We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
133-OR: Somatostatin Receptor Type 2 Antagonism (SSTR2a) Augments Glucagon Counterregulation and Delays Hypoglycemia Onset in Type 2 Diabetic (T2D), Sprague-Dawley Rats.
- Authors
HOFFMAN, EMILY G.; DSOUZA, NINOSCHKA; AIKEN, JULIAN; LIGGINS, RICHARD; RIDDELL, MICHAEL
- Abstract
Background: SSTR2a rescues glucagon counterregulation in type 1 diabetic rats. Here, we investigated its potential for resisting hypoglycemic onset in insulin-treated rats with T2D. Methods: T2D was induced in 8-9-week-old, male, Sprague-Dawley rats (n=20) via 3-weeks of high-fat feeding and low-dose streptozotocin (35 mg/kg). After 1 week of basal insulin maintenance, N=10 healthy and N=20 T2D rats were treated with SSTR2a (3 mg/kg ZT-01, SC) or vehicle in a crossover design (1 wk apart), 60 min prior to hypoglycemic induction via insulin aspart bolus (6 U/kg). Results: SSTR2a increased plasma glucagon levels for up to 120 min after insulin challenge, with a 2.2-fold increase in glucagon AUC (32167 ± 6658 vs. 14428 ± 3673 pg*min/mL; p<0.01). Blood glucose was significantly elevated in treated, T2D rats for ∼30 min, and hypoglycemia onset was delayed by 17 ± 4 min (p<0.001). Neither effect was observed in SSTR2a-treated, healthy rats. Conclusions: SSTR2a increased glucagon secretion following insulin overdose and delayed the onset of hypoglycemia in T2D rats. SSTR2a may be a promising therapeutic tool for alleviating hypoglycemic risk in intensively-treated T2D. Disclosure: E. G. Hoffman: None. N. Dsouza: None. J. Aiken: None. R. Liggins: Employee; Self; Zucara Therapeutics Inc. M. Riddell: Advisory Panel; Self; Zealand Pharma A/S, Consultant; Self; Lilly Diabetes, Research Support; Self; Dexcom, Inc., Insulet Corporation, Speaker's Bureau; Self; Novo Nordisk Inc., Sanofi, Stock/Shareholder; Self; Zucara Therapeutics Inc. Funding: GlycoNet
- Publication
Diabetes, 2021, Vol 70, pN.PAG
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db21-133-OR