Insulin Infusion Is Linked to Increased <i>NPPC</i> Expression in Muscle and Plasma C-type Natriuretic Peptide in Male Dogs

Gregory, Justin M.; Kraft, Guillaume; Farmer, Ben; Smith, Marta S.; LaNeve, David C.; Williams, Phillip E.; Tomasek, Kelsey; Su, Yan; Wilson, Christopher; Thompson, Mark D.; Cherrington, Alan D.; Coate, Katie C.

doi:10.1210/jendso/bvab088

Cited by 5 publications

(2 citation statements)

References 34 publications

(27 reference statements)

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“…Bulk RNA sequencing (RNA-seq) was performed as described previously (22). Briefly, nucleic acid extraction and purification was performed on 9 canine liver biopsies collected under a steady-state conditions at the end of the 4h experimental period (n=3 each from CTR, GLU, and GGN+GLU groups).…”

Section: Methodsmentioning

confidence: 99%

Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog

Coate,

Ramnanan,

Smith

et al. 2023

Preprint

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Glucagon rapidly and profoundly simulates hepatic glucose production (HGP), but for reasons which are unclear, this effect normally wanes after a few hours, despite sustained plasma glucagon levels. This study characterized the time course and relevance (to metabolic flux) of glucagon-mediated molecular events in the livers of conscious dogs. Glucagon was either infused into the hepato-portal vein at a 6-fold basal rate in the presence of somatostatin and basal insulin, or it was maintained at a basal level in control studies. In one control group glucose remained at basal while in the other glucose was infused to match the hyperglycemia that occurred in the hyperglucagonemic group. Elevated glucagon caused a rapid (30 min) but only partially sustained increase in hepatic cAMP over 4h, a continued elevation in G6P, and activation and deactivation of glycogen phosphorylase and synthase activities, respectively. Net hepatic glycogenolysis and HGP increased rapidly, peaking at 30 min, then returned to baseline over the next three hours (although glucagon’s stimulatory effect on HGP was sustained relative to the hyperglycemic control group). Hepatic gluconeogenic flux did not increase due to lack of glucagon effect on substrate supply to the liver. Global gene expression profiling highlighted glucagon-regulated activation of genes involved in cellular respiration, metabolic processes, and signaling, and downregulation of genes involved in extracellular matrix assembly and development.

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Section: Methodsmentioning

confidence: 99%

Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog

Coate,

Ramnanan,

Smith

et al. 2023

Preprint

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“…A murine study reported that exogenous GLP-1 in pharmacological doses could stimulate ANP expression ( 113 ). In a canine study, insulin infusion increased CNP expression in plasma and skeletal muscle, indicating that a loss of insulin sensitivity could lead to a state of CNP deficiency ( 114 ). Nevertheless, such findings have not been reported in healthy humans or in patients with type 2 diabetes ( 115-117 ).…”

Section: Obesitymentioning

confidence: 99%

A State of Natriuretic Peptide Deficiency

et al. 2022

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Measurement of natriuretic peptides (NPs) has proven its clinical value as biomarker, especially in the context of heart failure (HF). In contrast, a state partial NP deficiency appears integral to several conditions in which lower NP concentrations in plasma presage overt cardiometabolic disease. Here, obesity and type 2 diabetes have attracted considerable attention. Other factors – including age, sex, race, genetics, and diurnal regulation – affect the NP “armory” and may leave some individuals more prone to development of cardiovascular disease. The molecular maturation of NPs has also proven complex with highly variable O-glycosylation within the biosynthetic precursors. The relevance of this regulatory step in post-translational propeptide maturation has recently become recognized in biomarker measurement/interpretation and cardiovascular pathophysiology. An important proportion of people appear to have reduced effective net NP bioactivity in terms of receptor activation and physiological effects. The state of NP deficiency, then, both entails a potential for further biomarker development and could also offer novel pharmacological possibilities. Alleviating the state of NP deficiency before development of overt cardiometabolic disease in selected patients could be a future path for improving precision medicine.

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Neuromuscular and gene signaling responses to passive whole-body heat stress in young adults

Yen,

Petrie,

Suneja

et al. 2023

Journal of Thermal Biology

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Insulin Infusion Is Linked to Increased NPPC Expression in Muscle and Plasma C-type Natriuretic Peptide in Male Dogs

Cited by 5 publications

References 34 publications

Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog

Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog

A State of Natriuretic Peptide Deficiency

Neuromuscular and gene signaling responses to passive whole-body heat stress in young adults

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