[HTML][HTML] Glucagon responses to exercise-induced hypoglycaemia are improved by somatostatin receptor type 2 antagonism in a rat model of diabetes
E Leclair, RT Liggins, AJ Peckett, T Teich, DH Coy… - Diabetologia, 2016 - Springer
E Leclair, RT Liggins, AJ Peckett, T Teich, DH Coy, M Vranic, MC Riddell
Diabetologia, 2016•SpringerAims/hypothesis Regular exercise is at the cornerstone of care in type 1 diabetes. However,
relative hyperinsulinaemia and a blunted glucagon response to exercise promote
hypoglycaemia. Recently, a selective antagonist of somatostatin receptor 2, PRL-2903, was
shown to improve glucagon counterregulation to hypoglycaemia in resting streptozotocin-
induced diabetic rats. The aim of this study was to test the efficacy of PRL-2903 in enhancing
glucagon counterregulation during repeated hyperinsulinaemic exercise. Methods Diabetic …
relative hyperinsulinaemia and a blunted glucagon response to exercise promote
hypoglycaemia. Recently, a selective antagonist of somatostatin receptor 2, PRL-2903, was
shown to improve glucagon counterregulation to hypoglycaemia in resting streptozotocin-
induced diabetic rats. The aim of this study was to test the efficacy of PRL-2903 in enhancing
glucagon counterregulation during repeated hyperinsulinaemic exercise. Methods Diabetic …
Aims/hypothesis
Regular exercise is at the cornerstone of care in type 1 diabetes. However, relative hyperinsulinaemia and a blunted glucagon response to exercise promote hypoglycaemia. Recently, a selective antagonist of somatostatin receptor 2, PRL-2903, was shown to improve glucagon counterregulation to hypoglycaemia in resting streptozotocin-induced diabetic rats. The aim of this study was to test the efficacy of PRL-2903 in enhancing glucagon counterregulation during repeated hyperinsulinaemic exercise.
Methods
Diabetic rats performed daily exercise for 1 week and were then exposed to saline (154 mmol/l NaCl) or PRL-2903, 10 mg/kg, before hyperinsulinaemic exercise on two separate occasions spaced 1 day apart. In the following week, animals crossed over to the alternate treatment for a third hyperinsulinaemic exercise protocol.
Results
Liver glycogen content was lower in diabetic rats compared with control rats, despite daily insulin therapy (p < 0.05). Glucagon levels failed to increase during exercise with saline but increased three-to-six fold with PRL-2903 (all p < 0.05). Glucose concentrations tended to be higher during exercise and early recovery with PRL-2903 on both days of treatment; this difference did not achieve statistical significance (p > 0.05).
Conclusions/interpretation
PRL-2903 improves glucagon counterregulation during exercise. However, liver glycogen stores or other factors limit the prevention of exercise-induced hypoglycaemia in rats with streptozotocin-induced diabetes.
Springer