Endocrine Abstracts

Hypoglycaemia is an almost unavoidable consequence of iatrogenic insulin therapy in type 1 diabetes. Recurrent hypoglycaemia (RH) results in suppression of normal counter-regulatory hormonal and physiological responses (CRR) to future episodes increasing the risk of severe hypoglycaemia. The mechanisms responsible for this phenomenon remain unclear but may reflect changes in critical hypothalamic glucose sensing neurons (GSN). We set out to indirectly test the hypothesis that hypothalamic GSN ‘habituate’ to RH and that introduction of a novel stimulus, acute high-intensity (HI) exercise, could restore hypothalamic CRRs through a process of ‘dis-habituation’.

Male Sprague–Dawley rats (250–300 g; n=8–12/group) were exposed to RH (1 U/kg insulin i.p.; three times per week for 4 weeks or saline control). Subsequently, animals were divided into three groups: i) control, ii) low-intensity exercise (LI: total 25 min: 5 m/min), or iii) high-intensity exercise (HI: total 25 min; 5 min (5 m/min) accelerating (2 m/min) to final 1 min (15 m/min). Twenty-four hours later all rats underwent a hyperinsulinemic–hypoglycaemic clamp with measurement of CRR responses. Glucagon (240.5±27.4 ng/ml vs 134.6±11.1 ng/ml vs 219.4±31.7 ng/ml) and epinephrine (8.04±0.49 ng/ml vs 3.12±0.28 ng/ml vs 7.04±0.61 ng/ml) responses to hypoglycaemia were restored in RH animals following HI exercise (control vs LI vs HI exercise respectively). Interestingly, plasma BDNF (141.1±16.8 pg/ml vs 165.4±25.3 pg/ml vs 333.3±57.5 pg/ml) and β-endorphin (156.6±6.46 pg/ml vs 186.8±11.1 pg/ml vs 219.6±12.6 pg/ml) levels were significantly elevated in RH animals exposed to HI exercise (control vs LI vs HI exercise respectively).

These findings are consistent with the hypothesis that hypothalamic GSN habituate to RH and that introduction of a novel stimulus may re-sensitize them to further hypoglycemia trough a process of ‘dis-habitation’. Acute high-intensity exercise may represent a novel therapeutic intervention for people with impaired hypoglycaemia awareness.