The molecular and cellular origins of Type 1 and Type 2 diabetes are quite different and yet similar in that the body loses the ability to produce and regulate insulin secretion.  As in other common diseases that the CNM is investigating, genetic variation analyzed by genome-wide association or genome-wide sequencing indicates a minor role for genetic variation – again indicating that these diseases are not pre-determined by your genes.  CNM scientists have discovered the molecular origins of obesity-associated Type 2 diabetes emanating from pancreatic beta cell dysfunction caused by nutritional and metabolic alterations resulting in the presence of high levels of circulating lipids (fats).  The disruption of pancreatic beta cell glucose transport in individuals due to excessive lipid signaling was linked to (obesity-associated) Type 2 diabetes, with the elimination of glucose-stimulated insulin secretion and impaired insulin action together disrupting glucose sensing and cellular glycolysis.  This discovery also explains why ‘diabetes genes’ are not likely to play a significant role and why investigating ‘diabetes resistance’ genes could be a more effective approach to develop effective treatments to reverse this potentially fatal condition.  Loss of beta cell function is also the basis of Type 1 diabetes.  However, in this disease, the body’s own immune system attacks its pancreatic beta cells and destroys them, thereby leading to insulin deficiency.  CNM scientists are currently investigating the reason for this immunological attack and have acquired unexpected data implicating changes at the beta cell surface that render these cells more likely to undergo immunological attack.  CNM scientists are testing this hypothesis by altering the molecular structures existing on the beta cell surface to determine if such changes can provide protection of beta cells from immune-based destruction.