Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Exploring the Pathophysiology of ATP-Dependent Potassium Channels in Insulin Resistance

Version 1 : Received: 7 March 2024 / Approved: 8 March 2024 / Online: 8 March 2024 (09:25:11 CET)

A peer-reviewed article of this Preprint also exists.

Rodríguez-Rivera, N.S.; Barrera-Oviedo, D. Exploring the Pathophysiology of ATP-Dependent Potassium Channels in Insulin Resistance. Int. J. Mol. Sci. 2024, 25, 4079. Rodríguez-Rivera, N.S.; Barrera-Oviedo, D. Exploring the Pathophysiology of ATP-Dependent Potassium Channels in Insulin Resistance. Int. J. Mol. Sci. 2024, 25, 4079.

Abstract

Ionic channels are present in eucaryotic plasmatic and intracellular membranes. They coordinate and control several functions. One of the most diverse ionic channels family are the potassium (K) channels. Within this family are the ATP-dependent potassium channels (KATP), which belong to the potassium rectifier channel family. These channels were initially described in heart muscle, yet they are also present in different types of tissues such as pancreatic, skeletal muscle, brain, and vascular and non-vascular smooth muscle. In ß-pancreatic cells, KATP are primarily responsible for maintaining membrane potential and for the depolarization mediated insulin release. KATP density/activity seems to be determinant in physiological the outcome, in pancreatic cells decrease of this density/activity may be related to Insulin resistance (IR). In extra pancreatic tissues KATP relation with IR is beginning to be explored. It is possible that in skeletal muscle, the KATP are involved in insulin dependent glucose recapture and that KATP activation leads to IR. In adipose tissue, KATP containing Kir6.2, could be related to increase in free fatty acids and insulin resistance, therefore, pathological processes leading to a prolonged adipocyte KATP inhibition might promote obesity related to insulin resistance. In central nervous system KATP activation can regulate peripheric glycemia and lead to brain IR which could be a much earlier manifestation of peripheral alterations that lead to the development of pathologies such as obesity and type 2 diabetes mellitus. In this review we aim to discuss the KATP channel characteristics, its relationship to known clinical disorders and the mechanisms and potential relations with peripheral and central insulin resistance.

Keywords

Ionic channels; ATP-dependent potassium channels; Insulin resistance.

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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