequate calories, intravenous fluids, and an appropriate antimicrobial agent resulted in prompt normalization of the laboratory abnormalities and resolution of the patients symptoms. The hypothesis is advanced that the postpartum status of the patient put her at particular risk for development of ketoacidosis and that this may represent the first reported episode of “bovine ketosis” in a human.