Prolonged hyperinsulinemia affects metabolic signal transduction markers in a tissue specific manner

Campolo, A., de Laat, M.A., Keith, L., Gruntmeir, K.J., & Lacombe, V.A. (2016) Prolonged hyperinsulinemia affects metabolic signal transduction markers in a tissue specific manner. Domestic Animal Endocrinology, 55, pp. 41-45.

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Insulin dysregulation is common in horses although the mechanisms of metabolic dysfunction are poorly understood. We hypothesized that insulin signaling in striated (cardiac and skeletal) muscle and lamellae may be mediated through different receptors as a result of receptor content, and that transcriptional regulation of downstream signal transduction and glucose transport may also differ between tissues sites during hyperinsulinemia. Archived samples from horses treated with a prolonged insulin infusion or a balanced electrolyte solution were used. All treated horses developed marked hyperinsulinemia and clinical laminitis. Protein expression was compared across tissues for the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) by immunoblotting. Gene expression of metabolic insulin-signaling markers (insulin receptor substrate 1, Akt2, and glycogen synthase kinase 3 beta [GSK-3β]) and glucose transport (basal glucose transporter 1 and insulin-sensitive glucose transporter 4) was evaluated using real-time reverse transcription polymerase chain reaction. Lamellar tissue contained significantly more IGF-1R protein than skeletal muscle, indicating the potential significance of IGF-1R signaling for this tissue. Gene expression of the selected markers of insulin signaling and glucose transport in skeletal muscle and lamellar tissues was unaffected by prolonged hyperinsulinemia. In contrast, the significant upregulation of Akt2, GSK-3β, GLUT1, and GLUT4 gene expression in cardiac tissue suggested that the prolonged hyperinsulinemia induced an increase in insulin sensitivity and a transcriptional activation of glucose transport. Responses to insulin are tissue-specific, and extrapolation of data across tissue sites is inappropriate.

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ID Code: 91061
Item Type: Journal Article
Refereed: Yes
Keywords: insulin signaling, glucose transporter, laminitis, horse, insulin receptor
DOI: 10.1016/j.domaniend.2015.11.001
ISSN: 0739-7240
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > PHYSIOLOGY (060600) > Animal Physiology - Cell (060602)
Divisions: Current > Schools > School of Earth, Environmental & Biological Sciences
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: Copyright 2015 Elsevier Inc.
Deposited On: 08 Dec 2015 02:14
Last Modified: 30 May 2016 04:50

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