The role of prohormone convertases in insulin biosynthesis: Evidence for inherited defects in their action in man and experimental animals

D. F. Steiner, Y. Rouillé, Qiuming Gong, S. Martin, R. Carroll, S. J. Chan

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The hormone insulin remains the cornerstone of diabetic therapy since it is required for almost all cases of Type 1 and many cases of Type 2 diabetes. Since the discovery of insulin in 1921, much has been learned about its chemistry, structure and action as well as its production in the β cell. Insulin is formed through a series of precursors, beginning with preproinsulin, the protein encoded in the insulin gene. These precursors direct the prohormone into the secretory pathway and ultimately into the secretory granules where it is converted into insulin and C-peptide. These products are stored and secreted together in a highly regulated manner in response to glucose and other stimuli. This review focuses on the recently discovered prohormone convertases, PC2 and PCS (PC1), the enzymes responsible for the endoproteolytic processing of proinsulin to insulin and C-peptide in the β cell as well as for the selective processing of proglucagon to glucagon in the alpha cell or GLP1 in intestinal L-cells. PC2 and PC3 are calcium-dependent senne proteases related to the bacterial enzyme subtilisin. They cleave selectively at Lys-Arg or Arg-Arg sites in precursors, generating products with C-terminal basic residues that are then removed by carboxypeptidase E, an exopeptidase. All 3 enzymes are expressed mainly in secretory granules of neuroendocrine celles throughout the body and in the brain Inherited defects affecting the prohormone-processing enzymes have recently been found in association with unusual syndromes of obesity and other metabolic disorders.

Original languageEnglish (US)
Pages (from-to)94-104
Number of pages11
JournalDiabetes and Metabolism
Volume22
Issue number2
StatePublished - Apr 1996
Externally publishedYes

Fingerprint

Proprotein Convertases
Insulin
C-Peptide
Secretory Vesicles
Enzymes
arginylarginine
Proprotein Convertase 2
Carboxypeptidase H
Proglucagon
Exopeptidases
Enteroendocrine Cells
Subtilisin
Proinsulin
Secretory Pathway
Glucagon
Type 2 Diabetes Mellitus
Peptide Hydrolases
Obesity
Hormones
Calcium

Keywords

  • Biosynthesis
  • Carboxypeptidase
  • Proglucagon
  • Proinsulin
  • Subtilisin-like protein convertases

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

The role of prohormone convertases in insulin biosynthesis : Evidence for inherited defects in their action in man and experimental animals. / Steiner, D. F.; Rouillé, Y.; Gong, Qiuming; Martin, S.; Carroll, R.; Chan, S. J.

In: Diabetes and Metabolism, Vol. 22, No. 2, 04.1996, p. 94-104.

Research output: Contribution to journalArticle

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