D'Alessio Lab

The primary focus of our research group is the regulation of insulin secretion and glucose tolerance in type 2 diabetes and specifically the influence of intestinal hormones on these processes. In addition, we have extended our work to investigate the actions of GI peptides to control food intake and body weight. Central themes that are common to all of our work is the interaction of ingested nutrients with endocrine signaling systems, and the interface between hormones and the nervous system. Our overall goal is to better understand the physiologic mechanisms underlying nutrient metabolism and apply this knowledge to the treatment of diabetes and obesity. Specific projects underway in our lab include:

1) Regulation of insulin secretion by the gut-brain peptide glucagon-like peptide 1 (GLP-1) in healthy and diabetic humans. This project focuses on the role of GI hormones in mediating the insulin response after meals and how this response is impaired in diabetes. These studies are designed to compare rates of GLP-1 secretion in response to nutrients, the sensitivity to GLP-1 action , and insulin-independent effects of GLP-1 in diabetic and control subjects.

2) Regulation of food intake by GI hormones. This project is tied to a larger study of the mechanisms by which high-fat diets induce obesity. Experiments have been designed to elucidate how chronic changes in the lipid content of the diet affect the secretion of, and responsiveness to gut peptides that regulate satiety.

3) The mechanisms by which the GLP-1 suppresses food intake. This project evaluates the hypothesis that GLP-1 inhibits food intake as part of a broader spectrum of nausea and illness actions. Studies are designed to test the hypothesis that GLP-1 is a central mediator of many of the symptoms of general illness and thus may have a role in the response to many chronic diseases.

4) The synthesis, secretion and action of a novel peptide produced in the intestinal tract. We have recently identified and isolated a peptide from the intestinal tract of mammals that has considerable homology to somatostatin, but which appears to be the product of another gene. This peptide is secreted in response to ingested nutrients, especially dietary fat, and appears to inhibit food intake. Studies are currently in progress to identify the gene producing this peptide, delineate the cells that produce it and determine a its role in normal physiology.