INS and type 2 diabetes mellitus: While the increase in circulating glucagon in T2D will amplify beta-cell stress through hyperglycemia, the local paracrine actions are likely to be beneficial; firstly, through a stimulatory action of glucagon on GSIS, and secondly, because GLP-1 can promote both beta-cell proliferation (at least in rodents), survival, and insulin expression and release [174,175].