TY - JOUR
T1 - Coordinate decrease of tissue insulinlike growth factor I posttranscriptiona alternative mRNA transcripts in diabetes mellitus
AU - Fagin, J. A.
AU - Roberts, C. T.
AU - LeRoith, D.
AU - Brown, A. T.
PY - 1989
Y1 - 1989
N2 - 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.
AB - 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.
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U2 - 10.2337/diabetes.38.4.428
DO - 10.2337/diabetes.38.4.428
M3 - Article
C2 - 2925006
AN - SCOPUS:0024520735
SN - 0012-1797
VL - 38
SP - 428
EP - 434
JO - Diabetes
JF - Diabetes
IS - 4
ER -