Protection against diabetes-induced nephropathy in growth hormone receptor/binding protein gene-disrupted mice.
To further investigate the role of GH in diabetic nephropathy, experimental diabetes was induced with streptozotocin (STZ) in mice in which the GH receptor/binding protein gene was disrupted. Body weight, blood glucose, and renal histology and morphometry were studied 10 weeks after diabetes induction in wild-type (+/+) mice and in mice heterozygous (+/-) and homozygous (-/-) for the disruption. Equivalent levels of hyperglycemia developed in all diabetic groups. Normal weight gain was absent in +/+ and +/- diabetic groups, and -/- diabetics lost weight during the study. Diabetic +/+ and +/- groups both showed evidence of glomerulosclerosis, increases in glomerular volume, and increases in the ratio of mesangial area to total glomerular area, whereas diabetic -/- mice showed none of these pathological changes. These results extend our previous findings of protection against diabetes-associated kidney damage in transgenic mice expressing a GH antagonist. Taken together, the results argue for an important role of GH in the development of diabetes induced end-organ damage.
Bellush
L L
LL
Edison Biotechnology Institute, College of Osteopathic Medicine, Ohio University, Athens 45701, USA.
Doublier
S
S
Holland
A N
AN
Striker
L J
LJ
Striker
G E
GE
Kopchick
J J
JJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D003929:Diabetic Neuropathies / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005920:Glomerular Mesangium / Q000473:pathology; D007668:Kidney / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000502:physiology; D011986:Receptors, Somatotropin / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D001786:Blood Glucose; D011986:Receptors, Somatotropin