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Amelioration of Hypoglycemia Via Somatostatin Receptor Type 2 Antagonism in Recurrently Hypoglycemic Diabetic Rats

Selective antagonism of somatostatin receptor type 2 (SSTR2) normalizes glucagon and corticosterone responses to hypoglycemic clamp in diabetic rats. The purpose of this study was to determine whether SSTR2 antagonism (SSTR2a) ameliorates hypoglycemia in response to overinsulinization in diabetic ra...

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Autores principales: Yue, Jessica T.Y., Riddell, Michael C., Burdett, Elena, Coy, David H., Efendic, Suad, Vranic, Mladen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712070/
https://www.ncbi.nlm.nih.gov/pubmed/23434929
http://dx.doi.org/10.2337/db12-1523
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author Yue, Jessica T.Y.
Riddell, Michael C.
Burdett, Elena
Coy, David H.
Efendic, Suad
Vranic, Mladen
author_facet Yue, Jessica T.Y.
Riddell, Michael C.
Burdett, Elena
Coy, David H.
Efendic, Suad
Vranic, Mladen
author_sort Yue, Jessica T.Y.
collection PubMed
description Selective antagonism of somatostatin receptor type 2 (SSTR2) normalizes glucagon and corticosterone responses to hypoglycemic clamp in diabetic rats. The purpose of this study was to determine whether SSTR2 antagonism (SSTR2a) ameliorates hypoglycemia in response to overinsulinization in diabetic rats previously exposed to recurrent hypoglycemia. Streptozotocin diabetic rats (n = 19), previously subjected to five hypoglycemia events over 3 days, received an insulin bolus (10 units/kg i.v.) plus insulin infusion (50 mU/kg/min i.v.) until hypoglycemia ensued (≤3.9 mmol/L) (experimental day 1 [Expt-D1]). The next day (Expt-D2), rats were allocated to receive either placebo treatment (n = 7) or SSTR2a infusion (3,000 nmol/kg/min i.v., n = 12) 60 min prior to the same insulin regimen. On Expt-D1, all rats developed hypoglycemia by ∼90 min, while on Expt-D2, hypoglycemia was attenuated with SSTR2a treatment (nadir = 3.7 ± 0.3 vs. 2.7 ± 0.3 mmol/L in SSTR2a and controls, P < 0.01). Glucagon response to hypoglycemia on Expt-D2 deteriorated by 20-fold in the placebo group (P < 0.001) but improved in the SSTR2a group (threefold increase in area under the curve [AUC], P < 0.001). Corticosterone response deteriorated in the placebo-treated rats on Expt-D2 but increased twofold in the SSTR2a group. Catecholamine responses were not affected by SSTR2a. Thus, SSTR2 antagonism after recurrent hypoglycemia improves the glucagon and corticosterone responses and largely ameliorates insulin-induced hypoglycemia in diabetic rats.
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spelling pubmed-37120702014-07-01 Amelioration of Hypoglycemia Via Somatostatin Receptor Type 2 Antagonism in Recurrently Hypoglycemic Diabetic Rats Yue, Jessica T.Y. Riddell, Michael C. Burdett, Elena Coy, David H. Efendic, Suad Vranic, Mladen Diabetes Original Research Selective antagonism of somatostatin receptor type 2 (SSTR2) normalizes glucagon and corticosterone responses to hypoglycemic clamp in diabetic rats. The purpose of this study was to determine whether SSTR2 antagonism (SSTR2a) ameliorates hypoglycemia in response to overinsulinization in diabetic rats previously exposed to recurrent hypoglycemia. Streptozotocin diabetic rats (n = 19), previously subjected to five hypoglycemia events over 3 days, received an insulin bolus (10 units/kg i.v.) plus insulin infusion (50 mU/kg/min i.v.) until hypoglycemia ensued (≤3.9 mmol/L) (experimental day 1 [Expt-D1]). The next day (Expt-D2), rats were allocated to receive either placebo treatment (n = 7) or SSTR2a infusion (3,000 nmol/kg/min i.v., n = 12) 60 min prior to the same insulin regimen. On Expt-D1, all rats developed hypoglycemia by ∼90 min, while on Expt-D2, hypoglycemia was attenuated with SSTR2a treatment (nadir = 3.7 ± 0.3 vs. 2.7 ± 0.3 mmol/L in SSTR2a and controls, P < 0.01). Glucagon response to hypoglycemia on Expt-D2 deteriorated by 20-fold in the placebo group (P < 0.001) but improved in the SSTR2a group (threefold increase in area under the curve [AUC], P < 0.001). Corticosterone response deteriorated in the placebo-treated rats on Expt-D2 but increased twofold in the SSTR2a group. Catecholamine responses were not affected by SSTR2a. Thus, SSTR2 antagonism after recurrent hypoglycemia improves the glucagon and corticosterone responses and largely ameliorates insulin-induced hypoglycemia in diabetic rats. American Diabetes Association 2013-07 2013-06-14 /pmc/articles/PMC3712070/ /pubmed/23434929 http://dx.doi.org/10.2337/db12-1523 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Yue, Jessica T.Y.
Riddell, Michael C.
Burdett, Elena
Coy, David H.
Efendic, Suad
Vranic, Mladen
Amelioration of Hypoglycemia Via Somatostatin Receptor Type 2 Antagonism in Recurrently Hypoglycemic Diabetic Rats
title Amelioration of Hypoglycemia Via Somatostatin Receptor Type 2 Antagonism in Recurrently Hypoglycemic Diabetic Rats
title_full Amelioration of Hypoglycemia Via Somatostatin Receptor Type 2 Antagonism in Recurrently Hypoglycemic Diabetic Rats
title_fullStr Amelioration of Hypoglycemia Via Somatostatin Receptor Type 2 Antagonism in Recurrently Hypoglycemic Diabetic Rats
title_full_unstemmed Amelioration of Hypoglycemia Via Somatostatin Receptor Type 2 Antagonism in Recurrently Hypoglycemic Diabetic Rats
title_short Amelioration of Hypoglycemia Via Somatostatin Receptor Type 2 Antagonism in Recurrently Hypoglycemic Diabetic Rats
title_sort amelioration of hypoglycemia via somatostatin receptor type 2 antagonism in recurrently hypoglycemic diabetic rats
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712070/
https://www.ncbi.nlm.nih.gov/pubmed/23434929
http://dx.doi.org/10.2337/db12-1523
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