title: Somatostatin receptor type 2 antagonism improves glucagon and corticosterone counterregulatory responses to hypoglycemia in streptozotocin-induced diabetic rats.
abstract: Diminished responsiveness to hypoglycemia contributes to defective counterregulation in diabetes. Pancreatic and/or circulating somatostatin are elevated in diabetes, which may inhibit counterregulatory hormone release during hypoglycemia. Thus, a selective somatostatin receptor type 2 antagonist (SSTR2a) should improve hormone counterregulation to hypoglycemia. Nondiabetic (N) and streptozotocin-induced diabetic (D) rats underwent 4-h infusion of saline or SSTR2a with insulin-induced hypoglycemia clamped at 2.5 ± 0.5 mmol/L. To evaluate the effect of the SSTR2a in the absence of hypoglycemia, rats underwent a 4-h infusion of saline (Ctrl:N, Ctrl:D) or SSTR2a (Ctrl:D+SSTR2a) only. The attenuated glucagon response to hypoglycemia in D (P < 0.0002) was fully restored by SSTR2a (P < 0.0001). Furthermore, the attenuated corticosterone response in D (P < 0.002) was also enhanced by SSTR2a (P < 0.05). In the absence of hypoglycemia, SSTR2a did not alter basal blood glucose levels. D exhibited 62% more pancreatic somatostatin than N after hypoglycemia. In N rats, SSTR2a did not augment the glucagon or corticosterone response to hypoglycemia. Thus, somatostatin may contribute to impaired glucagon responsiveness to hypoglycemia in diabetes. We demonstrate that SSTR2 antagonism enhances hypoglycemia-stimulated glucagon and corticosterone release in D but not in N rats. SSTR2 antagonism does not affect basal glycemia in D rats.
authors: Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors: Jessica T Y
authors: JT
authors: Yue
authors: Elena
authors: E
authors: Burdett
authors: David H
authors: DH
authors: Coy
authors: Adria
authors: A
authors: Giacca
authors: Suad
authors: S
authors: Efendic
authors: Mladen
authors: M
authors: Vranic
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology*; D007003:Hypoglycemia / Q000097:blood / Q000150:complications / Q000378:metabolism*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013311:Streptozocin; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D006727:Hormone Antagonists; C121568:PRL 2903; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C115977:Sstr2 protein, rat; D013311:Streptozocin; D005934:Glucagon; D005947:Glucose; D003345:Corticosterone