By intra-arterial postmortem staining of the pancreas with hematoxylin after the administration of nonradioactive microspheres to anesthetized unfasted rats, the following values (+/-SE) were obtained: mean single islet volume, 1.00 +/- 0.12 nl (median 0.32 +/- 0.04 nl, n = 14); pancreatic intensity of perfusion, 1.18 +/- 0.14 ml X min-1 X g-1 (n = 10); percentage of pancreatic flow to islets, 6 +/- 1% (n = 10); single islet blood flow, 20 +/- 3 ml X min-1 (n = 10); and islet perfusion, 19 +/- 3 ml X min-1 X g-1 (n = 10). Perfusion of islet tissue was calculated to be above average for very small islets and to decrease with increasing islet size to become below average for very large ones. Details of the distribution of the total islet flow to subpopulations of islets grouped according to single islet size are shown pictorially.

A simple instrument is described which measures the breaking strength of rat bones. The apparatus yields reproducible results and is suitable for use in measuring the strength of bones from both large and small animals. Diabetic rat femurs were more fragile and required less force to break in contrast to those from diabetic rats treated with insulin or normal rats. Daily insulin treatment significantly improved the bone cortical thickness and enhanced their capacity to withstand pressure, although these did not reach the level of the normal controls. The amount of force required to break the bone appears to be related to its cortical thickness and mass.

The question of the teratogenicity of lithium carbonate was tested in two inbred strains of mice that are susceptible to teratogens. Strains 129 and A/J mice were treated with varying dosages of lithium carbonate on day 8, 9, or 10, and strain A/J mice were sequentially treated on days 11, 12, and 13 of gestation. Another group of mice of strain 129 were given lithium carbonate in drinking water throughout pregnancy. Levels of lithium were determined in mouse serum (and in brain) of mothers and their offspring with the purpose of comparing equivalent values in mice and in man. A baseline dosage of 0.8 mg of lithium carbonate was chosen, since this dose produced a serum lithium level of 0.8 meq/L, which is comparable to values of patients treated for manic-depressive illness. This baseline dosage or 2 and 4 times this amount did not prove teratogenic in strain 129 mice. However, 5.0 mg (200 mg/kg), which is one-half the LD50 value, caused 41% malformations. The baseline dosage did not cause malformations in strain A/J when given on day 11, 12, or 13 of gestation. Lithium carbonate given in the drinking water to strain 129 mice throughout pregnancy at a concentration that produces serum levels in mice consistent with human values was deleterious. The data suggest that whole or part of total litters were eliminated. The few survivors were apparently normal. Our results suggest that 6 times the therapeutic serum lithium level in humans is teratogenic in mice, as tested by acute experiments. Chronic treatment with a quantity of lithium that produces a serum level equivalent to that of human values is toxic to whole or part of the litters of mice.

The possible cause(s) of impaired glucose tolerance in protein-calorie malnutrition was studied. The beta-cell mass was morphometrically determined and the sensitivity to alloxan was characterized in rats fed ad libitum a 4% protein diet, pair-fed or fed ad libitum a 20% protein diet. The percentage of beta-cells in the pancreas was neither affected by protein deficiency nor influenced by caloric intake. However, the diabetogenicity of alloxan was greatly reduced in protein-malnourished rats. This reduction in diabetogenicity by alloxan was partially reversed by feeding animals with sulfhydryl compound. These results suggest that decreased insulin secretion in protein malnutrition is not due to a reduction in beta-cell number.

Goosefish islets were homogenized in 0.25 M sucrose and separated into nuclear, mitochondrial + secretion granule, microsomal, and supernatant fractions. Eighty per cent of the cytochrome oxidase activity and 75 per cent of the bioassayed insulin activity were found in the mitochondrial + secretion granule fraction (6000 g for 10 minutes). The mitochondrial + secretion granule fraction was further subfractionated by centrifugation (2 hours at 100,000 g and 0°C) using a continuous linear density gradient 1.0–2.0 M sucrose). Eighteen to 20 subfractions were collected by piercing the bottom of the tube and collecting drops. The total protein was distributed into a bimodal curve consisting of a high density component, which contained 90 per cent of the insulin (secretion granules), and a lower density component, which contained the cytochrome oxidase activity (mitochondria).