Type 2 diabetes is a complex multifactorial disease in which a pathological combination of metabolic and genetic factors severely affects the normally exquisite control of blood glucose levels performed by our metabolic organs. There are two highly specialized endocrine cells in the pancreas that secrete hormones that can abruptly change blood glucose levels: the insulin-secreting beta cells and the glucagon-secreting alpha cells. These perplexing cells have diametrically opposed functions: insulin is secreted at high blood glucose levels to promote efficient glucose absorption into our organs while glucagon is secreted at low blood glucose levels to trigger release of glucose from our organs. The delicate balance in secretion of insulin and glucagon forms the basis through which our bodies maintain healthy blood glucose levels at all times.

Various cellular mechanisms control the function of alpha and beta cells, including the fine-tuning of hormone production and secretion in response to subtle changes in the environment, which are sensed through the metabolism of the nutrients circulating in our blood. Unfortunately, for the most part, these basic mechanisms are still poorly understood because of the difficulty in analyzing human alpha and beta cells due to their anatomical configuration and low abundance in our body. In particular, there is very little information regarding how do human alpha cells metabolize sugars, lipids and amino acids.  Recently, in our laboratory we have developed novel methods that allow us to efficiently isolate numerous human alpha and beta cells and perform many different types of experiments and analyses. Using these new techniques, we will perform a comprehensive characterization of the metabolism of human beta and alpha cells to understand how they react to the changing metabolic status that is a hallmark of type 2 diabetes.

In addition, we believe that the different ways alpha and beta cells metabolize nutrients to generate new metabolic molecules is intimately linked to how they control the activation or inhibition of specific genes that help to define the key differences between these two cell types. Like for example the decision to whether produce glucagon or insulin as a hormone. Thus, to better understand this process, we will also study how does the metabolism of alpha and beta cells impact the activity of genes that maintain their key diametrically-opposed cellular and physiological differences.

The results from our experiments will generate important and basic information about the key role of metabolism in human pancreatic alpha and beta cell biology, which will be highly relevant to understand how Type 2 Diabetes develops given the strong link between the disease and metabolic dysregulation.