title: The specific VPAC2 agonist Bay 55-9837 increases neuronal damage and hemorrhagic transformation after stroke in type 2 diabetic rats.
abstract: VPAC2 receptor is a potential target for the treatment of type 2 diabetes and may also convey neuroprotective effects. The aim of this study was to determine the potential efficacy of the VPAC2 receptor agonist Bay 55-9837 against stroke in type-2 diabetic Goto-Kakizaki (GK) rats. GK rats were treated intravenously once daily for 7 days with 0.25 or 0.025 nmol/kg Bay 55-9837 or vehicle before inducing stroke by transient middle cerebral artery occlusion. Treatments were then continued for 7 further days. The glycemic effects of Bay 55-9837 were assessed by measuring fasting blood glucose and oral glucose tolerance. The severity of stroke was measured by assessing ischemic volume. The results show that Bay 55-9837 is not effective in lowering fasting glycemia and does not facilitate glucose disposal. The highest dose of Bay 55-9837 (0.25 nmol/kg) led to increased mortality and brain hemorrhage when compared to control. The lower dose of Bay 55-9837 (0.025 nmol/kg) did not increase mortality rate but caused a threefold increase of the ischemic lesion size with signs of brain hemorrhages as compared to control. In conclusion, Bay 55-9837 did not show antidiabetic or antistroke efficacy in the type 2 diabetic GK rat. Contrarily, Bay 55-9837 treatment led to increased mortality and worsening of the severity of stroke.
authors.affiliation: Department of Clinical Science and Education, Södersjukhuset, Diabetes Research Unit, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Vladimer
authors.initials: V
authors.lastname: Darsalia
authors.forename: Shiva
authors.initials: S
authors.lastname: Mansouri
authors.forename: Petra
authors.initials: P
authors.lastname: Wolbert
authors.forename: Swapnali
authors.initials: S
authors.lastname: Barde
authors.forename: Ake
authors.initials: A
authors.lastname: Sjöholm
authors.forename: Cesare
authors.initials: C
authors.lastname: Patrone
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002452:Cell Count; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D018450:Disease Progression; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D020300:Intracranial Hemorrhages / Q000473:pathology*; D008297:Male; D020768:Middle Cerebral Artery / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000819:agonists*; D020521:Stroke / Q000473:pathology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D010446:Peptide Fragments; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; C409214:vasoactive intestinal peptide (1-7)-GRF (8-27), Lys(15)-Arg(16)-Leu(27)-; D014660:Vasoactive Intestinal Peptide