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

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.