Type 2 diabetes is associated with impaired jejunal enteroendocrine GLP-1 cell lineage in human obesity
Enteroendocrine cell (EEC) is associated with therapeutic benefit during type 2 diabetes. There is little information about the altered function of EEC in obesity and type 2 diabetes. Osinski and colleagues conducted research titled “Type 2 diabetes is associated with impaired jejunal enteroendocrine GLP-1 cell lineage in human obesity” published in the International Journal of Obesity. A summary of the findings is provided below:
Objective:
To investigate the impact of type 2 diabetes and obesity on human EEC.
Method:
By using the cell sorting method, EEC isolation from the jejunum of obese individuals with (ObD) or without (Ob) type 2 diabetes was collected. In the first group (14Ob, 13 Obd), EEC transcriptional profile was created by RNA sequencing. In the jejunum of the second independent group (37 Ob, 21 Obd, and 22 non-obese (NOb) participants), EEC density and lineage were studied.
Findings:
The study showed discriminated EEC transcriptomic signature in obese individually depending on their diabetic status. Analysis of EEC lineage revealed a decrease in the differential programs in individuals with obesity and type 2 diabetes. The above-mentioned finding is confirmed by a specific reduction of GLP-1 lineage and hormone synthesis in the second study group. There is a reduction in GLP-1 positive cell density in individuals with type 2 diabetes along with obesity. On the other hand, the density of cholecystokinin (CCK-), peptide YY (PPY-), and glucagon-like peptide-1 (GIP) producing cell remain unaffected. The study suggests a rise in GLP-1 secretion instantaneously after bariatrics surgery. The findings in the study led to a new strategy to avoid a decrease in postprandial GLP-1 production for improved diabetes outcomes by intervening EEC lineage.
Limitations:
The authors acknowledge that the results cannot be excluded to other segments of the small intestine as findings are limited to the jejunum. The impact of antidiabetic treatment on gene expression in Obd patients was not feasible. Though there were gender differences in individuals undergoing bariatric surgery, the study didn’t abled to exclude sex-biased gene expression. The causal link between diabetes and the transcriptomic profile of EEC is unclear.
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