Insulin signalling to the kidney in health and disease

Abstract

Ninety-one years ago insulin was discovered, which was one of the most important medical discoveries in the past century, transforming the lives of millions of diabetic patients. Initially insulin was considered only important for rapid control of blood glucose by its action on a restricted number of tissues; however, it has now become clear that this hormone controls an array of cellular processes in many different tissues. The present review will focus on the role of insulin in the kidney in health and disease.

IGF-1 and insulin exert opposite actions on ClC-K2 activity in the cortical collecting ducts

“…The mean values of P o are 0.34 Ϯ 0.04, 0.11 Ϯ 0.02, and 0.24 Ϯ 0.04 in the control, during insulin (100 nM) application, and washout, respectively (n ϭ 7). Activation of insulin receptors may stimulate PI3-K and MAPK intracellular cascades (8). However, we demonstrate that PI3-K-dependent pathway increases ClC-K2 activity in response to IGF-1.…”

“…Insulin and IGF-1 have substantial structural similarity and IGF-1 receptor is also very similar to insulin receptor (16,37). Both receptors possess tyrosine kinase activity and involve activation of PI3-K and MAPK pathways (8). Despite this, insulin and IGF have clearly distinct physiological functions.…”

“…Stimulation of IGF-1 receptors generally leads to activation of a PI3-K-dependent cascade (8). Therefore, we next tested whether inhibition of PI3-K affects regulation of ClC-K2 activity by IGF-1 in CCD cells.…”

“…Insulin and structurally related insulin growth factor-1 (IGF-1) have been long recognized to play a role in controlling renal function (2,8). Both hormones trigger activation of PI3-kinase (PI3-K)-and mitogen-activated protein kinase (MAPK)-dependent pathways via predominant binding to respective insulin and IGF-1 receptors expressed at both apical and basolateral sides along the renal tubule (2,7,8).…”

“…Both hormones trigger activation of PI3-kinase (PI3-K)-and mitogen-activated protein kinase (MAPK)-dependent pathways via predominant binding to respective insulin and IGF-1 receptors expressed at both apical and basolateral sides along the renal tubule (2,7,8). In the CCD, insulin and IGF-1 stimulate ENaC-mediated sodium reabsorption through a PI3-K-dependent mechanism (41).…”