Erwan Leclair1, Richard T Liggins2, Ashley J Peckett1, Trevor Teich1, David H Coy3, Mladen Vranic4, Michael C Riddell5. 1. School of Kinesiology and Health Science, York University, Toronto, ON, M3J 1P3, Canada. 2. The Center for Drug Research and Development, Vancouver, BC, Canada. 3. Department of Medicine, Peptide Research Labs, Tulane University Medical Center, New Orleans, LA, USA. 4. Departments of Physiology and Medicine, University of Toronto, Toronto, ON, Canada. 5. School of Kinesiology and Health Science, York University, Toronto, ON, M3J 1P3, Canada. mriddell@yorku.ca.
Abstract
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.
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 diabeticrats. The aim of this study was to test the efficacy of PRL-2903 in enhancing glucagon counterregulation during repeated hyperinsulinaemic exercise. METHODS:Diabeticrats 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 diabeticrats 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.
Entities:
Keywords:
Exercise; Glucagon; Hypoglycaemia; Somatostatin receptor antagonist; Type 1 diabetes
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