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: Jessica T Y Yue, Elena Burdett, David H Coy, Adria Giacca, Suad Efendic, Mladen Vranic
• Journal: Diabetes (Diabetes) Vol. 61 Issue 1 Pg. 197-207 (Jan 2012) ISSN: 1939-327X [Electronic] United States
• PMID: 22106159 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Hormone Antagonists
• PRL 2903
• Peptides, Cyclic
• Receptors, Somatostatin
• Sstr2 protein, rat
• Streptozocin
• Glucagon
• Glucose
• Corticosterone

Topics

• Animals
• Blood Glucose (drug effects, metabolism)
• Corticosterone (blood, metabolism)
• Cytoprotection (drug effects, physiology)
• Diabetes Mellitus, Experimental (blood, chemically induced, complications, metabolism)
• Glucagon (blood, metabolism)
• Glucose (administration & dosage, pharmacology)
• Hormone Antagonists (pharmacology)
• Hypoglycemia (blood, complications, metabolism)
• Male
• Peptides, Cyclic (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Somatostatin (antagonists & inhibitors)
• Streptozocin
• Time Factors