Diminished insulin secretion and growth hormone counter regulationin the etiology of type 2 diabetes mellitus and cancer: Studies in two cohorts of human subjects with low insulin secretion and opposing metabolic phenotype

This thesis explores the cellular mechanisms by which diminished insulin secretion (DIS) affects disease incidence, depending on the actions that a pituitary hormone -called growth hormone (GH)- has on the regulation of carbohydrate (CHO) metabolism.
The objectives are addressed by comparing two groups of subjects with severe short stature and DIS. Individuals belonging to one cohort (Laron Syndrome -LS-) display diminished incidence of type 2 diabetes mellitus (T2D) and cancer. They have (GH) insensitivity due to a mutation in the GH receptor gene. Subjects in the other cohort (Guevara-Rosenbloom Syndrome -GRS-) also have DIS; however, it is accompanied by a dramatic increase of T2D incidence. GRS is produced by a mutation in a gene called CDKN1c. In summary, LS and GRS individuals both have DIS but an opposing T2D incidence due to the different regulation that GH has on CHO metabolism in each group.