Table 2.

Features of renal injuries in some rat and mouse models of type 2 DN.

Model	Type 2	Description	Features of renal injury	Ref.
Genetically	Goto-Kakizaki (GK)	GK rat has a decreased β-cell mass and insulin resistance	☑ Glomerular hypertrophy and GBM thickening, segmental glomerulosclerosis, and tubulointerstitial fibrosis, relatively resistant to the development DN	[83–85]
	(Otsuka Long-Evans Tokushima Fatty rat) OLETF	Deficiency of CCK-A receptor in the pancreas	☑ Hypertension, glomerular hypertrophy, GBM thickening, extracellular matrix expansion, nodular lesions, diffuse glomerulosclerosis, and severe tubulointerstitial fibrosis and macroalbuminuria, glomerulosclerosis in these models appears in older rats, mild obesity, late-onset hyperglycemia	[79]
	Zucker diabetic fatty rats (ZDF)	Obese Zucker fa/fa rats×Wistar Kyoto rats, possess leptin-receptor mutation	☑ Heavy proteinuria and glomerulosclerosis tubulointerstitial and vascular damage	[80, 81]
	ZSF1	ZDF×SHHF	☑ Massive proteinuria, glomerulosclerosis, severe tubulointerstitial, vascular damage, and reduced GFR
	Ob/ob mice	Ob/ob mutation (a recessive mutation in the gene coding leptin), they are developed through β-cell atrophy and severe hyperglycemia	☑ Destruction of podocytes, proteinuria and diffuse and nodular lipohyaline	[86–90]
	Db/db mice	Mutations in the leptin receptor (similar to the Zucker rat)	☑ Glomerular hypertrophy, mesangial matrix expansion, GBM thickening do not develop advanced human DN (mesangiolysis or widespread marked or nodular mesangial sclerosis)	[92–94]
	MKR mice	Lack insulin-like growth factor 1 receptor	☑ Increased GFR, exhibit significant albuminuria nephropathy be exacerbated by uninephrectomy or high-fat diet	[102]
	Tsumura Suzuki Obese Diabetes mouse (TSOD)	Selective breeding of obese ddy strain with spontaneous DM	☑ Thickening of the glomerular basement membrane and mesangial area expansion were observed	[103, 104]
	KK mice	Is a hyperinsulinemic model that only displays mild renal pathology	☒Needs prolonged periods to develop diabetes and does not develop advanced DN	[23, 105]
	KKAy mice	KK mice×yellow obese Ay	☑ Significant elevation of albuminuria becomes progressively greater during diabetes progress	[106, 107]
	KKAy/Ta mice	Produced by transfection of the yellow obese gene (Ay) into KK/Ta mice	☑ Extracellular mesangial matrix and proliferative glomerular nephritis with expansion of glomerular	[109, 110]
	NZO (new Zealand obese mouse)	This mice has a polygenetically inherited form of diabetes	☑ Displays progressive renal pathological features as evidenced by GBM thickness and diffuse and nodular expansion of the mesangial matrix	[98]
Chemical	STZ-nicotinamide	STZ (45 to 65 mg/kg)+NA (60 to 290 mg/k) were used, NA must be injected 15 min before the administration of STZ	☑ Glomerular hypertrophy, leukocyte infiltration, and glomerulosclerosis	[34, 111, 112]
	Neonatal STZ	Injection of single dose of STZ at the dose range of 80-100 mg/kg to neonatal rats (2-5 day old) leads to induction of type 2 diabetes in adult ages	☑ Albuminuria, enhanced kidney index, and pathological changes	[114, 115]
Chemical+diet	Fat-fed STZ rat	Following 2-4 weeks of dietary intervention 60% fat diet+35 mg/kg STZ	☑ Renal injury including increasing albuminuria, kidney index, and pathological changes	[126–128]
Surgical+chemical+diet	High-fat diet in low-dose-STZ-treated, heminephrectomized	Heminephrectomy performed following injection STZ (25-40 mg/kg)+feeding these rats with high-fat chow (40-58% calories as fat)	☑ Overt proteinuria, mesangial matrix proliferation, and interstitial edema	[130–132]
Diet	Fructose-fed rats	Administrated of fructose in drinking water (10% or 20% W/V) or as 60% diet	☑ Either in drinking water or diet administration is associated with renal disorder characterized by arteriolopathy, renal hypertrophy, and glomerular hypertension	[78, 119]