Arginase: Biological and Therapeutic Implications in Diabetes Mellitus and Its Complications

Table 1

The dysregulated expression of arginase in DM complications.

DM complications	Location	Arginase expression	Species/region	Effect of arginase	Inducer or activator	Refs.
Diabetic cardiovascular disease	EC	↑ARG1	Human coronary arterioles	Reduced NO production and diminished vasodilation	Increased in DM	[15]
			Mouse aorta and BAEC	Promote vascular endothelial dysfunction	Activated by RhoA/ROC, ERK1/2, and p38 MAPK	[106]
			HUVEC	Reduced eNOS activity and induced endothelial dysfunction	Activated by p38 MAPK pathway	[107]
			Pig coronary arterioles	Induced ROS-dependent oxidative stress and impaired coronary arteriolar function	Activated by LOX-1 and JNK	[108]
			Male Wistar rats coronary arteries	Promote diabetes-induced endothelial dysfunction	Activated by p38 MAPK pathway	[109]
		↑ARG2	Male Wistar rats mesenteric arteries	Reduced expression of eNOS and impaired endothelium-dependent relaxations	Activated by p38 MAPK pathway	[109]
			Mice aorta	Induced eNOS-uncoupling and vascular dysfunction	Increased in obesity	[110]
			Rat aorta and myocardium	Reduced NO availability and impaired coronary artery microvascular function	Increased in T2DM	[111]
	RBC	↑ARG1	Rat aortas and human internal mammary arteries (IMA)	Induced endothelial dysfunction	Activated by ROS	[81]
	VSMC	↑ARG1	Human coronary arterioles and internal mammary artery	Reduced NO availability and impaired endothelial dysfunction	Increased in T2DM	[16]
Diabetic nephropathy	Macrophages	↓ARG1	Mouse renal tissues	Promote inflammation and mitochondrial dysfunction	_	[116, 117]
	Renal cortex	↑ARG2	Mouse mesangial	Promote inflammation	Increased in obese	[119]
	Kidney tissue	↑ARG2	Mice kidney	Increased blood urea nitrogen and macrophage recruitment	_	[118]
Diabetic retinopathy	Peripheral blood leukocytes	ARG1	Patients with DM	Increased susceptibility to diabetic retinopathy	ARG1 rs2781666 single nucleotide polymorphism (SNP)	[122]
	Retinal EC	↑ARG1	Mice retinal vessels	Accelerated retinal ECs senescence	Increased in DM	[123]
	Central retinal artery	↑ARG1	Rat CRA	Impaired endothelial-dependent vasodilation responses	_	[124]
	Retinal EC	↑ARG2	BREC	Increased retinal oxidative stress and inflammation	Increased in HFHS-diet	[125]
Diabetic ulcer	Epidermal keratinocytes	↓ARG1 ↑ARG2	Mice wound tissue	Induced wound healing impairment	Increased in DM	[133]
Diabetic erectile dysfunction	Cavernosal tissue	↑ARG2	Human cavernosal tissue	Decreased NO generation and CC relaxation	_	[138]
			Mice cavernosal tissue	Decreased CC relaxation	Activated by ERK pathway	[158]