glucagon monohydrochloride

Glucagon hydrochloride (Porcine glucagon hydrochloride) is a peptide hormone, produced by pancreatic α-cells. Glucagon hydrochloride stimulates gluconeogenesis[1]. Glucagon hydrochloride decreases the activity of HNF-4[2]. Glucagon hydrochloride increases HNF4α phosphorylation[3].

Research Areas >> Metabolic Disease

Signaling Pathways >> GPCR/G Protein >> Glucagon Receptor

Upon binding to its receptor Gcgr, Glucagon activates cAMP-PKA signaling to stimulate hepatic glucose production (HGP) and cause hyperglycemia[1]. Glucagon stimulates both hepatic kisspeptin1 production and gluconeogenesis[1]. Glucagon (100 nM) represses CYP7A1 mRNA expression in human primary hepatocytes[3]. Glucagon (100 nM) increases phosphorylayion of HNF4α[3]. Western Blot Analysis[3] Cell Line: Human primary hepatocytes (H1211, HH1215) Concentration: 100 nM Incubation Time: Result: Resulted in a marked increase in the amount of phosphorylated HNF4α.

Low-dose (20 μg/kg) Glucagon increases glycemia and does not stimulate insulin secretion in ambient-fed mice. High-dose (1 mg/kg) Glucagon lowers glycemia compared with PBS control and stimulates insulin secretion in ambient-fed mice[4]. Animal Model: C57BL/6J mice (12- to 24-week-old)[4] Dosage: 20 μg/kg and 1 mg/kg Administration: Administered by i.p. injection; 45 minutes Result: Low-dose (20 μg/kg) increased glycemia and did not stimulate insulin secretion. High-dose (1 mg/kg) lowered glycemia and stimulated insulin secretion.

[1]. Song WJ, et al. Glucagon regulates hepatic kisspeptin to impair insulin secretion. Cell Metab. 2014 Apr 1;19(4):667-81.

[2]. Hirota K, et al. Hepatocyte nuclear factor-4 is a novel downstream target of insulin via FKHR as a signal-regulated transcriptional inhibitor. J Biol Chem. 2003 Apr 11;278(15):13056-60.

[3]. Song KH, et al. Glucagon and cAMP inhibit cholesterol 7alpha-hydroxylase (CYP7A1) gene expression in humanhepatocytes: discordant regulation of bile acid synthesis and gluconeogenesis. Hepatology. 2006 Jan;43(1):117-25.

[4]. Capozzi ME, et al. Glucagon lowers glycemia when β-cells are active. JCI Insight. 2019 Jul 23;5. pii: 129954.