Introduction: This study characterized a F rodent model of T2D and examined SSTR2a treatment in hypoglycemia in M and F rats with T2D.
Methods: A high fat fed streptozotocin-treated (35 mg/kg) T2D model (n=8-10/group) with impaired glucagon (GNC) counterregulation to hypoglycemia was characterized in terms of basal hyperglycemia and response to an oral glucose tolerance test (2 g/kg, OGTT). The effect of SSTR2a (3 mg/kg ZT-01) was assessed in F rats with 12 U/kg insulin-induced (aspart) hypoglycemia and compared to previously reported data for M.
Results: F had basal blood glucose 16.8 ± 5.3mmol/L and HbA1c (6.3 ± 0.6%) similar to T2D males. With OGTT, M and F glycemia were similar, but F had higher baseline c-peptide (F: 2.3 ± 0.7 vs M: 0.85 ± 0.5 ng/ml) and lower GNC (F: <5.2 vs M: 36 ± 28 ng/mL). M GNC declined during the OGTT to levels similar to F, which were unchanged throughout. ZT-01 increased GNC response in hypoglycemia which was greater in F than M (Fig).
Conclusion: We observed apparent sex-related differences to the hormonal responses to hyper- and hypoglycemia, and SSTR2a may increase glucagon responses more so in F rats with T2D.
N. DSouza: None. N. Aleali: None. D. Shakeri: None. E.G. Hoffman: None. S. Karimi-Chahartash: None. S. Javanbakhsh: None. O. Chan: None. R. Liggins: Employee; Zucara Therapeutics. Stock/Shareholder; Zucara Therapeutics. M.C. Riddell: Consultant; Eli Lilly and Company. Speaker's Bureau; Novo Nordisk. Advisory Panel; Supersapiens. Consultant; Dexcom, Inc. Speaker's Bureau; Sanofi. Advisory Panel; Zealand Pharma A/S. Speaker's Bureau; Dexcom, Inc. Stock/Shareholder; Zucara Therapeutics.
GlycoNet Strategic Initiatives (CD-85); Zucara Therapeutics Inc
