The acute effects of insulin on the cardiorespiratory responses to hypoxia in streptozotocin-induced diabetic rats

Abstract

Aims: We examined whether or not streptozotocin (STZ)-induced diabetic rats, which have a lower heart rate (HR, beats min-1) than control rats, could maintain hypoxic ventilatory response. Methods: Twenty-six Wistar rats, which had been injected with STZ (60 mg kg-1, EXP) or vehicle (0.1 M citrate buffer, CONT) intraperitoneally at 9 weeks of age, had their cardiorespiratory responses to normoxia and 12% O2 examined after 5 weeks. Results: Compared with CONT rats, EXP rats had a higher blood glucose [24 ± 3 vs. 5 ± 1 (mean ± SD) mmol L-1], a lower body weight (320 ± 23 vs. 432 ± 24 g), lower HR (303 ± 49 vs. 380 ± 44 in normoxia, and 343 ± 56 vs. 443 ± 60 in hypoxia) and a lower mean arterial blood pressure (MAP) (89 ± 6 vs. 102 ± 10 mmHg in hypoxia). In contrast, both groups had similar values in ventilation (V̇E), V̇E-metabolic rate (MR) ratio and arterial blood gases (ABGs). In EXP rats, with an acute insulin supplement (i.v., 0.75 U h-1 for 1.5-2 h), not only blood glucose, but also HR, and MAP were normalized as those obtained in CONT rats, and V̇E in hypoxia further increased without affecting V̇E-MR ratio and ABGs. Such acute cardiorespiratory stimulating effects of insulin could not be obtained in non-diabetic rats (n = 7, 355 ± 24 g), in which euglycaemia (mean 6.4 mmol L-1) was maintained during the measurements. Conclusions: Our results suggest that, in STZ-induced diabetic rats: (1) ventilation is hardly suppressed by hyperglycaemia, (2) cardiorespiratory responses can be acutely stimulated by short insulin injection, and (3) the effects, including those through acute blood glucose normalization, are possibly specific for the diabetic impairments.