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Updated: Aug 7, 2026

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
11:10

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Published on: November 16, 2011

Ghrelin and relamorelin counteract hypoglycemia in mice engrafted with congenital hyperinsulinism stem cell-derived

Väinö Lithovius1, Hossam Montaser1, Jonna Saarimäki-Vire1

  • 1Stem Cells and Metabolism Research Program of the Faculty of Medicine, University of Helsinki, Helsinki, 00290, Finland.

Stem Cells Translational Medicine
|August 5, 2026
PubMed
Abstract

Insights

New research shows ghrelin-receptor agonists, like relamorelin, can treat hyperinsulinism by normalizing blood glucose. Combining relamorelin with octreotide offers a promising therapeutic strategy for severe cases.

Area of Science:

  • Endocrinology
  • Genetics
  • Pharmacology

Background:

  • KATP-channel-related hyperinsulinism (KATPHI) is a rare genetic disorder causing life-threatening hypoglycemia in neonates due to excessive insulin secretion.
  • Current treatments like octreotide are often ineffective for severe KATPHI, frequently leading to pancreatectomy.

Purpose of the Study:

  • To develop novel pharmaceutical therapies for KATPHI using stem cell-derived islets (SC-islets).
  • To evaluate the efficacy of candidate molecules, including ghrelin-receptor agonists, in a humanized mouse model of KATPHI.

Main Methods:

  • Differentiated stem cells with the KCNJ11-/- mutation into SC-islets to model KATPHI.
  • Tested seven candidate molecules in vitro and the most effective ones in vivo in immunocompromised mice transplanted with KCNJ11-/- SC-islets.

Main Results:

  • KCNJ11-/- SC-islets exhibited significantly higher insulin secretion in low glucose compared to controls.
  • Acyl-ghrelin and its analogue relamorelin increased blood glucose in mice.
  • A combination of relamorelin and octreotide synergistically normalized blood glucose and reduced hyperinsulinism.

Conclusions:

  • Ghrelin-receptor agonists demonstrate acute anti-hypoglycemic effects in a humanized mouse model of KATPHI.
  • The combination of relamorelin and octreotide is proposed as a potential therapeutic strategy for severe KATPHI patients, given relamorelin's safety profile in clinical trials.
Keywords:
congenital hyperinsulinismdisease modelingghrelinhypoglycemiastem cell-derived islets

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