This IISER Mohali finding may help us understand diabetes better

T V Jayan New Delhi | Updated on January 02, 2020 Published on January 02, 2020

Lolitika Mandal with Harleen Kaur in a lab at IISER, Mohali.

Other than regulating blood sugar levels in living organisms, insulin is found to play a major role in maintaining the activity of stem cells, which subsequently evolve into several different cell types.

This additional role of insulin, which was recently discovered, however, raised a pertinent question: how insulin signalling is regulated in a micro-environment in which stem cells are harboured and nurtured.

Past studies have shown that excess levels of insulin can trigger many disease conditions such as diabetes, infections, as well as, cancers.

Now a team of researchers from the Indian Institute of Science Education and Research (IISER) Mohali, may have some answers. In a first, the researchers led by Lolitika Mandal, a developmental biologist at IISER Mohali, found that the stem cell micro-environment, or niche, has an in-built mechanism to regulate the stem cells’ level of exposure to insulin.

“We have discovered that a protein present in the stem cell niche called Lar ((Leukocyte Antigen Related-like) which acts like a rheostat in regulating the level of exposure to insulin. This helps the niche to act as an interlocutor that translates physiological state of an organism to give necessary instructions to the stem or precursor cells to act,” Mandal, an associate professor of developmental genetics at IISER told BusinessLine.

The study, which is the doctoral work of Mandal’s graduate student Harleen Kaur, appeared in the journal Development recently.

The study

The IISER team, which included Shiv Kumar Sharma, another graduate student, and Sudip Mandal, an associate professor at the Institute’s Molecular Cell and Development Biology lab, studied the lymph gland, the blood-forming organ of fruit flies for the work.

This gland — similar to human bone marrow, even though both are not exactly the same — is where stem cells to be differentiated to blood cells, precursor cells and freshly-differentiated blood are cells are harboured in different compartments, before the blood cells flow out. The number of differentiated and precursor cells is controlled by the signals emanating from the niche, which is also a part of the lymph gland.

The lymph gland niche has only 40 to 50 cells and thus, it is a small, beautiful system that can be studied. Our hypothesis was that if Lar is indeed controlling insulin signalling, there would be more differentiated cells if Lar is removed from the system,” said Kaur. “Our experiments showed that in the absence of the Lar protein, the number of differentiated cells increased three to four fold,” said Kaur.

The anomaly in insulin signalling is known to be associated with deregulated blood cell formation in vertebrates. For instance, altered insulin signalling in diabetic mice is found to affect the composite micro-environment of the bone marrow, leading to compromised function of the niche which serves as reservoir for different blood cells. “Our work provides a strong genetic link between Lar and insulin signalling to tested in the vertebrates," said Mandal.

Mandal’s lab has been studying the link between diabetes and bone marrow status.

“In diabetic condition, infection is there always. People who are highly diabetic really take a long time to get over an infection. This may be because the stem cells in the (bone marrow) niche are compromised. As the next step, we plan to see whether the Lar protein plays a role in this compromised blood cell formation in diabetic people using animal models,” said the IISER Mohali researcher.

Published on January 02, 2020
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