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Cited by 75Pancreatic function and diabetesDiabetes Management and ResearchDiabetes Treatment and Management

Somatostatin Receptor Type 2 Antagonism Improves Glucagon and Corticosterone Counterregulatory Responses to Hypoglycemia in Streptozotocin-Induced Diabetic Rats

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Yue, Jessica T.Y., Burdett, Elena, Coy, David H., Giacca, Adria, Efendic, Suad, Vranic, Mladen·2012·Diabetes
DOI 10.2337/db11-0690PMC PMC3237655
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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.

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Authors
Yue, J. T. Y., Burdett, E., Coy, D. H., Giacca, A., Efendic, S., & Vranic, M.
Affiliations
  • University of Toronto (CA)
  • Tulane University (US)
  • Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
  • Department of Physiology, University of Toronto, Toronto, Ontario, Canada
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2011-12-12
Volume
61
Issue
1
Pages
197-207
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db11-0690
PMC
PMC3237655
OpenAlex
W2148438875
Cited by
75
References
44
Citations by year
2026: 4 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 12 · 2020: 5 · 2019: 6 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 1 · 2014: 6 · 2013: 7 · 2012: 4
FWCI
5.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
somatostatin receptor 2, hypoglycemia counterregulation, glucagon secretion, corticosterone, diabetes mellitus, streptozotocin-induced diabetes, insulin-induced hypoglycemia
MeSH terms
Animals, Blood Glucose, Corticosterone, Diabetes Mellitus, Experimental, Glucagon, Glucose, Hormone Antagonists, Hypoglycemia, Male, Peptides, Cyclic, Streptozocin, Time Factors, Rats, Sprague-Dawley, Receptors, Somatostatin, Cytoprotection, Rats

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