Animal Models for Study of Diabetes Mellitus

Diabetes mellitus is a heterogeneous group of chronic disorders of carbohydrate, lipid and protein metabolism characterized by high blood glucose levels due to relative or absolute deficiency of insulin (Eiselein et al., 2004). Hyperglycemia, the primary clinical manifestation of diabetes, is associated with the development of diabetic complications. Several studies have suggested that hyperglycemia accelerates the development of chronic complications via several mechanisms, including increased aldose reductase related polyol pathway flux, increased formation of advanced glycation end-products (AGEs), activation of protein kinase C isoforms, increased hexosamine pathway flux, and overproduction of reactive forms of oxygen (Brownlee, 2001). AGEs are a group of complex and heterogeneous compounds, including brown and fluorescent cross-linking substances (e.g., pentosidine), non-fluorescent cross-linking products (e.g., methylglyoxal lysine dimers), or nonfluorescent, non-cross linking adducts (e.g., carboxymethyl lysine) (Dyer et al., 1991). Increasing evidence identifies AGE formation as the critical pathogenic link between hyperglycemia and long-term complications of diabetes: nephropathy, neuropathy, and retinopathy (Wada & Yagihashi, 2005). Therefore, another mode of diabetes treatment independent of blood glucose levels, inhibition of AGE formation, could be useful in the prevention or reduction of certain diabetic complications (Dong et al., 2010) in both main forms of the illness, Type 1 diabetes mellitus (T1D, insulin-dependent diabetes mellitus, IDDM) and Type 2 diabetes mellitus (T2D, noninsulin-dependent diabetes mellitus, NIDDM), and also in secondary forms related to gestation or other disorders.