Do we know the true mechanism of action of the DPP‐4 inhibitors?

Diabetes, Obesity and Metabolism - Tập 20 Số 1 - Trang 34-41 - 2018
Emilie S. Andersen1,2, Carolyn F. Deacon1, Jens J. Holst1
1Department of Biomedical Sciences, NNF Center of Basic Metabolic Research, The Panum Institute, Copenhagen University, Copenhagen, Denmark
2Department of Internal Medicine F, Hospital Gentofte, Copenhagen University, Copenhagen, Denmark

Tóm tắt

The prevalence of type 2 diabetes is increasing, which is alarming because of its serious complications. Anti‐diabetic treatment aims to control glucose homeostasis as tightly as possible in order to reduce these complications. Dipeptidyl peptidase‐4 (DPP‐4) inhibitors are a recent addition to the anti‐diabetic treatment modalities, and have become widely accepted because of their good efficacy, their benign side‐effect profile and their low hypoglycaemia risk. The actions of DPP‐4 inhibitors are not direct, but rather are mediated indirectly through preservation of the substrates they protect from degradation. The two incretin hormones, glucagon‐like peptide‐1 and glucose‐dependent insulinotropic polypeptide, are known substrates, but other incretin‐independent mechanisms may also be involved. It seems likely therefore that the mechanisms of action of DPP‐4 inhibitors are more complex than originally thought, and may involve several substrates and encompass local paracrine, systemic endocrine and neural pathways, which are discussed here.

Từ khóa


Tài liệu tham khảo

10.1111/dom.12610

10.1111/j.1432-1033.1993.tb17986.x

10.2337/diab.44.9.1126

10.1210/endo.136.8.7628397

10.2337/diabetes.47.5.764

10.2337/diabetes.47.11.1663

10.1210/jcem-63-2-492

10.2337/diabetes.50.7.1588

10.1172/JCI116186

10.1177/0091270006299137

10.2337/diacare.26.10.2860

10.2337/diab.44.9.1126

10.1210/jc.2006-1009

10.1152/physrev.00034.2006

10.1210/jc.2010-2178

VardarliI ArndtE DeaconCF et al. Degree of DPP‐4 inhibition after sitagliptin treatment estimated from intact and total GLP‐1 and GIP responses to oral glucose in patients with type 2 diabetes. Annual Meeting European Association for the Study Diabetes Abstract OP‐246.http://www.easdvirtualmeeting.org/resources/degree‐of‐dpp‐4‐inhibition‐after‐sitagliptin‐treatment‐estimated‐from‐intact‐and‐total‐glp‐1‐and‐gip‐responses‐to‐oral‐glucose‐in‐patients‐with‐type‐2‐diabetes(last accessed 22 May 2017).

10.1210/jc.2012-1205

10.1210/jc.2008-1135

10.1111/j.1463-1326.2012.01603.x

10.1016/j.clinthera.2005.02.008

Deacon CF, 1996, Glucagon‐like peptide 1 undergoes differential tissue‐specific metabolism in the anesthetized pig, Am J Physiol, 271, E458

10.1016/S0167-0115(99)00089-0

Hansen L, 1999, Glucagon‐like peptide‐1‐(7‐36)amide is transformed to glucagon‐like peptide‐1‐(9‐36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine, Endocrinology, 140, 5356, 10.1210/endo.140.11.7143

10.1007/s00125-011-2168-7

10.1007/s00125-005-1705-7

10.1016/j.autneu.2003.11.001

10.1210/en.2006-0153

10.1210/en.2013-1934

10.1111/j.1365-2982.2009.01317.x

10.1152/ajpregu.2000.279.4.R1449

10.2337/db15-0973

10.1210/en.2011-0286

10.1111/j.1471-4159.2011.07563.x

10.1016/j.ejphar.2016.03.030

10.1113/EP085692

10.1007/BF00572873

10.1530/EJE-13-0264

10.1152/ajpgi.00035.2013

10.1152/ajpregu.00123.2015

10.1530/JME-15-0293

10.1172/JCI7456

10.1530/JOE-11-0094

10.1053/j.gastro.2010.01.049

10.1007/s00125-012-2716-9

10.1007/s00125-014-3299-4

Rahr‐JensenK.Effect Regulation and Metabolism of DPP‐4 Substrates: Experimental Studies in the Porcine Animal Model [PhD thesis]. University of Copenhagen: Copenhagen Denmark;2011.

Willms B, 1996, Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon‐like peptide‐1 (GLP‐1)‐(7‐36) amide in type 2 (noninsulin‐dependent) diabetic patients, J Clin Endocrinol Metab, 81, 327

Nauck MA, 1997, Glucagon‐like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans, Am J Physiol, 273, E981

10.1136/gut.2004.059741

10.2337/dc15-2298

10.2337/db07-0136

10.1185/03007990802418851

10.1111/j.1365-2036.2012.05198.x

10.2337/db10-0474

10.1016/S0140-6736(08)61206-4

10.1016/j.regpep.2009.07.013

10.1111/j.1463-1326.2009.01167.x

10.1210/er.2014-1035

10.2337/db13-1455

10.2337/db16-0107

10.1677/joe.0.1720355

10.2337/diabetes.53.5.1326

10.1210/endo.141.10.7720

10.1007/s00125-008-1195-5

10.1111/dom.12395

10.2337/diabetes.50.5.1004

10.2337/db06-1033

10.1210/jc.2011-2594

10.1016/0167-0115(94)90204-6

10.1097/00006676-198906000-00002

10.1053/j.gastro.2012.04.047

10.1210/en.2015-1168

10.1530/eje.0.1340362

10.1016/j.stem.2009.02.013

10.1007/s13361-013-0822-7

10.1007/s00125-009-1384-x

10.1007/s00125-011-2181-x

10.1210/jc.2013-1029

10.1074/jbc.M212355200

10.1210/en.2004-1174

10.1016/j.ejphar.2014.09.018

10.1161/CIRCRESAHA.114.301958

10.1161/CIRCIMAGING.113.000785

10.1586/erc.12.5

10.1056/NEJMoa1307684

10.1056/NEJMoa1501352

10.1056/NEJMoa1305889

10.1007/s11033-012-2290-8

10.1056/NEJMoa1607141

10.2337/dc10-0187

10.1159/000339028

10.1038/clpt.2010.184

Singh AK, 2016, Dipeptidyl peptidase‐4 inhibitors as add‐on therapy to insulin: rationale and evidences, Expert Rev Clin Pharmacol, 1

10.1080/14728214.2016.1257608

10.1016/j.regpep.2003.10.021

10.1152/ajpendo.2000.278.6.E1010

Thông tin
Thông tin xuất bản

Diabetes, Obesity and Metabolism

Tập 20 Số 1

34-41

Thông tin tác giả