Table 4.

Possible mechanisms by which COS exert their related antidiabetic actions.

Model	Antidiabetic mechanism	References
Suckling piglets	Upregulation of cholesterol accumulation in suckling by the regulation of circadian clock genes	[52]
Mice	Reduction of body weight raising and adiposity; improvement of abnormal blood and liver lipid profiles	[75]
MTT colorimetric assay on pancreatic β-cells (100 mg/L); STZ-induced diabetic rats treated with COS at 500 mg/kg	Accelerate differentiation of islet cells of the pancreas; increase insulin secretion from pancreatic β-cells; reduce postprandial glucose	[82]
Enzyme-linked immunosorbent assay on pancreatic β-cells (INS-1 cells) at 100 and 500 mg/L; STZ type 2 diabetic rat models, fed on high energy diet treated by means of COS at 1000 mg/kg	Protects INS-1 cells from STZ-induced apoptosis; upregulated GLUT2 mRNA gene expression; increased proliferation of INS-1 cells; improving insulin sensitivity index (ISI)	[83]
C2C12 myotubes	Improve glucose uptake in C2C12 myotubes, even in the absence of insulin	[98]
Intestinal cell line (Caco-2) and adipocyte cell line (3T3-L1)	Suppression of intestinal glucose transporters SGLT1 and GLUT2 and α-glucosidase enzyme; enhancing adipocyte differentiation through activation of PPARc and its target genes; increase of glucose uptake; reduce hyperglycemia through suppressing the absorption of glucose and its transport	[99]
Wistar and Goto–Kakizaki (GK) rats	No antidiabetic/hypocholesterolemic effects if glycemia and cholesterol levels in GK rats are not altered	[100]
High-fat diet fed rats	Reduction of gluconeogenesis through increasing the expression of G6PC1 gene; enhancement of glucose conversion in liver through increasing the expression of GYG1 and GS2 genes	[101]
Type 2 diabetic mice	Reduction of glucose and total cholesterol levels in blood through improving their metabolism; reversal of tissue resistance to insulin	[102]
3T3-L1 cells	Adipogenesis suppression	[103]
Adipocytes (3T3-L1)	Inhibition of adipocyte proliferation stimulated via inhibiting adipogenic transcription factors' expression	[104]
3T3-L1 adipocyte	Suppression of adipocyte proliferation via activation of PPARg and C/EBPa	[105]
Obese rats	Improve dyslipidemia and prevent body weight gains by inhibiting the differentiation of adipocyte	[106]
SD rat model	Suppression of α-glucosidase enzyme activity; enhance the absorption of glucose to cells of fat and muscle	[107]
Sprague Dawley rats	Reduce cardiovascular risk factor and atherogenic index through reducing TG, LDL, and T-CHO contents in blood and enhancing their excretion in feces	[108]
Alloxan-induced mice	Decrease of glucose level in blood by increasing the insulin secretion; decrease of SGPT and SGOT levels in blood; decrease of both cholesterol and triglyceride levels	[109]
Broilers	Decrease of LDL cholesterol without any alteration in HDL cholesterol	[110]
db/db mice model	Reduction of the blood glucose level and HbA1c; suppression of sucrose, maltase, and glucoamylase enzymes	[111]
Streptozotocin-induced diabetic rats	Reduction of blood glucose concentrations; decrease of glycated hemoglobin; increase of the plasma C-peptide and insulin secretion	[112]
ob/ob mice	Ameliorated levels of adipokines by activation of PPARg gene expression; increase in adiponectin level; decrease in resistin, IL-6, and TNF-α levels	[113]
Adipose tissue of ob/ob mice	Antiobesity effect; downregulation of gene expression of PPARg and SREBP-1c	[114]
High-fat diet fed rats	Reduced VLDL/LDL ratio and TG; increased the activity of LCAT in plasma	[115]
Suckling piglets	Reduced glucose level through enhancing gluconeogenesis in the liver	[116]