PathWhiz

Pathway Description

Nateglinide Action Pathway (New)

Homo sapiens

Drug Action Pathway

Nateglinide is an antihyperglycemic agent, a meglitinide one. It is used in the treatment of non insulin dependent diabetes mellitus (NIDDM). This drug had the function to increase the insulin release by the pancreas to the blood. It does this by inhibiting the ATP-sensitive potassium channels in a glucose-dependent manner. This drug does not act on the insulin level without the presence of glucose, which differentiates it from sulfonylurea drugs. The mechanism of action starts with the need for functioning beta cells in the pancreas and glucose in the blood. Since the release of insulin is controlled by the beta cells membrane potential, the binding of the drug to the ATP-binding cassette subfamily C member 8 causes its closing. This results in the depolarization of the cell and the opening of the L-type calcium channels. In consequence, the increased concentration of calcium results in the stimulation of the calcium-dependent exocytosis of insulin granules. An overdose of this drug may result in the development of hypoglycemic symptoms. Nateglinide is administered as an oral tablet.

References

Nateglinide Pathway (New) References

Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.

Pubmed: 29126136

Hu S, Wang S, Fanelli B, Bell PA, Dunning BE, Geisse S, Schmitz R, Boettcher BR: Pancreatic beta-cell K(ATP) channel activity and membrane-binding studies with nateglinide: A comparison with sulfonylureas and repaglinide. J Pharmacol Exp Ther. 2000 May;293(2):444-52.

Pubmed: 10773014

Sunaga Y, Gonoi T, Shibasaki T, Ichikawa K, Kusama H, Yano H, Seino S: The effects of mitiglinide (KAD-1229), a new anti-diabetic drug, on ATP-sensitive K+ channels and insulin secretion: comparison with the sulfonylureas and nateglinide. Eur J Pharmacol. 2001 Nov 9;431(1):119-25. doi: 10.1016/s0014-2999(01)01412-1.

Pubmed: 11716850

Hansen AM, Christensen IT, Hansen JB, Carr RD, Ashcroft FM, Wahl P: Differential interactions of nateglinide and repaglinide on the human beta-cell sulphonylurea receptor 1. Diabetes. 2002 Sep;51(9):2789-95. doi: 10.2337/diabetes.51.9.2789.

Pubmed: 12196472

Chachin M, Yamada M, Fujita A, Matsuoka T, Matsushita K, Kurachi Y: Nateglinide, a D-phenylalanine derivative lacking either a sulfonylurea or benzamido moiety, specifically inhibits pancreatic beta-cell-type K(ATP) channels. J Pharmacol Exp Ther. 2003 Mar;304(3):1025-32. doi: 10.1124/jpet.102.044917.

Pubmed: 12604678

Norman P, Rabasseda X: Nateglinide: A structurally novel, short-acting, hypoglycemic agent. Drugs Today (Barc). 2001 Jun;37(6):411-426. doi: 10.1358/dot.2001.37.6.627960.

Pubmed: 12764427

Dornhorst A: Insulinotropic meglitinide analogues. Lancet. 2001 Nov 17;358(9294):1709-16. doi: 10.1016/S0140-6736(01)06715-0.

Pubmed: 11728565

Highlighted elements will appear in red.

Highlight Compounds

	Adenosine triphosphate
	Calcium
	D-Glucose
	Nateglinide
	Potassium

Highlight Proteins

	ATP-binding cassette sub-family C member 8
	Insulin
	Solute carrier family 2, facilitated glucose transporter member 4
	Voltage-dependent calcium channel subunit alpha-2/delta-2

Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.

Visualize Compound Data

		Adenosine triphosphate
		Calcium
		D-Glucose
		Nateglinide
		Potassium

Visualize Protein Data

		ATP-binding cassette sub-family C member 8
		Insulin
		Solute carrier family 2, facilitated glucose transporter member 4
		Voltage-dependent calcium channel subunit alpha-2/delta-2

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