Abstract
© 2024, [BioScientifica]. This is an author produced version of a paper published in Journal of Endocrinology uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.
LEAP2, a liver-derived antagonist for theghrelin receptor, GHSR1a, counteracts effects of ghrelin on appetite and energybalance. Less is known about its impact on blood glucose-regulating hormonesfrom pancreatic islets. Here we investigate whether acyl-ghrelin (AG) and LEAP2regulate islet hormone release in a cell type- and sex-specific manner. Hormonecontent from secretion experiments with isolated islets from male and femalemice was measured by radioimmunoassay and mRNA expression by qPCR. LEAP2enhanced insulin secretion in islets from males (p<0.01) but not females(p>0.2), whilst AG-stimulated somatostatin release was significantlyreversed by LEAP2 in males (p<0.001) but not females (p>0.2). Glucagonrelease was not significantly affected by AG and LEAP2. Ghsr1a, Ghrelin,Leap2, Mrap2, Mboat4 and Sstr3 islet mRNA expression did notdiffer between sexes whereas the SSTR3 antagonist MK4256 enhanced glucose-induced insulin secretion in islets from males only. In control male islets maintained without 17-betaoestradiol (E2),AG exerted an insulinostatic effect (p<0.05), with a trend towards reversalby LEAP2 (p=0.06). Both were abolished by 72h E2 pre-treatment (10 nmol/l,p>0.2). AG-stimulated somatostatin release was inhibited by LEAP2 fromcontrol (p<0.001) but not E2-treated islets (p>0.2). LEAP2and AG did not modulate insulin secretion from MIN6 beta cells and Mrap2was downregulated (P<0.05) and Ghsr1a upregulated (P<0.0001) inislets from Sst-/- mice. Our findings show that AG and LEAP2regulate insulin and somatostatin release in an opposing and sex-dependentmanner, which in males can be modulated by E2. We suggest that regulation ofSST release is a key starting point for understanding the role of GHSR1a inislet function and glucose metabolism.
LEAP2, a liver-derived antagonist for theghrelin receptor, GHSR1a, counteracts effects of ghrelin on appetite and energybalance. Less is known about its impact on blood glucose-regulating hormonesfrom pancreatic islets. Here we investigate whether acyl-ghrelin (AG) and LEAP2regulate islet hormone release in a cell type- and sex-specific manner. Hormonecontent from secretion experiments with isolated islets from male and femalemice was measured by radioimmunoassay and mRNA expression by qPCR. LEAP2enhanced insulin secretion in islets from males (p<0.01) but not females(p>0.2), whilst AG-stimulated somatostatin release was significantlyreversed by LEAP2 in males (p<0.001) but not females (p>0.2). Glucagonrelease was not significantly affected by AG and LEAP2. Ghsr1a, Ghrelin,Leap2, Mrap2, Mboat4 and Sstr3 islet mRNA expression did notdiffer between sexes whereas the SSTR3 antagonist MK4256 enhanced glucose-induced insulin secretion in islets from males only. In control male islets maintained without 17-betaoestradiol (E2),AG exerted an insulinostatic effect (p<0.05), with a trend towards reversalby LEAP2 (p=0.06). Both were abolished by 72h E2 pre-treatment (10 nmol/l,p>0.2). AG-stimulated somatostatin release was inhibited by LEAP2 fromcontrol (p<0.001) but not E2-treated islets (p>0.2). LEAP2and AG did not modulate insulin secretion from MIN6 beta cells and Mrap2was downregulated (P<0.05) and Ghsr1a upregulated (P<0.0001) inislets from Sst-/- mice. Our findings show that AG and LEAP2regulate insulin and somatostatin release in an opposing and sex-dependentmanner, which in males can be modulated by E2. We suggest that regulation ofSST release is a key starting point for understanding the role of GHSR1a inislet function and glucose metabolism.
| Original language | English |
|---|---|
| Journal | JOURNAL OF ENDOCRINOLOGY |
| DOIs | |
| Publication status | Published - 28 Oct 2024 |