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To investigate whether prostaglandins (PGs) play a role in the regulation of insulin secretion during starvation, we have studied the effects of two inhibitors of PG synthesis, indomethacin (INDO) and acetylsalicylic acid (ASA), on plasma insulin during a 72-h fast. Five lean males and six obese females were given 200 mg INDO daily throughout a 72-h fast during which plasma glucose was maintained at normal postabsorptive levels by a continuous infusion of glucose. In addition, four obese females were treated with 3 g ASA in a similar protocol. Another six lean males and six obese females served as a control group, receiving only iv glucose during the fast. In both the lean and obese control subjects, a significant decrease in plasma insulin was noted by 72 h (lean, 53 +/- 8% of basal insulin; obese, 69 +/- 6%; P less than 0.02). By contrast, aspirin and INDO administration prevented the decline in plasma insulin in both lean (INDO, 92 +/- 5%) and obese (INDO, 109 +/- 11%; ASA, 111 +/- 17%) subjects. These data suggest that endogenous PG production may be a controlling factor in insulin secretion during starvation.

The effect of aspirin on glucose and insulin metabolism was examined with the hyperglycemic clamp technique in 8 normal volunteers. When the plasma glucose concentration was acutely raised and maintained at 125 mg/dl above the basal level after treatment with aspirin (3 g daily for 3 days), acute (0-10 min) and sustained (20-120 min) insulin release were 70% and 45% greater than before treatment. Despite the increased plasma insulin level, the glucose infusion rate remained unchanged (8 +/- 0.9 to 9.1 +/- 1.2 mg/kg X min). Consequently, the ratio of the glucose infusion rate to the plasma insulin level, an index of tissue sensitivity to endogenous insulin, decreased by 30%, indicative of impaired insulin action. Aspirin did not alter fasting levels of FFA. When ibuprofen, another prostaglandin synthesis inhibitor, was given to 10 normal volunteers, only an effect on acute insulin release could be demonstrated. These results demonstrate that aspirin not only enhances beta-cell sensitivity to glucose, but also impairs glucose metabolism in insulin-sensitive tissues. It is not clear whether these effects are related to aspirin's ability to inhibit prostaglandin synthesis.

We have evaluated a commercially available, direct, solid-phase radioimmunoassay kit for progesterone determination in serum or plasma. The assay is precise, within-run precision (CV) in the clinically significant ranges being 2.5 to 5.2%, between-run 5.5 to 5.8%. Mean analytical recovery of different concentrations of progesterone added to serum was 99.7% (range 95.3 to 102.7%). Fourteen closely related steroids showed no cross reactivity. The minimum detection limit was 0.5 microgram/L. Luteal-phase progesterone concentrations in serum were increased (greater than 3 micrograms/L) in 19 normal ovulatory menstrual cycles and decreased (less than 1.5 micrograms/L) in two nonovulatory cycles. We found this direct assay for progesterone to be analytically and clinically sound, and useful for assessing luteal-phase function.

To study the effect of physiological increments in plasma secretin concentrations on basal and glucose-stimulated insulin release, bolus iv glucose injections (5 g) were given to normal weight volunteers (less than 108% ideal BW) before, during, and 30 min after a secretin infusion at a rate of 0.125 U/kg.h, raising mean plasma immunoreactive secretin to 35.5 +/- 8.3 pg/ml. Acute insulin responses to glucose were unaffected during or after the secretin infusion. Furthermore, when plasma glucose was elevated to postprandial levels (128--165 mg/dl), a similar secretin infusion also failed to alter acute insulin responses. In addition, no changes in basal glucose or insulin levels were found when endogenous secretin concentrations were increased by intraduodenal acid infusion. Thus, increases in plasma secretin to concentrations seen in the postprandial state fail to alter acute insulin secretion. It is unlikely that secretin plays any role in the intestinal stimulation of insulin secretion.

The usefulness of measurements of urinary C-peptide excretion in indirectly assessing integrated insulin secretion during starvation was studied in eight obese subjects during a 72-h fast. Blood and urine samples were collected at 12-h intervals for measurement of insulin and C-peptide immunoreactivity. After 60 h, serum insulin and plasma C-peptide levels declined 47% and 37%, respectively, and the values were highly correlated (r = 0.8; P less than 0.001). By 72 h, urinary C-peptide excretion had declined to 70% of the level in the first 12-h period. The urinary clearance of C-peptide was not altered by starvation. A highly significant correlation was found between urinary C-peptide and C-peptide secretory rate (P less than 0.001). The molar ratio of plasma C-peptide to insulin remained constant during the fasting period. These data indicate that basal insulin secretion can be added to the list of physiological conditions in which beta-cell secretion can be effectively evaluated by urinary C-peptide measurement.

We present here the first performance evaluation of a new direct method for free thyroxin (T4) in serum by radioimmunoassay, with use of coated tubes and a radiolabeled T4 analog (Diagnostic Products Corp.). The assay is precise and robust: within-run imprecision (CV), 3.1-6.6%; between-run imprecision, 4.0-7.9%; no demonstrable variation between technologists irrespective of experience with the method. No outliers were observed when we compared the free T4 results with serum total T4. Reference values are reported for a total of 1243 euthyroid subjects; there was no significant age effect on serum free T4 in women 26 to 72 years old. The biological variation was about +/- 35% of the mean (2 SD). Free T4 results are the same for serum and plasma. The assay performs well in hypothyroidism and hyperthyroidism, and distinguishes individuals with thyroid disease from normal individuals. Free T4 values in women taking oral contraceptives are normal. Depressed results were often observed in acute nonthyroidal illness and continuing pregnancy. These results were directly comparable with those of another commercial direct radiolabeled-T4 analog kit for free T4.

Infusion of prostaglandin E2 (PGE2) has been previously shown to inhibit acute insulin release and cause glucose intolerance. The present studies were undertaken to assess the effects of PGE2 on 1) pancreatic beta-cell sensitivity to glucose, 2) glucose tolerance, 3) tissue sensitivity to insulin, 4) glucose production and clearance, and 5) plasma catecholamine, glucagon, and FFA levels. Six healthy adult subjects were studied with the hyperglycemic clamp technique (plasma glucose 125 mg/dl above basal for 2 h) before and 30 min after the start of a PGE2 infusion (10 micrograms/min). Plasma epinephrine, norepinephrine, and FFA were measured during the PGE2 infusion. In additional experiments, glucose production and utilization were measured isotopically ([3-3H]glucose) during PGE2 infusion. PG infusion diminished, but not significantly, acute insulin release (0-10 min preinfusion, 172 +/- 36; postinfusion, 148 +/- 45 microunits/ml . 10 min). Late insulin release (20-120 min) was unchanged. A significant decline occurred in the amount of glucose metabolized from 9 +/- 1.1 to 7.2 +/- 1 mg/kg . min. During the initial 30 min of PGE2 infusion, plasma FFA increased by 26 +/- 6% (P less than 0.025). Plasma epinephrine and norepinephrine rose from 40 +/- 6 to 104 +/- 24 pg/ml (P less than 0.05) and 204 +/- 17 to 440 +/- 30 pg/ml (P less than 0.01), respectively. PGE2 produced a prompt 30% rise in glucose output, which declined to basal levels by 60 min. Glucose clearance decreased transiently at 45 min by 23%. We conclude that the effects on glucose homeostasis noted during PGE2 infusion occur in the face of heightened adrenergic activity. These metabolic responses closely resemble adrenergically induced changes in glucose homeostasis. As such, before any metabolic effects can be attributed directly to infused PGE2, any metabolic effects can be attributed directly to infused PGE2, the role of concomitant catecholamine release must be considered.