Islet prohormone processing in health and disease.
Level 5 - mechanism / opinion, no new human data
Narrative review of islet physiology and genetics without primary clinical or cohort data
PubMed 30230179 · doi:10.1111/dom.13401
What was done
This narrative review synthesizes evidence on the biosynthesis and enzymatic cleavage of pancreatic islet prohormones (proinsulin, proIAPP, and proglucagon) by prohormone convertases (PC1/3, PC2), carboxypeptidase E, and peptidyl-glycine α-amidating monooxygenase (PAM), examining how genetic variation and diabetogenic stress alter these pathways in type 1 and type 2 diabetes.
What was found
The abstract provides no quantitative data or numerical estimates. It notes that genome-wide association studies link processing enzyme genes to obesity, β-cell dysfunction, and type 2 diabetes. Under metabolic or inflammatory stress, elevated proinsulin-to-insulin ratios emerge as markers of β-cell dysfunction, impaired proIAPP processing contributes to diabetes pathogenesis, and α-cells may alter convertase expression (expressing PC1/3) to produce GLP-1(7-36 NH2) rather than mature glucagon.
Why it matters
Clarifying how convertase dysfunction and defective posttranslational modifications impair islet hormone production helps identify potential targets to restore β- and α-cell function in diabetes.
Limits
As a narrative review, it lacks a systematic literature search methodology, quality assessment of cited studies, or quantitative meta-analysis. The abstract provides purely qualitative descriptions and reports no primary human trial or experimental data.
Cited by
- supports Prohormone convertase 1 is the enzyme responsible for cleaving C-peptide from the proinsulin molecule to form mature insulin.