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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 LU ; Shcherbina, L LU ; Prasad, R B LU ; Miskelly, M G LU ; Abels, M LU ; Martínez-Lopéz, J A ; Fred, R G LU ; Nergård, B J ; Hedenbro, J LU and Groop, L LU , et al. (2020) In Molecular and Cellular Endocrinology 511.
Abstract

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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular and Cellular Endocrinology
volume
511
article number
110835
publisher
Elsevier
external identifiers
  • scopus:85084836209
  • pmid:32371087
ISSN
0303-7207
DOI
10.1016/j.mce.2020.110835
language
English
LU publication?
yes
additional info
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
id
6b68adcc-f0c8-4eef-af46-0d43acee86b7
date added to LUP
2020-05-29 12:14:24
date last changed
2024-04-03 07:00:37
@article{6b68adcc-f0c8-4eef-af46-0d43acee86b7,
  abstract     = {{<p>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.</p>}},
  author       = {{Lindqvist, A and Shcherbina, L and Prasad, R B and Miskelly, M G and Abels, M and Martínez-Lopéz, J A and Fred, R G and Nergård, B J and Hedenbro, J and Groop, L and Hjerling-Leffler, J and Wierup, N}},
  issn         = {{0303-7207}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Molecular and Cellular Endocrinology}},
  title        = {{Ghrelin suppresses insulin secretion in human islets and type 2 diabetes patients have diminished islet ghrelin cell number and lower plasma ghrelin levels}},
  url          = {{http://dx.doi.org/10.1016/j.mce.2020.110835}},
  doi          = {{10.1016/j.mce.2020.110835}},
  volume       = {{511}},
  year         = {{2020}},
}