Ghrelin and relamorelin alleviate hypoglycaemia in humanised mice with congenital hyperinsulinism Article Swipe
Väinö Lithovius
,
Hossam Montaser
,
Jonna Saarimäki‐Vire
,
Hazem Ibrahim
,
Tom Barsby
,
Diego Balboa
,
Timo Otonkoski
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.10.02.680116
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.10.02.680116
K ATP -channel related hyperinsulinism (K ATP HI) is a genetic disorder of the pancreatic beta cells, manifesting as life-threatening hypoglycaemia in neonates due to dysregulated insulin secretion. Management of the severe diffuse form of K ATP HI currently lacks treatment options, as the first-line therapy octreotide is often insufficiently effective, necessitating radical pancreatectomy in many patients. In this study, we applied stem cell derived islets carrying K ATP HI-causing mutation KCNJ11 -/- to develop new pharmaceutical therapies for K ATP HI. We tested seven candidate molecules in vitro, identifying three that reduced insulin secretion in KCNJ11 -/- stem cell derived islets. Of these, we tested acyl-ghrelin and its long-acting analogue relamorelin in mice that became hypoglycaemic due to carrying human KCNJ11 -/- stem cell derived grafts. Acyl-ghrelin and relamorelin alone increased fasting glycaemia. Combining relamorelin with octreotide increased blood glucose more than the sum of each drug alone, reversing hypoglycaemia to normoglycaemia. In conclusion, we show that ghrelin receptor agonists have acute anti-hypoglycaemic effects in a humanised mouse model of K ATP HI, especially when combined with octreotide. Relamorelin has been tested in >650 diabetic adults with little side effects, leading us to propose relamorelin- octreotide combination as a novel therapeutic candidate for severe K ATP HI patients.
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- Type
- article
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- https://doi.org/10.1101/2025.10.02.680116
- https://www.biorxiv.org/content/biorxiv/early/2025/10/02/2025.10.02.680116.full.pdf
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Ghrelin and relamorelin alleviate hypoglycaemia in humanised mice with congenital hyperinsulinismWork title
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articleOpenAlex work type
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enPrimary language
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2025Year of publication
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2025-10-02Full publication date if available
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Väinö Lithovius, Hossam Montaser, Jonna Saarimäki‐Vire, Hazem Ibrahim, Tom Barsby, Diego Balboa, Timo OtonkoskiList of authors in order
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https://doi.org/10.1101/2025.10.02.680116Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2025/10/02/2025.10.02.680116.full.pdfDirect link to full text PDF
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2025/10/02/2025.10.02.680116.full.pdfDirect OA link when available
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| abstract_inverted_index.acyl-ghrelin | 106 |
| abstract_inverted_index.dysregulated | 25 |
| abstract_inverted_index.relamorelin- | 195 |
| abstract_inverted_index.hypoglycaemia | 20, 150 |
| abstract_inverted_index.hypoglycaemic | 116 |
| abstract_inverted_index.necessitating | 51 |
| abstract_inverted_index.insufficiently | 49 |
| abstract_inverted_index.pancreatectomy | 53 |
| abstract_inverted_index.pharmaceutical | 76 |
| abstract_inverted_index.hyperinsulinism | 4 |
| abstract_inverted_index.normoglycaemia. | 152 |
| abstract_inverted_index.life-threatening | 19 |
| abstract_inverted_index.anti-hypoglycaemic | 163 |
| cited_by_percentile_year | |
| corresponding_author_ids | https://openalex.org/A5066204513 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 7 |
| corresponding_institution_ids | https://openalex.org/I133731052 |
| citation_normalized_percentile.value | 0.59750378 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |