Reduced glomerular angiotensin II receptor density in diabetes mellitus in the rat: time course and mechanism
Glomerular angiotensin II receptors are reduced in number in early diabetes mellitus, which may contribute to hyperfiltration and glomerular injury. The time course and role of the renin-angiotensin-aldosterone system in the pathogenesis of the receptor abnormality were studied in male Sprague-Dawley rats made diabetic with streptozotocin (65 mg, iv). Glomerular angiotensin II receptors were measured by Scatchard analysis; insulin, renin activity, angiotensin II, and aldosterone were measured by RIA. Diabetes mellitus was documented at 24 h by a rise in plasma glucose (vehicle-injected control, 133 +/- 4; diabetic, 482 +/- 22 mg/dl and a fall in plasma insulin (control, 53.1 +/- 5.7; diabetic, 35.6 +/- 4.0 microIU/ml. At 24 h glomerular angiotensin II receptor density was decreased by 26.5% in diabetic rats (control, 75.5 +/- 9.6 X 10(6); diabetic, 55.5 +/- 8.3 X 10(6) receptors/glomerulus. Receptor occupancy could not explain the defect, because there was reduced binding in diabetic glomeruli after pretreatment with 3 M MgCl/sub 2/, a maneuver that caused dissociation of previously bound hormone. There was a progressive return of the receptor density toward normal over the 60 days following induction of diabetes, with diabetic glomeruli measuring 22.7%, 14.8%, and 3.7% fewer receptors than age-matched controls at 11 days, 1 month, and 2 months, respectively.
- Research Organization:
- North Shore Univ. Hospital, Manhasset, NY
- OSTI ID:
- 6520826
- Journal Information:
- Endocrinology; (United States), Vol. 4
- Country of Publication:
- United States
- Language:
- English
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ANGIOTENSIN
BIOCHEMICAL REACTION KINETICS
RADIOIMMUNOASSAY
DIABETES MELLITUS
PATHOGENESIS
ALDOSTERONE
INSULIN
MAGNESIUM
RATS
RECEPTORS
RENIN
ADRENAL HORMONES
ALDEHYDES
ALKALINE EARTH METALS
ANIMALS
CARDIOVASCULAR AGENTS
CORTICOSTEROIDS
DISEASES
DRUGS
ELEMENTS
ENDOCRINE DISEASES
ENZYMES
GLOBULINS
HORMONES
HYDROLASES
HYDROXY COMPOUNDS
IMMUNOASSAY
IMMUNOLOGY
ISOTOPE APPLICATIONS
KETONES
KINETICS
MAMMALS
MEMBRANE PROTEINS
METABOLIC DISEASES
METALS
MINERALOCORTICOIDS
NONSPECIFIC PEPTIDASES
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PEPTIDE HYDROLASES
PREGNANES
PROTEINS
RADIOASSAY
RADIOIMMUNOLOGY
REACTION KINETICS
RODENTS
STEROID HORMONES
STEROIDS
TRACER TECHNIQUES
VASOCONSTRICTORS
VERTEBRATES
550901* - Pathology- Tracer Techniques