New stem cell model mimics alpha cell behavior in diabetic conditions

Mor than 800 million people worldwide are living with diabetes, according to World Health Organization (WHO) estimates, with numbers steadily increasing. Diabetic patients experience abnormally high levels of blood sugar, which can, over the long-term, damage organs and decrease the quality of life and life expectancy of patients.

Blood sugar levels are controlled by cells in the pancreas called beta-cells which secrete insulin to lower blood glucose levels. Another cell type in the pancreas called alpha-cells are the natural counterpart of beta-cells as they act to increase blood sugar levels by secreting the hormone glucagon. A precisely tuned secretion of insulin versus glucagon is required to keep blood sugar at the right level.

While much research has focused on understanding beta-cell dysfunction in diabetic patients, it has become clear that alpha-cells are also affected in diabetes. Lab-based models of human alpha cells are crucial for understanding alpha-cell (dys)function and blood sugar regulation. Recently, Quinn Peterson and colleagues from Mayo Clinic, USA, discovered a method for making human alpha cells from cultures of immature stem cells. This work was recently published in Stem Cell Reports.

These stem cell-derived alpha cells very closely resembled pancreas-derived alpha cells and secreted comparable levels of glucagon. Importantly, like alpha cells in diabetic patients, the stem cell-derived alpha cells responded to culture conditions mimicking a diabetic environment with elevated glucagon secretion and dysregulation of alpha cell gene expression and physiology. Encouragingly, abnormal glucagon secretion of these cells was reversed by a drug called Sunitinib (a clinically approved anti-cancer drug). The human alpha cells described in this research will be a useful model to understand diabetic alpha cell dysfunction and to screen for new therapeutics.