Expression of the two insulin receptor isoforms is not altered in the skeletal muscle and liver of diabetic rats

Sbraccia, P.; Giaccari, A.; D'Adamo, M.; Caiola, S.; Morviducci, L.; Zorretta, D.; Maroccia, E.; Buongiorno, A.; Tamburrano, G.

Next »Metabolism - Clinical and Experimental
Volume 47, Issue 2 , Pages 129-132, February 1998

Expression of the two insulin receptor isoforms is not altered in the skeletal muscle and liver of diabetic rats☆

P. Sbraccia
- Address reprint requests to P. Sbraccia, MD, PhD, Cattedra di Endocrinologia 1, Clinica Medica 2, Policlinico Umberto 1, Viale del Policlinico, I-00161 Roma, Italy.
- Division of Endocrinology 1, Università “La Sapienza,” Rome, Italy
- Clinical Biochemistry Laboratory, Istituto Superiore di Sanità, Rome, Italy
- Institute of Endocrinology, Catholic University, Rome, Italy
A. Giaccari
- Division of Endocrinology 1, Università “La Sapienza,” Rome, Italy
- Clinical Biochemistry Laboratory, Istituto Superiore di Sanità, Rome, Italy
- Institute of Endocrinology, Catholic University, Rome, Italy
M. D'Adamo
- Division of Endocrinology 1, Università “La Sapienza,” Rome, Italy
- Clinical Biochemistry Laboratory, Istituto Superiore di Sanità, Rome, Italy
- Institute of Endocrinology, Catholic University, Rome, Italy
S. Caiola
- Division of Endocrinology 1, Università “La Sapienza,” Rome, Italy
- Clinical Biochemistry Laboratory, Istituto Superiore di Sanità, Rome, Italy
- Institute of Endocrinology, Catholic University, Rome, Italy
L. Morviducci
- Division of Endocrinology 1, Università “La Sapienza,” Rome, Italy
- Clinical Biochemistry Laboratory, Istituto Superiore di Sanità, Rome, Italy
- Institute of Endocrinology, Catholic University, Rome, Italy
D. Zorretta
- Division of Endocrinology 1, Università “La Sapienza,” Rome, Italy
- Clinical Biochemistry Laboratory, Istituto Superiore di Sanità, Rome, Italy
- Institute of Endocrinology, Catholic University, Rome, Italy
E. Maroccia
- Division of Endocrinology 1, Università “La Sapienza,” Rome, Italy
- Clinical Biochemistry Laboratory, Istituto Superiore di Sanità, Rome, Italy
- Institute of Endocrinology, Catholic University, Rome, Italy
A. Buongiorno
- Division of Endocrinology 1, Università “La Sapienza,” Rome, Italy
- Clinical Biochemistry Laboratory, Istituto Superiore di Sanità, Rome, Italy
- Institute of Endocrinology, Catholic University, Rome, Italy
G. Tamburrano
- Division of Endocrinology 1, Università “La Sapienza,” Rome, Italy
- Clinical Biochemistry Laboratory, Istituto Superiore di Sanità, Rome, Italy
- Institute of Endocrinology, Catholic University, Rome, Italy

Received 30 November 1995; accepted 26 August 1997.

Abstract

Alternative splicing of the 36—base pair exon 11 of the human insulin receptor (IR) gene and of the corresponding domain of the rat IR gene results in the synthesis of two IR isoforms with distinct functional characteristics. Altered expression of these IR isoforms has been previously demonstrated in the skeletal muscle of patients with non—insulin-dependent diabetes mellitus (NIDDM); however, this observation was not confirmed by other studies and is still a matter of debate. To assess whether the reported altered isoform expression is due to the secondary metabolic derangement of diabetes, we examined alternative splicing of IR mRNAs (IR36⁺ and IR36⁻, corresponding to human Ex11⁺ and Ex11⁻) in the skeletal muscle and liver of 6-hour fasting 90% pancreatectomized insulin-resistant diabetic and control Sprague-Dawley rats, using the reverse transcriptase—polymerase chain reaction (PCR) technique. Both diabetic and control rats showed the same pattern of IR mRNA expression: the liver exclusively expressed IR36⁺ mRNA, whereas only IR36⁻ mRNA was detected in muscle. In conclusion, diabetes mellitus per se does not alter the expression of IR isoforms in the liver and skeletal muscle, and therefore, at least in this animal model of NIDDM, impaired insulin action develops independently from a relative increase in IR36⁺ mRNA expression in skeletal muscle.

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☆ Supported by the Eli Lilly/European Association for the Study of Diabetes Research Fellowship in Diabetes and Metabolism (P.S.), the “Istituto Pasteur-Fondazione Cenci Bolognetti” Foundation of the University of Rome (P.S.), a fellowship (393323) from the Juvenile Diabetes Foundation (A.G.), the Centro Internazionale Studi Diabete (G.T.), and the Istituto Superiore di Sanità, Progetto Sindromi Ipoglicemiche, 4.5 (A.B.).

PII: S0026-0495(98)90207-4

Next »Metabolism - Clinical and Experimental
Volume 47, Issue 2 , Pages 129-132, February 1998

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