Insulin infusion is linked to increased NPPC expression in muscle and plasma C-type natriuretic peptide levels in dogs

• Main Authors: Gregory, Justin, Kraft, Guillaume, Farmer, Ben, Smith, Marta, LaNeve, David, Williams, Phillip, Tomasek, Kelsey, Su, Yan Ru, Wilson, Christopher, Thompson, Mark, Cherrington, Alan, Coate, Katie
• Format: Dataset
• Language: unknown
• Published: 2021
• Subjects: c-type natriuretic peptide; Diabetes mellitus; insulin; RNA sequencing; skeletal muscle; Appleby; Canis lupus
• Online Access: https://zenodo.org/record/4618225; https://doi.org/10.5061/dryad.stqjq2c33

The purpose of this study was to assess insulin-stimulated gene expression in canine skeletal muscle with a particular focus on NPPC, the gene that encodes C-type natriuretic peptide, a key hormonal regulator of cardiometabolic function. Four conscious canines underwent hyperinsulinemic, euglycemic clamp studies. Skeletal muscle biopsy and arterial plasma samples were collected under basal and insulin-stimulated conditions. Bulk RNA sequencing of muscle tissue was performed to identify differentially expressed genes between these two steady-state conditions. Our results showed that NPPC was the most highly expressed gene in skeletal muscle in response to insulin infusion, rising fourfold between basal and insulin-stimulated conditions. In support of our RNA-sequencing data, we found that raising the plasma insulin concentration 15-fold above basal elicited a 2-fold (p = 0.0001) increase in arterial plasma concentrations of N-terminal prohormone C-type natriuretic peptide. Our data suggest insulin may play a role in stimulating secretion of C-type natriuretic peptide by skeletal muscle. In this context, C-type natriuretic peptide may act in a paracrine manner to facilitate muscle-vascular bed crosstalk and potentiate insulin-mediated vasodilation. This could serve to enhance insulin and glucose delivery, particularly in the postprandial absorptive state. Funding provided by: National Institute of Diabetes and Digestive and Kidney DiseasesCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000062Award Number: K23DK123392Funding provided by: Juvenile Diabetes Research Foundation United States of AmericaCrossref Funder Registry ID: http://dx.doi.org/10.13039/100008871Award Number: 5-ECR-2020-950-A-NFunding provided by: Appleby Foundation*Crossref Funder Registry ID: Award Number: N/AFunding provided by: Appleby FoundationCrossref Funder Registry ID: Animal Care and Surgical Procedures Four conscious dogs (Canis lupus familiaris) of either sex were studied. Dogs were housed in a facility that met the ...