Table 2.

Effects of ginseng on different molecular targets related to diabetes in cell line studies

Material	Cell line	Molecular mechanism	Reference
American ginseng
Root	HIT-T15	Insulin secretion ↑ (EC50=178.9 mg/mL)	[33]
	INS-1	Insulin production/secretion ↑, UCP-2↓, ATP↑, Bcl2↑, caspase-9↓	[34]
Asian ginseng
Root	MIN6N8	Cytokine-induced β-cell apoptosis ↓, NO & ROS production ↓, p53/p21↓, caspase ↓, PARP ↓	[35]
Root (KRG)	Rat pancreatic islets	Insulin secretion ↑ (glucose-independent manner)	[36]
Notoginseng
Saponins	3T3-L1	Glucose uptake & glycogen synthesis ↑	[37]
Fermented ginseng (β-galactosidase treated)
Root	RINm5F	iNOS, COX-2 & TNF-α ↓ NF-κB & MAPK (ERK and JNK) ↓	[38]
PPD type saponin
Rb1	3T3-L1	Glucose uptake ↑, GLUT1 & GLUT4 translocation ↑	[39]
	MIN6N8	Insulin secretion ↑	[40]
Rb2	H4IIE	Hepatic gluconeogenesis ↓, LKB1, AMPK & SHP ↑, G6Pase & PEPCK ↓	[41]
Rc	C2C12	Glucose uptake↑, ROS ↑, AMPK ↑, p38↑	[42]
Rg3	L6 myotubes	Glucose uptake ↑, IRS-1 & GLUT4 expression ↑	[43]
	C2C12	Glucose uptake ↑, CaMKK & AMPK ↑	[44]
	MIN6N8	Palmitate-induced apoptosis ↓, MAPK ↓	[45]
	3T3-L1	Glucose uptake ↑, GLUT4 ↑, IRS & PI3K ↑	[46]
Compound K	Caco-2	SGLT1↑, GLUT1, GLUT2 & GLUT3 ↑	[47]
PPD	RMC	Rb1, Rb2 & Rg3 - fibronectin expression ↓ Re & Rd - fibronectin expression × Rb1 - MAPK and Akt phosphorylation ↑	[48]
PPT type saponin
Re	3T3-L1	Glucose uptake ↑, GLUT4 ↑, IRS & PI3K ↑	[46]
	HepG2	Hepatic gluconeogenesis ↓ , AMPK ↑ , SREBP-1c ↓	[49]
Rg1	MIN6N8	Insulin secretion ↑	[40]
	Caco-2	SGLT1 ↓ , GLUT1, GLUT2 & GLUT3 ×	[47]
	HepG2	Hepatic gluconeogenesis ↓, AMPK ↑	[50]
PPT	3T3-L1	PPAR-γ ↑, aP2 ↑, LPL ↑, PEPCK ↓, GLUT4 ↑	[51]

AMPK, AMP-activated protein kinase; aP2, fatty acid binding protein; Bcl2, B-cell lymphoma 2; CaMKK, calcium/calmodulin-dependent protein kinase kinase; COX-2, cyclooxygenase-2; ERK1/2, extracellular signal-regulated kinase; GLUT, glucose transporter; iNOS, inducible nitric oxide synthase; IRS, insulin-receptor substrate; JNK, c-jun NH2-terminal kinase; KRG, Korean red ginseng; LKB1, liver kinase B1; LPL, lipoprotein lipase; MAPK, mitogen activated protein kinase; NF-κB, nuclear factor-κB; NO, nitrite oxide; PARP, poly (ADP-ribose) polymerase; PEPCK, phosphoenolpyruvate carboxykinase; PI3K, phosphatidylinositide 3 kinase; PPAR-γ, peroxisome proliferator-activated receptor γ; PPD, protopanaxadiol; PPT, protopanaxatriol; RMC, rat mesangial cell; ROS, reactive oxygen species; SGLT1, sodium-glucose cotransporter 1; SHP, small heterodimer partner; SREBP, sterol regulatory element-binding protein; TNF-α, tumor nuclear factor-α; UCP, uncoupling protein.