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: English
• Published: Dryad 2021
• Subjects: FOS Biological sciences; c-type natriuretic peptide; Diabetes mellitus; Insulin; RNA sequencing; skeletal muscle; Canis lupus
• Online Access: https://dx.doi.org/10.5061/dryad.stqjq2c33; https://datadryad.org/stash/dataset/doi: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 ... : 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 standards of the American Association for the Accreditation of Laboratory Animal Care guidelines. They were fed a 65-75 kcal/kg/day diet of canned meat and chow (28% protein, 49% carbohydrate, and 23% fat) and the protocol was approved by the Vanderbilt University Medical Center Animal Care Committee. Approximately 16 days prior to experiments, a silastic sampling catheter was placed in the femoral artery and a laparotomy was performed to place infusion catheters in the jejunal and splenic veins, which drain into the hepatic portal circulation, as previously described(22). Experimental inclusion criteria included a leukocyte count < 18,000/mm3, hematocrit > 36%, good appetite, normal bowel movements, and healthy physical appearance. Experimental Procedures The dogs were fasted for 18-hours prior to each experiment. On the morning of study, intravenous ...