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Insulin-like growth factor I resistance in peripheral tissue but not in liver in streptozotocin-induced diabetic rats. 1995

M Tominaga, and K Yamatani, and M Igarashi, and H Eguchi, and M Daimon, and A Sekikawa, and H Sasaki
Third Department of Internal Medicine, Yamagata University School of Medicine, Japan.

The metabolic effect of recombinant human insulin-like growth factor I (IGF-I) was investigated by the glucose clamp technique in normal rats and streptozotocin-induced diabetic rats, a model of insulin-dependent diabetes mellitus (IDDM), and compared with that of insulin. Glucose uptake by peripheral tissues was stimulated by intravenous administration of IGF-I at rates of from 0.369 to 3.690 nmol/kg/min in a dose dependent manner, with a potency of 1/52 that of insulin estimated on the basis of the ED50 molar ratio in normal rats. In streptozotocin-induced diabetic rats, the maximum effects of IGF-I and insulin were reduced to 72% and 70% of those in normal rats, respectively, indicating the presence of both IGF-I and insulin resistance. Hepatic glucose output in normal rats was suppressed by IGF-I in a dose dependent manner with a weaker potency of 1/99 that of insulin assessed on the basis of the ED50 values. In streptozotocin-induced diabetic rats, a dose-response curve of the suppressive effect of insulin on hepatic glucose output shifted to the right, indicating the presence of hepatic insulin resistance, but a leftward shifting of the suppressive effect of IGF-I on hepatic glucose output was observed. We concluded that the IGF-I effect on peripheral tissue was decreased but that on the liver was rather increased in streptozotocin-induced diabetic rats, in contrast to the resistance of both peripheral tissues and liver to insulin.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007333 Insulin Resistance Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. Insulin Sensitivity,Resistance, Insulin,Sensitivity, Insulin
D007334 Insulin-Like Growth Factor I A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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