title: Glucagon responses to exercise-induced hypoglycaemia are improved by somatostatin receptor type 2 antagonism in a rat model of diabetes.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: School of Kinesiology and Health Science, York University, Toronto, ON, M3J 1P3, Canada.
authors.forename: Erwan
authors.initials: E
authors.lastname: Leclair
authors.affiliation: The Center for Drug Research and Development, Vancouver, BC, Canada.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Liggins
authors.affiliation: School of Kinesiology and Health Science, York University, Toronto, ON, M3J 1P3, Canada.
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Peckett
authors.affiliation: School of Kinesiology and Health Science, York University, Toronto, ON, M3J 1P3, Canada.
authors.forename: Trevor
authors.initials: T
authors.lastname: Teich
authors.affiliation: Department of Medicine, Peptide Research Labs, Tulane University Medical Center, New Orleans, LA, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Coy
authors.affiliation: Departments of Physiology and Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Mladen
authors.initials: M
authors.lastname: Vranic
authors.affiliation: School of Kinesiology and Health Science, York University, Toronto, ON, M3J 1P3, Canada. mriddell@yorku.ca.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Riddell
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004195:Disease Models, Animal; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007003:Hypoglycemia / Q000188:drug therapy* / Q000209:etiology*; D007328:Insulin / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010456:Peptides, Cyclic / Q000627:therapeutic use; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*
chemical_list: D001786:Blood Glucose; D007328:Insulin; C121568:PRL 2903; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; D005934:Glucagon; C093733:somatostatin receptor 2; D005947:Glucose
keywords: Exercise; Glucagon; Hypoglycaemia; Somatostatin receptor antagonist; Type 1 diabetes