"Nature Medicine" drug treasure: human fetal intestinal endocrine cells can express insulin

When it comes to insulin, everyone is familiar with it

We all know that insulin is synthesized and secreted by pancreatic beta cells

But after all, exogenous sources are not as good as self secretion

There are not many patients who can really maintain blood sugar levels

Islet transplantation is another option for patients with loss of islet function.

Therefore, scientists believe that if other cells in the human body can also secrete insulin after induction, wouldn’t it be a perfect solution?

Recently, the team of Professor Shalev Itzkovitz of the Weizmann Institute of Science in Israel and the team of Professor Liza Konnikova of Yale University have worked together to try to find new insulin-secreting cells

They performed single-cell sequencing on human fetal intestinal cells and found that embryonic fetal intestinal K/L cells express the insulin gene

Related work was recently published in the journal Nature Medicine

In fact, studies have found that human pancreas and small intestine have a common source of tissue

The secretion mechanisms of enteroendocrine cells and pancreatic islet endocrine cells are also very similar [3]

Therefore, researchers believe that intestinal cells may have the potential to secrete insulin

We already know that the insulin gene is not expressed in mature intestinal cells

Therefore, the researchers performed single-cell RNA sequencing on 4 fetal intestinal samples and 2 neonatal intestinal samples around 20 weeks of gestation

After sequencing, the intestinal cells were divided into 11 subgroups.

However, there are many types of intestinal endocrine cells

Intestinal K/L cells include K cells and L cells
.
In single-cell sequencing, these two types of cells are usually clustered into a subgroup
.

Intestinal L cells can secrete GLP-1 (glucagon-like peptide-1), and activation of GLP-1 receptor can promote the release of insulin
.

Although intestinal L cells are closely related to insulin secretion, it has not been found that L cells can express the insulin gene before
.

To further verify this phenomenon, the researchers performed single molecule fluorescence in situ hybridization (smFISH) on the intestinal tissue of the fetus and newborn
.

The results showed that 4 cases of insulin mRNA and protein were highly expressed in 14 cases of fetal tissues (INS+ cells), but there was no expression of insulin mRNA and protein in all neonatal tissues
.

Similar to pancreatic β-cells, INS+ cells show obvious intracellular polarization (insulin mRNA expression is located at the top of the cell, and insulin protein expression is located at the base of the cell)
.

Although high expression of insulin gene has been observed in fetal intestinal tissues, the specific functions of these cells in embryonic development and insulin synthesis and secretion are still unclear
.

Itzkovitz and his colleagues speculate that because INS+ cells are not detected in all fetal intestinal samples, they may not have the necessary physiological functions
.

But there is no doubt that the discovery of these cells has greatly promoted our understanding of insulin
.

Perhaps one day, these dormant insulin production processes in diabetic patients will be awakened, allowing some diabetic patients to be truly cured
.

references:

1.
Egozi A, Llivichuzhca-Loja D, McCourt BT, Bahar Halpern K, Farack L, An X, Wang F, Chen K, Konnikova L, Itzkovitz S.
Insulin is expressed by enteroendocrine cells during human fetal development.
Nat Med.
2021 Dec;27(12):2104-2107.
doi: 10.
1038/s41591-021-01586-1.
Epub 2021 Dec 9.
PMID: 34887578.

2.
Jennings RE, Berry AA, Strutt JP, Gerrard DT, Hanley NA.
Human pancreas development.
Development.
2015 Sep 15;142(18):3126-37.
doi: 10.
1242/dev.
120063.
PMID: 26395141.

3.
Habib AM, Richards P, Cairns LS, Rogers GJ, Bannon CA, Parker HE, Morley TC, Yeo GS, Reimann F, Gribble FM.
Overlap of endocrine hormone expression in the mouse intestine revealed by transcriptional profiling and flow cytometry.
Endocrinology .
2012 Jul;153(7):3054-65.
doi: 10.
1210/en.
2011-2170.
Epub 2012 Jun 8.
PMID: 22685263; PMCID: PMC3440453.