Ghrelin suppresses insulin secretion in human islets and type 2 diabetes patients have diminished islet ghrelin cell number and lower plasma ghrelin levels

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Ghrelin suppresses insulin secretion in human islets and type 2 diabetes patients have diminished islet ghrelin cell number and lower plasma ghrelin levels. / Lindqvist, A; Shcherbina, L; Prasad, R B; Miskelly, M G; Abels, M; Martínez-Lopéz, J A; Fred, R G; Nergård, B J; Hedenbro, J; Groop, L; Hjerling-Leffler, J; Wierup, N.

In: Molecular and Cellular Endocrinology, Vol. 511, 110835, 2020.

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T1 - Ghrelin suppresses insulin secretion in human islets and type 2 diabetes patients have diminished islet ghrelin cell number and lower plasma ghrelin levels

AU - Lindqvist, A

AU - Shcherbina, L

AU - Prasad, R B

AU - Miskelly, M G

AU - Abels, M

AU - Martínez-Lopéz, J A

AU - Fred, R G

AU - Nergård, B J

AU - Hedenbro, J

AU - Groop, L

AU - Hjerling-Leffler, J

AU - Wierup, N

N1 - Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

PY - 2020

Y1 - 2020

N2 - It is not known how ghrelin affects insulin secretion in human islets from patients with type 2 diabetes (T2D) or whether islet ghrelin expression or circulating ghrelin levels are altered in T2D. Here we sought out to identify the effect of ghrelin on insulin secretion in human islets and the impact of T2D on circulating ghrelin levels and on islet ghrelin cells. The effect of ghrelin on insulin secretion was assessed in human T2D and non-T2D islets. Ghrelin expression was assessed with RNA-sequencing (n = 191) and immunohistochemistry (n = 21). Plasma ghrelin was measured with ELISA in 40 T2D and 40 non-T2D subjects. Ghrelin exerted a glucose-dependent insulin-suppressing effect in islets from both T2D and non-T2D donors. Compared with non-T2D donors, T2D donors had reduced ghrelin mRNA expression and 75% less islet ghrelin cells, and ghrelin mRNA expression correlated negatively with HbA1c. T2D subjects had 25% lower fasting plasma ghrelin levels than matched controls. Thus, ghrelin has direct insulin-suppressing effects in human islets and T2D patients have lower fasting ghrelin levels, likely as a result of reduced number of islet ghrelin cells. These findings support inhibition of ghrelin signaling as a potential therapeutic avenue for stimulation of insulin secretion in T2D patients.

AB - It is not known how ghrelin affects insulin secretion in human islets from patients with type 2 diabetes (T2D) or whether islet ghrelin expression or circulating ghrelin levels are altered in T2D. Here we sought out to identify the effect of ghrelin on insulin secretion in human islets and the impact of T2D on circulating ghrelin levels and on islet ghrelin cells. The effect of ghrelin on insulin secretion was assessed in human T2D and non-T2D islets. Ghrelin expression was assessed with RNA-sequencing (n = 191) and immunohistochemistry (n = 21). Plasma ghrelin was measured with ELISA in 40 T2D and 40 non-T2D subjects. Ghrelin exerted a glucose-dependent insulin-suppressing effect in islets from both T2D and non-T2D donors. Compared with non-T2D donors, T2D donors had reduced ghrelin mRNA expression and 75% less islet ghrelin cells, and ghrelin mRNA expression correlated negatively with HbA1c. T2D subjects had 25% lower fasting plasma ghrelin levels than matched controls. Thus, ghrelin has direct insulin-suppressing effects in human islets and T2D patients have lower fasting ghrelin levels, likely as a result of reduced number of islet ghrelin cells. These findings support inhibition of ghrelin signaling as a potential therapeutic avenue for stimulation of insulin secretion in T2D patients.

U2 - 10.1016/j.mce.2020.110835

DO - 10.1016/j.mce.2020.110835

M3 - Article

C2 - 32371087

VL - 511

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

M1 - 110835

ER -