Stimulation of insulin release by repaglinide and glibenclamide involves both common and distinct processes.
Level 5 - mechanism / opinion, no new human data
Bench and animal comparative pharmacology study without human participants
PubMed 9519738 · doi:10.2337/diabetes.47.3.345
What was done
The action of the novel insulin secretagogue repaglinide was compared with the sulfonylurea glibenclamide across multiple preclinical assays: in vitro receptor binding to betaTC-3 cells, single-cell exocytosis in voltage-clamped mouse beta-cells, insulin release from perifused mouse islets, and in vivo hypoglycemic potency (intravenous and oral) in non-diabetic and low-dose streptozotocin diabetic rats.
What was found
Two binding sites were identified: a high-affinity repaglinide site (KD = 3.6 nmol/l; glibenclamide KD = 14.4 nmol/l) and a high-affinity glibenclamide site (KD = 25 nmol/l; repaglinide KD = 550 nmol/l). In voltage-clamped beta-cells, repaglinide up to 5 micromol/l did not enhance exocytosis, unlike glibenclamide. Repaglinide showed higher potency than glibenclamide in stimulating insulin release from perifused islets (EC50 29 vs. 80 nmol/l). In vivo ED50 values for hypoglycemic action were 10.4 vs. 70.3 microg/kg (intravenous) and 15.6 vs. 203.2 microg/kg (oral) for repaglinide and glibenclamide, respectively. Repaglinide (1 mg/kg orally) significantly stimulated insulin release in diabetic rats (P < 0.001).
Why it matters
This study demonstrates that repaglinide acts as a potent insulinotropic agent via mechanisms partially distinct from classical sulfonylureas, notably operating through a distinct high-affinity site without directly augmenting exocytosis.
Limits
The study is entirely preclinical, relying on rodent cell lines, isolated mouse islets, and rat models, which may not fully reflect human pharmacokinetics or safety. Exact animal and cell sample sizes were not reported in the abstract.
Cited by
- supports Repaglinide functions by stimulating the release of insulin from pancreatic beta cells.