Peripheral resistance to insulindevelops in muscle and adipose tissue, while central resistance developsin the liver., Chronic metabolic stress inducesoxidative stress, endoplasmic reticulum stress, dedifferentiationto a precursor-like state, and apoptosis in β cells.,−, ,  β cell mass declines, although not typically to the extentobserved in type 1 diabetes (T1D), and insulin secretion decreaseswhile glucagon and somatostatin increase., Theaggregate result is an absolute or relative insulin deficiency. This evidence concerns the gene INS and type 1 diabetes mellitus.