Potential use of growth hormone receptor antagonist in the treatment of diabetic kidney disease.
Various growth factors have been proposed to be players in the development of diabetic microvascular complications. In particular, growth hormone (GH) and insulin-like growth factors (IGFs) have a long history in diabetes, with measurable effects on the development of diabetic kidney disease in experimental animal models through changes in a complex intrarenal system. Furthermore, new data obtained in knock-out (KO) mice with GH receptor (GHR)/GH-binding protein (GHBP) gene disruption have shown that these animals are protected against diabetes-induced renal changes. The recent development of specific inhibitors of GH action, i.e. specific GHR antagonists (GHRAs), has opened the possibility that this group of inhibitors may be used as therapeutic agents in conditions where GH and IGFs have been suggested to play a pathophysiological role, such as late complications of diabetes. Accordingly, new data from studies in diabetic mice treated with a GHRA (G120K-PEG) from the onset of diabetes, showed normalization of the diabetes-associated renal hypertrophy and glomerular enlargement and, most importantly, a lowering effect on the diabetes-induced rise in urinary albumin excretion (UAE), a marker of renal damage. In addition, late intervention with GHRAs alone or in combination with angiotensin-converting enzyme inhibitors in non-obese diabetic mice with manifest renal changes, showed regression in some of the diabetes-associated renal changes (e.g. UAE and renal hypertrophy). These experimental data strongly suggest that GHR blockade may present a new concept in the treatment of diabetic renal complications. Future studies are warranted to characterize fully the clinical potential of GHRAs as drugs for treatment of diabetic complications in general.
Flyvbjerg
A
A
Medical Department M (Diabetes and Endocrinology), Institute of Experimental Clinical Research, University of Aarhus, Aarhus Kommunehospital, Denmark. allan.flyvbjerg@dadlnet.dk
D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors* / Q000235:genetics
C119223:G120K-PEG; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D011092:Polyethylene Glycols; D007334:Insulin-Like Growth Factor I