Asprosin, a Fasting-Induced Glucogenic Protein Hormone

Cell. 2016 Apr 21;165(3):566-79. doi: 10.1016/j.cell.2016.02.063. Epub 2016 Apr 14.

Abstract

Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation. Humans and mice with insulin resistance show pathologically elevated plasma asprosin, and its loss of function via immunologic or genetic means has a profound glucose- and insulin-lowering effect secondary to reduced hepatic glucose release. Asprosin represents a glucogenic protein hormone, and therapeutically targeting it may be beneficial in type II diabetes and metabolic syndrome.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue, White / metabolism
  • Amino Acid Sequence
  • Animals
  • Antibodies / administration & dosage
  • Circadian Rhythm
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Fasting / blood
  • Fasting / metabolism*
  • Female
  • Fetal Growth Retardation / metabolism
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Microfilament Proteins / blood
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Molecular Sequence Data
  • Peptide Fragments / blood
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Peptide Hormones / blood
  • Peptide Hormones / chemistry
  • Peptide Hormones / genetics
  • Peptide Hormones / metabolism*
  • Progeria / metabolism
  • Recombinant Proteins / administration & dosage
  • Sequence Alignment

Substances

  • Antibodies
  • Insulin
  • Microfilament Proteins
  • Peptide Fragments
  • Peptide Hormones
  • Recombinant Proteins
  • asprosin protein, human
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Glucose

Supplementary concepts

  • Progeroid syndrome, neonatal