PT  - JOURNAL ARTICLE
AU  - Kaiser, Julia
AU  - Krippeit-Drews, Peter
AU  - Drews, Gisela
TI  - Acyl-Ghrelin Influences Pancreatic β-Cell Function by Interference with K<sub>ATP</sub> Channels
AID  - 10.2337/db20-0231
DP  - 2021 Feb 01
TA  - Diabetes
PG  - 423--435
VI  - 70
IP  - 2
4099  - http://diabetes.diabetesjournals.org/content/70/2/423.short
4100  - http://diabetes.diabetesjournals.org/content/70/2/423.full
SO  - Diabetes2021 Feb 01; 70
AB  - The aim for this study was to elucidate how the hypothalamic hunger-inducing hormone acyl-ghrelin (AG), which is also produced in the pancreas, affects β-cell function, with particular attention to the role of ATP-sensitive K+ (KATP) channels and the exact site of action of the hormone. AG hyperpolarized the membrane potential and decreased cytoplasmic calcium concentration [Ca2+]c and glucose-stimulated insulin secretion (GSIS). These effects were abolished in β-cells from SUR1-knockout (KO) mice. AG increased KATP current but only in a configuration with intact metabolism. Unacylated ghrelin counteracted the effects of AG. The influence of AG on membrane potential and GSIS could only be averted in the combined presence of a ghrelin receptor (GHSR1a) antagonist and an inverse agonist. The inhibition of GSIS by AG could be prevented by dibutyryl cyclic–cAMP or 3-isobutyl-1-methylxanthine and the somatostatin (SST) receptor 2–5 antagonist H6056. These data indicate that AG indirectly opens KATP channels probably by interference with the cAMP/cAMP-dependent protein kinase pathway, resulting in a decrease of [Ca2+]c and GSIS. The experiments with SUR1-KO β-cells point to a direct effect of AG on β-cells and not, as earlier suggested, to an exclusive effect by AG-induced SST release from δ-cells. Nevertheless, SST receptors may be involved in the effect of AG, possibly by heteromerization of AG and SST receptors.