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Prolonged Somatostatin Receptor 2 Antagonism Enhances Glucagon Response to Hypoglycemia in Male Diabetic Rats

Ninoschka C D'Souza1, Nadia Aleali1, Dorsa Shakeri1

  • 1School of Kinesiology & Health Science, York University, Toronto, ON M3J 1P3, Canada.

Endocrinology
|January 8, 2026
PubMed

Insights

Somatostatin receptor antagonist (SSTR2a) treatment improved glucagon counterregulation during hypoglycemia in a type 2 diabetes model. This approach shows potential for managing blood sugar in diabetes.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Pharmacology

Background:

  • Glucagon dysregulation is common in diabetes, impacting blood glucose control.
  • Somatostatin receptor antagonists (SSTR2a) show promise in enhancing glucagon counterregulation in type 1 diabetes models.
  • The effect of SSTR2a on glucagon in type 2 diabetes (T2D) requires further investigation.

Purpose of the Study:

  • To evaluate the impact of daily SSTR2a administration on glucagon and glycemia in a rodent model of insulin-treated T2D.
  • To assess SSTR2a's effects on glucagon counterregulation during hypoglycemia and overall glycemic control.

Main Methods:

  • Rodent model of insulin-requiring T2D.
  • Daily administration of SSTR2a at different doses (3.0 mg/kg and 0.3 mg/kg/d) over 8 and 11 days, respectively.
  • Evaluation of glucagon levels, glycemic response to insulin, and HbA1c.

Main Results:

  • Low-dose SSTR2a (0.3 mg/kg/d) increased glucagon counterregulation to insulin-induced hypoglycemia and delayed hypoglycemic onset.
  • SSTR2a treatment did not negatively affect food intake, body mass, or C-peptide levels.
  • A significant reduction in HbA1c was observed in the SSTR2a-treated group compared to controls (4.3% vs 5.3%).

Conclusions:

  • Daily SSTR2a administration enhances glucagon counterregulatory responses to hypoglycemia in a T2D rat model.
  • SSTR2a treatment improved glycemic control, indicated by lower HbA1c, without impairing insulin sensitivity.
  • SSTR2a represents a potential therapeutic strategy for improving glucose homeostasis in T2D.
Keywords:
SSTR2acounterregulationglucagonhypoglycemiasomatostatintype 2 diabetes

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