Fig. 1. Intra-islet insulin & glucagon secretion. Normal (in nondiabetes) and advanced type 2 diabetes (T2D) of the relationship between the inhibitory effects of pancreatic β-cell insulin secretion on pancreatic α-cell glucagon secretion. Normally, an increase in plasma glucose level causes an increase in β-cell insulin secretion that prevents an increase in α-cell glucagon secretion in response to meal. In advanced T2D, however, β-cell failure which is lack of intra-islet signaling result in not only fail to suppress but also an increase in pancreatic α-cell glucagon secretion (A). A decrease in plasma glucose level causes a decrease in β-cell insulin secretion that signals an increase in α-cell glucagon secretion during hypoglycemia. On the other hand, in the advanced T2D, a decrease in plasma glucose cannot cause a decrease in β-cell insulin secretion, and the absence of that signal results in no increase in pancreatic α-cell glucagon secretion during hypoglycemia (B).