Abnormal insulin metabolism by specific organs from rats with spontaneous hypertension
- Stanford Univ. School of Medicine, CA (USA)
Spontaneously hypertensive rats (SHR) have been shown to be both insulin resistant and hyperinsulinemic after oral glucose administration or infusion of exogenous insulin during an insulin suppression test. To determine if this hyperinsulinemia may be due to decreased removal of insulin, the metabolic clearance (k) of insulin was measured in isolated perfused liver, kidney, and hindlimb skeletal muscle from SHR and Wistar-Kyoto (WKY) control rats. The data indicate that the k for insulin removal by liver was similar in SHR and WKY rats, averaging 287 +/- 18 and 271 +/- 10 microliters.min-1.g-1 liver, respectively. In contrast, the k for insulin removal by hindlimbs from SHR was decreased 37% (P less than 0.001) compared with WKY rats (8.6 +/- 0.5 vs. 13.7 +/- 0.7 microliters.min-1.g-1 muscle), and this decrease was not accompanied by decreased binding of insulin to its receptor in plantaris muscle. Although the removal of insulin by glomerular filtration was similar in SHR and WKY rats (653 +/- 64 microliters/min vs. 665 +/- 90 microliters.min-1.kidney-1), total insulin removal by kidney was significantly lower (P less than 0.05) in SHR (710 +/- 78 microliters/min) compared with WKY rats (962 +/- 67 microliters/min), due to decreased peritubular clearance of insulin in SHR (56 +/- 73 vs. 297 +/- 59 microliters/min, P less than 0.05). These findings suggest that the decreased clearance of insulin in SHR rats was possibly not due to impaired hepatic removal of insulin but rather to decreased removal by skeletal muscle and kidneys.
- OSTI ID:
- 5227335
- Journal Information:
- American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 257; ISSN 0002-9513; ISSN AJPHA
- Country of Publication:
- United States
- Language:
- English
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550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL TISSUES
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL VARIABILITY
BLOOD PRESSURE
BODY
CARDIOVASCULAR DISEASES
DIGESTIVE SYSTEM
DISEASES
GENETIC VARIABILITY
GLANDS
HORMONES
HYPERTENSION
INSULIN
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPE DILUTION
ISOTOPES
KIDNEYS
KINETICS
LIVER
MAMMALS
MEMBRANE PROTEINS
METABOLISM
MUSCLES
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PEPTIDE HORMONES
PERFUSED ORGANS
PERFUSED TISSUES
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SYMPTOMS
TISSUES
TRACER TECHNIQUES
VASCULAR DISEASES
VERTEBRATES