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

Autor: Jens Hjerling-Leffler, Rikard G. Fred, Mia Abels, Anders Lindqvist, Rashmi B. Prasad, Liliya Shcherbina, Leif Groop, Jan Hedenbro, J A Martínez-Lopéz, M G Miskelly, Nils Wierup, B J Nergard
Přispěvatelé: HUS Abdominal Center, Institute for Molecular Medicine Finland
Rok vydání: 2020
Předmět:
0301 basic medicine
endocrine system diseases
medicine.medical_treatment
Cell Count
Stimulation
Type 2 diabetes
Biochemistry
0302 clinical medicine
Endocrinology
STOMACH
Insulin Secretion
RNA-Seq
geography.geographical_feature_category
Stomach
digestive
oral
and skin physiology
Fasting
Islet
Ghrelin
Tissue Donors
3. Good health
Phenotype
medicine.anatomical_structure
Immunohistochemistry
hormones
hormone substitutes
and hormone antagonists
endocrine system
medicine.medical_specialty
GENES
education
030209 endocrinology & metabolism
Islets of Langerhans
03 medical and health sciences
BETA-CELLS
HUMAN PANCREATIC-ISLETS
Internal medicine
medicine
Humans
Insulin secretion
Molecular Biology
RELEASE
geography
business.industry
Insulin
nutritional and metabolic diseases
medicine.disease
Glucose
030104 developmental biology
Diabetes Mellitus
Type 2
3121 General medicine
internal medicine and other clinical medicine
1182 Biochemistry
cell and molecular biology
business
Zdroj: Molecular and Cellular Endocrinology. 511:110835
ISSN: 0303-7207
Popis: 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.
Databáze: OpenAIRE
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