Insulin rapidly decreases insulin-like growth factor-binding protein-1 gene transcription in streptozotocin-diabetic rats

Mol Endocrinol. 1992 Dec;6(12):2219-28. doi: 10.1210/mend.6.12.1283442.

Abstract

Insulin-like growth factor-binding protein-1 (IGFBP-1) can inhibit or potentiate IGF action. The biological activity of IGFBP-1 is determined by many factors, including its abundance in tissues and plasma, posttranslational modifications, and localization. IGFBP-1 levels in human plasma are highly regulated. They are increased after acute fasting and in diabetes, and are rapidly reversed by refeeding and insulin treatment, respectively. Similarly, IGFBP-1 mRNA is increased in the liver of severely diabetic and ketotic rats and decreased after 4 days of insulin treatment. Insulin rapidly decreases IGFBP-1 mRNA and IGFBP-1 transcription in rat hepatoma cells. The present study asks whether the increase in IGFBP-1 mRNA in diabetic rat liver reflects increased gene transcription, whether insulin decreases IGFBP-1 mRNA through a transcriptional or posttranscriptional mechanism, and whether this decrease is sufficiently rapid to account for the dynamic fluctuations in plasma IGFBP-1. Rats were injected ip with 100 mg/kg streptozotocin and used 7 days later when they were hyperglycemic and failed to gain weight, but were not ketotic. Hepatic IGFBP-1 mRNA levels were 13.6 +/- 5.3-fold greater in diabetic than control liver and decreased to the low levels in nondiabetic controls within 1 h after insulin treatment. In run-on transcription assays, IGFBP-1 transcription was 12.6 +/- 1.5-fold greater in nuclei from diabetic than control liver and decreased to low control levels by 1 h after insulin injection. Normalization of hepatic IGFBP-1 mRNA in insulin-treated diabetic animals did not require restoration of euglycemia. IGFBP-1 mRNA and IGFBP-1 gene transcription also were increased in the kidney of diabetic ketotic rats. We propose that the dynamic regulation of IGFBP-1 gene transcription in diabetes and after insulin treatment, by determining the availability of IGFBP-1 in tissues and plasma, may be a critical factor in the modulation of IGF action.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Blood Glucose / analysis
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Consensus Sequence
  • Depression, Chemical
  • Diabetes Mellitus, Experimental / metabolism*
  • Gene Expression Regulation / drug effects
  • Insulin / pharmacology*
  • Insulin-Like Growth Factor Binding Protein 1
  • Kidney / metabolism
  • Liver / metabolism
  • Male
  • Molecular Sequence Data
  • Rats
  • Rats, Sprague-Dawley
  • Regulatory Sequences, Nucleic Acid
  • Streptozocin
  • Transcription, Genetic / drug effects*

Substances

  • Blood Glucose
  • Carrier Proteins
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 1
  • Streptozocin