**2. Animal models of diabetes mellitus**

Type 1 diabetes mellitus is typically an immune mediated destruction of the pancreatic

β cells. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment. Animal models have been used extensively in the field of diabetes study. The current available animal models of type 1 and type 2 diabetes are shown in Table 2 (Rees and Alcolado, 2005).


**Table 2.** Animal models of type 1 and 2 diabetes mellitus

Advanced diabetic glomerulopathy is commonly characterized by diffuse glomerulosclero‐ sis and may sometimes exhibit a distinctive morphological appearance, namely, the nodular form of glomerulosclerosis, as first described by Kimmelstiel and Wilson in 1936 (Kimmel‐ stiel and Wilson, 1936; Kern et al., 1999). The stages of diabetic nephropathy are shown in

Early histologic changes: non-specific increase in basement membrane thickness, increase

Histology: mesangial nodules (Kimmelstiel-Wilson lesions), tubulointerstitial fibrosis

The current strategies to treat diabetic nephropathy include intensive glycemic control, anti‐ hypertensive treatment with a particular focus on the interruption of renin-angiotensin-al‐ dosterone system (RAS), restriction of dietary protein, and treatment of hyperlipidemia. There are several new approaches to the treatment of diabetic nephropathy based on an ev‐ er-growing mechanistic understanding of the causes of diabetic nephropathy by the specific pathogenic roles. These agents include pharmacologic inhibitors of advanced glycation end products (AGEs) formation, protein kinase C (PKC), oxidative stress, and transforming

Type 1 diabetes mellitus is typically an immune mediated destruction of the pancreatic

Histology: mesangial expansion, glomerular basement membrane thickening, arteriolar hyalinosis

Renal hyperfiltration (GFR\*↑); Normal UAER\*, blood pressure

3 Microalbuminuria (UAER 30-300mg/24 h) or incipient nephropathy GFR may elevated or reduced into normal range.

4 Established or overt nephropathy (Proteinuria, nephrotic syndrome)

Table 1 (Vora and Ibrahim, 2003).

**Stage Renal manifestation**

2 Silent stage

388 Type 1 Diabetes

5 ESRD\*\*\*

\* GFR, glomerular filtration rate \*\*UAER, urine albumin excretion rate \*\*\*ESRD, end stage renal disease

1 Renal hyperfiltration (GFR↑) Renal hypertrophy

mesangial matrix

GFR decline, Hypertension

**Table 1.** Natural course of diabetic nephropathy in type 1 diabetes

growth factor β (TGF-β) (Williams and Stanton, 2005).

**2. Animal models of diabetes mellitus**
