Although stress is suspected to play a role in the development of diabetes mellitus, no direct experimental evidence for involvement of the adrenal medullae in onset of the disease has yet been found. We recently observed that, in comparison with sham-operated rats, fewer adrenodemedullated rats become diabetic after an i.v. injection of streptozotocin (STZ); thus, the present study examined the role of the adrenal medullae in the development of experimental diabetes. Male Wistar rats were surgically adrenodemedullated (ADM) or sham-operated (SHAM). After a 3-week recovery period, they were injected with 40 mg STZ/kg freshly dissolved in citrate buffer or buffer alone. A 1-mL arterial blood sample was withdrawn 12 days later in previously cannulated animals; then the rats were killed and their pancreas was removed. The plasma glucose levels were lower in ADM rats injected with buffer alone than in their SHAM counterparts (7.7 +/- 0.1 vs. 8.5 +/- 0.1 mmol/L; p < 0.05). The glucose levels were higher (p < 0.001) in both groups of STZ-treated rats, with values 28% lower in ADM than in SHAM rats (14.7 +/- 1.6 vs. 18.8 +/- 1.2 mmol/L; p < 0.03). Whereas plasma insulin levels did not differ between ADM and SHAM rats injected with buffer alone (431 +/- 38 vs. 428 +/- 35 pmol/L; p > 0.05), they were diminished in SHAM animals injected with STZ (292 +/- 37 vs. 428 +/- 35 pmol/L; p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)