Type 2 diabetes is associated with impaired jejunal enteroendocrine GLP-1 cell lineage in human obesity.

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.

• Authors: Céline Osinski, Léa Le Gléau, Christine Poitou, Juan de Toro-Martin, Laurent Genser, Magali Fradet, Hédi Antoine Soula, Armelle Leturque, Corinne Blugeon, Laurent Jourdren, Edwige Ludiwyne Hubert, Karine Clément, Patricia Serradas, Agnès Ribeiro
• Journal: International journal of obesity (2005) (Int J Obes (Lond)) Vol. 45 Issue 1 Pg. 170-183 (01 2021) ISSN: 1476-5497 [Electronic] England
• PMID: 33037328 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adult
• Cells, Cultured
• Diabetes Mellitus, Type 2 (complications, epidemiology, metabolism)
• Enteroendocrine Cells (cytology, metabolism)
• Female
• Humans
• Jejunum (cytology)
• Male
• Middle Aged
• Obesity (complications, epidemiology, metabolism)