The insulin response to an oral glucose load (100 gm.) in 127 patients with a previous myocardial infarction (MI) (six months to one year) and in 65 patients with surgically treated or arteriographically identified peripheral vascular disease (PVD) was compared with that of 89 controls after matching the three collectives for age, glucose tolerance, and per cent ideal body weight (% IBW). The insulin response was of greater magnitude in MI and PVD groups than in respective control groups also in the absence of hyperglycemia, hypertriglyceridemia, and obesity. This finding suggests that hyperinsulinism may represent an early metabolic alteration associated with the development of MI and PVD. The insulin secretion pattern was prevalently of the delayed type in association with impaired glucose tolerance and with hypertriglyceridemia but not with overweight. Correlations between serum insulin, triglyceride (TG) levels, and % IBW were also investigated. We found a strong correlation (p less than 0.001) between stimulated insulin levels and % IBW in MI patients and none in PVD patients; conversely, the correlation between serum insulin and TG levels was very high (p less than 0.001) in PVD patients and only weak (p less than 0.05) in MI patients. No correlation was found between cholesterol (CH) levels and any of the other parameters studied. According to these results, it seems likely that hyperinsulinism plays a major role as a closely associated factor to obesity in those subjects who develop an MI, whereas in PVD patients the raised insulin levels may favor lipid accumulation in the arterial intima and accelerate the progress of atherosclerosis.

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Cyclosporine A (15,30 or 50 mg/kg day) or olive oil (30 mg/kg day) were administered orally to 32 male Sprague-Dawley rats for 12 or 24 days, or withdrawn for 24 days following 24 days of treatment. The specific activity of a lysosomal marker enzyme N-acetyl-β-D-glucosaminidase was determined fluorometrically in single nephron segments microdissected from lyophilized kidney sections of these animals and of an additional 2 normal rats. The segments were classified according to their normal or reduced succinate dehydrogenase activity as detected in stained adjacent sections. In addition, urine specimens collected after 12, 24, 36, and 48 days of the experiment were tested for N-acetyl-β-D-glucosaminidase activity. After treatment with cyclosporine A, changes in the activities of N-acetyl-β-D-glucosaminidase were found only in the proximal tubules. In the convoluted segments with normal succinate dehydrogenase activity, the activity of N-acetyl-β-D-glucosaminidase was 138-163%, and in those with reduced succinate dehydrogenase activity, it was unchanged or 66-83% of the control values. In the straight segments with reduced succinate dehydrogenase activity, the activity of N-acetyl-β-D-glucosaminidase increased gradually along the medullary rays (122-214%) to the outer stripe of the outer medulla (178-263%) in comparison to the control values. In the urine specimens, the activity of N-acetyl-β-D-glucosaminidase was increased to 148-152%. These tubular and urinary changes were similar for each dosage and treatment period. After withdrawal of cyclosporine A they were not present. The variety of alterations occurring within the lysosomes along the proximal tubules of cyclosporine-A-treated rats implies the convoluted part as the site of increased release of N-acetyl-β-D-glucosaminidase into the urine.