Premium
SYMPOSIUM: Experimental Biology 1995 Role of Mesangial Cell Ion Transport in Glomerular Physiology and Disease: REGULATION OF MESANGIAL CHLORIDE CHANNELS BY INSULIN AND GLUCOSE: ROLE IN DIABETIC NEPHROPATHY
Author(s) -
Ling Brian N
Publication year - 1996
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1996.tb03068.x
Subject(s) - diabetic nephropathy , mesangial cell , endocrinology , insulin , medicine , disease , chloride channel , diabetes mellitus , biology , chemistry , microbiology and biotechnology , kidney
SUMMARY1 In response to vasoactive peptides (e.g. angiotensin II (AngII), vasopressin, endothelin‐1, platelet‐activating factor), glomerular mesangial cell contraction is mediated through activation of a Ca 2+ ‐dependent Cl − conductance that, in turn, promotes membrane depolarization and voltage‐activated Ca 2+ entry. 2 Using patch clamp technology, our laboratory was the first to characterize a candidate Ca 2+ ‐dependent, 4pS Cl − channel that is stimulated by vasoactive peptides in cultured rat mesangial cells. In the absence of extracellular insulin, the activation of Cl − channels by AngII is abolished. We find that Cl − channel sensitivity to intracellular Ca 2+ and the membrane density of AngII receptors is also dependent on the presence of insulin. 3 Our studies also show that high extracellular glucose interferes with mesangial cell IP 3 generation and Cl − channel stimulation. Importantly, we find that the insulin‐dependency of Cl − channels occurs within the range of plasma insulin concentrations observed in normal, obese, hypertensive and diabetic humans (i.e. 1–100μU/mL). Similarly, normal regulation of Cl − channel activity is also modulated by glucose concentrations commonly observed in the plasma of diabetic humans (5–30 mmol/L). 4 There is substantial evidence, both in diabetic humans and animal models, that the provision of insulin and improved glycaemic control corrects or prevents glomerular hyperfiltration. The requirement for normal insulin and glucose levels, for the proper regulation of the 4pS Cl − channel, provides a mechanism for impaired Ca 2+ uptake and contraction observed in glomerular mesangial cells in association with insulin deficiency and hyperglocaemia.