Type 2 diabetes is associated with impaired jejunal enteroendocrine GLP-1 cell lineage in human obesity.
Int J Obes (Lond)
; 45(1): 170-183, 2021 01.
Article
in En
| MEDLINE
| ID: mdl-33037328
ABSTRACT
OBJECTIVES:
Altered enteroendocrine cell (EEC) function in obesity and type 2 diabetes is not fully understood. Understanding the transcriptional program that controls EEC differentiation is important because some EEC types harbor significant therapeutic potential for type 2 diabetes.METHODS:
EEC isolation from jejunum of obese individuals with (ObD) or without (Ob) type 2 diabetes was obtained with a new method of cell sorting. EEC transcriptional profiles were established by RNA-sequencing in a first group of 14 Ob and 13 ObD individuals. EEC lineage and densities were studied in the jejunum of a second independent group of 37 Ob, 21 ObD and 22 non obese (NOb) individuals.RESULTS:
The RNA seq analysis revealed a distinctive transcriptomic signature and a decreased differentiation program in isolated EEC from ObD compared to Ob individuals. In the second independent group of ObD, Ob and NOb individuals a decreased GLP-1 cell lineage and GLP-1 maturation from proglucagon, were observed in ObD compared to Ob individuals. Furthermore, jejunal density of GLP-1-positive cells was significantly reduced in ObD compared to Ob individuals.CONCLUSIONS:
These results highlight that the transcriptomic signature of EEC discriminate obese subjects according to their diabetic status. Furthermore, type 2 diabetes is associated with reduced GLP-1 cell differentiation and proglucagon maturation leading to low GLP-1-cell density in human obesity. These mechanisms could account for the decrease plasma GLP-1 observed in metabolic diseases.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Enteroendocrine Cells
/
Diabetes Mellitus, Type 2
/
Jejunum
/
Obesity
Type of study:
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Int J Obes (Lond)
Journal subject:
METABOLISMO
Year:
2021
Type:
Article
Affiliation country:
France