INS and diabetes mellitus: It is puzzling that GLIS3 variants, do not appear to affect insulin secretion in human studies as GLIS3 has been found to be: 1) directly implemented in the transcription of INS [14], 2) been found to be involved in pancreas maturation [7], 3) been found to be involved in beta-cell apoptosis [32] and 4) the physiological consequence of GLIS3 mutations results in diabetes.