Incretins in the Therapy of Diabetic Kidney Disease.

Agnieszka Przezak,Weronika Bielka,Andrzej Pawlik

doi:10.3390/ijms222212312

Agnieszka Przezak, Weronika Bielka + Show 1 more

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https://doi.org/10.3390/ijms222212312

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Abstract

Diabetic kidney disease is a microvascular complication that occurs in patients with diabetes. It is strongly associated with increased risk of kidney replacement therapy and all-cause mortality. Incretins are peptide hormones derived from the gastrointestinal tract, that besides causing enhancement of insulin secretion after oral glucose intake, participate in many other metabolic processes. Antidiabetic drug classes, such as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide receptor agonists, which way of action is based on incretins facility, not only show glucose-lowering properties but also have nephroprotective functions. The aim of this article is to present the latest information about incretin-based therapy and its influence on diabetic kidney disease appearance and progression, point its potential mechanisms of kidney protection and focus on future therapeutic possibilities bound with these two antidiabetic drug classes.

Highlights

Incretins are peptide hormones derived mainly from the gastrointestinal tract which are responsible for the so-called ‘incretin effect’
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP1), hormones mostly involved in the incretin effect, are still under deep investigation which could point to possible methods of treating diseases of civilization [2]
The first medical indication of incretin-based therapy was the management of type 2 diabetes (T2D), as it results from the functional failure of β-cells triggered by insulin resistance [3]

Summary

Introduction

Incretins are peptide hormones derived mainly from the gastrointestinal tract which are responsible for the so-called ‘incretin effect’ This is defined as the enhancement of the amount of insulin secreted after oral glucose intake in comparison with the level of insulin secreted after intravenous glucose infusion resulting in the same glycaemia [1]. It was demonstrated that GLP1 infusion, but not GIP administration, may restore the proper incretin effect in T2D-affected patients in whom it is reduced or even absent [4,5]. This resulted in the development of two antidiabetic drug classes—the glucagon-like peptide receptor (GLP1R) agonists (GLP1RAs) and the dipeptidyl peptidase 4 inhibitors (DPP4is). Scientists’ attention has been drawn to the additional properties of incretin-based therapy, such as treatment of overweight and obesity, nephroprotective features, the reduction of cardiovascular risk, or beneficial effects in liver diseases and neurodegenerative disorders

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