Role of the liver in regulating somatomedin activity: effects of streptozotocin diabetes and starvation on the synthesis and release of insulin-like growth factor and its carrier protein by the isolated perfused rat liver
- Univ. of Rochester School of Medicine and Dentistry, NY
Isolated liver perfusions to examine the effects of experimental diabetes mellitus or starvation on the synthesis/release of somatomedin activity, insulin-like growth factor (IGF), by the liver of adult male Sprague-Dawley rat. Diabetes was induced by the iv injection of streptozotocin (80 mg/kg BW). One group of diabetic liver donors was untreated for 6-8 weeks; a second and third groups of diabetic rats were treated with protamine zinc insulin (2-3 U daily) for periods of 6-8 weeks and 8-9 months, respectively. At the close of these time periods, livers were perfused, and the net cumulative release of IGF and its carrier protein (CP) into perfusates was calculated. The net cumulative synthesis/release of IGF (mean +- SEM, expressed as microunits per 300 cm/sup 2/ body surface area of donor rat) by livers from untreated diabetic rats (116 +- 94) was profoundly decreased to less than 5% of normal 6280 +- 630. Livers from insulin-treated diabetic rats showed significant decreased in IGF production to 57% (6-8 weeks) and about 15% (at 8-9 months) of normal. Synthesis/release of CP was relatively unaffected by diabetes; a small but significant difference from normal became apparent only at 12 h. Livers from otherwise normal 2- to 6-day-starved rats were perfused, and production of IGF and CP was measured; impairment of IGF production was already as severe at 2 days as that in livers from untreated diabetics, while production of CP was impaired only in livers of rats starved from 3-6 days. Severity of diabetes in the liver donors was significantly correlated (P < 0.01) with the net cumulative 12-h production of IGF by the isolated livers. Both decreased hepatic production and serum levels of IGF and its CP in the rat result from diabetes mellitus, and that these changes can be corrected, at least in part, by in vivo insulin administration.
- DOE Contract Number:
- AC02-76EV03490
- OSTI ID:
- 6357318
- Journal Information:
- Endocrinology; (United States), Vol. 108:4
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DIABETES MELLITUS
BIOLOGICAL EFFECTS
FASTING
STH
BIOCHEMICAL REACTION KINETICS
BIOCHEMISTRY
BIOSYNTHESIS
DYNAMIC FUNCTION STUDIES
INSULIN
LIVER
METABOLISM
RATS
ANIMALS
BODY
CHEMISTRY
DIGESTIVE SYSTEM
DISEASES
ENDOCRINE DISEASES
GLANDS
HORMONES
KINETICS
MAMMALS
METABOLIC DISEASES
ORGANS
PEPTIDE HORMONES
PITUITARY HORMONES
REACTION KINETICS
RODENTS
SYNTHESIS
VERTEBRATES
550200* - Biochemistry
551000 - Physiological Systems
550500 - Metabolism