Coordinate decrease of tissue insulinlike growth factor I posttranscriptiona alternative mRNA transcripts in diabetes mellitus

J. A. Fagin, Charles Roberts, D. LeRoith, A. T. Brown

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Abstract

In these studies, we examined the effect of excess levels of growth hormone (GH) on rat insulinlike growth factor I (IGF-I) gene expression in streptozocin-induced diabetes mellitus. A solution hybridization/RNase protection assay was used to simultaneously quantitate the relative tissue content of the variant IGF-I mRNA species arising from alternative splicing in the region encoding the COOH-terminal extension E-peptide (IGF-Ia and IGF-Ib). IGF-Ia and IGF-Ib mRNAs were markedly decreased in liver, kidney, and lung tissues of diabetic rats. Although GF stimulates IGF-I gene expression, chronic GH excess from implanted somatomammotropic tumors did not appropriately induce tissue IGF-I mRNA content in diabetic animals. Treatment of diabetic rats with insulin for 1 wk restored basal and GH-stimulated IGF-Ia and IGF-Ib mRNA content toward that present in tissues of nondiabetic rats. The ratio of IGF-Ia to IGF-Ib mRNA remained relatively constant for each tissue and was not affected by the diabetic state, chronic GH hyperstimulation, or insulin therapy, suggesting that posttranscriptional splicing is not a regulated event in these conditions. Thus, both circulating IGF-I levels and tissue IGF-I gene expression are profoundly decreased in this model of experimental diabetes. Diminished tissue availability of IGF-I from endocrine and/or paracrine sources may be responsible for the growth retardation seen in uncontrolled diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)428-434
Number of pages7
JournalDiabetes
Volume38
Issue number4
StatePublished - 1989
Externally publishedYes

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Intercellular Signaling Peptides and Proteins
Diabetes Mellitus
Messenger RNA
Gene Expression
Growth Hormone
Insulin
Experimental Diabetes Mellitus
Alternative Splicing
Ribonucleases
Theoretical Models
Kidney
Lung
Liver
Growth
Neoplasms

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Coordinate decrease of tissue insulinlike growth factor I posttranscriptiona alternative mRNA transcripts in diabetes mellitus. / Fagin, J. A.; Roberts, Charles; LeRoith, D.; Brown, A. T.

In: Diabetes, Vol. 38, No. 4, 1989, p. 428-434.

Research output: Contribution to journalArticle

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