ZT-01: A novel somatostatin receptor 2 antagonist for restoring the glucagon response to hypoglycaemia in type 1 diabetes.
diabetes
glucagon
hypoglycaemia
somatostatin receptor antagonist
Journal
Diabetes, obesity & metabolism
ISSN: 1463-1326
Titre abrégé: Diabetes Obes Metab
Pays: England
ID NLM: 100883645
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
02
01
2022
received:
15
10
2021
accepted:
16
01
2022
pubmed:
22
1
2022
medline:
8
4
2022
entrez:
21
1
2022
Statut:
ppublish
Résumé
To evaluate the pharmacokinetics and efficacy of a novel somatostatin receptor 2 antagonist, ZT-01, to stimulate glucagon release in rats with type 1 diabetes (T1D). The pharmacokinetics of ZT-01 and PRL-2903 were assessed following intraperitoneal or subcutaneous dosing at 10 mg/kg. We compared the efficacy of ZT-01 with PRL-2903 to prevent hypoglycaemia during an insulin bolus challenge and under hypoglycaemic clamp conditions. Within 1 hour after intraperitoneal administration, ZT-01 achieved more than 10-fold higher plasma Cmax compared with PRL-2903. Twenty-four hour exposure was 4.7× and 11.3× higher with ZT-01 by the intraperitoneal and subcutaneous routes, respectively. The median time to reach hypoglycaemia of more than 3.0 mmol/L was 60, 70, and 125 minutes following vehicle, PRL-2903, or ZT-01 administration, respectively. Furthermore, rats receiving ZT-01 had significantly higher glucose nadirs following insulin administration compared with PRL-2903- and vehicle-treated rats. During the hypoglycaemic clamp, ZT-01 increased peak glucagon responses by ~4-fold over PRL-2903. We conclude that ZT-01 may be effective in restoring glucagon responses and preventing the onset of hypoglycaemia in patients with T1D.
Substances chimiques
Blood Glucose
0
Insulin
0
Receptors, Somatostatin
0
Glucagon
9007-92-5
somatostatin receptor 2
D73QL0OMU2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
908-917Informations de copyright
© 2022 John Wiley & Sons Ltd.
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