In normal pancreatic islets, unlike isolated alpha cells, the rise in glucagon secretion at glucose concentrations above 7 mM is suppressed by paracrine action of somatostatin and insulin produced by beta cells and delta cells, respectively, and by gap junction coupling between these cells [11, 83]; but, this paracrine suppression is lost in diabetes because of alpha cell insulin and somatostatin resistance [18, 55]. Here, INS is linked to diabetes mellitus.