Mar 11, 2003

Gelatinase B is diabetogenic in acute and chronic pancreatitis by cleaving insulin

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Francis J DescampsG Opdenakker

Abstract

Genetic, endocrine, and environmental factors contribute to the development of diabetes. Much information has been gathered on the homeostasis mechanisms of glucose regulation by insulin-producing pancreatic beta cells. Here we demonstrate high expression levels of gelatinase B (matrix metalloproteinase-9, MMP-9) by neutrophils in acute pancreatitis and by ductular epithelial cells in chronic pancreatitis. Because gelatinase B processes cytokines and chemokines, we investigated whether and how gelatinase B cleaves insulin. Pure human neutrophil gelatinase B was found to destroy insulin by cleavage at 10 sites. Pancreatic islet and ductular cells are relatively spared in comparison with the complete destruction of acinar cells of the exocrine pancreas in chronic pancreatitis. High expression levels of gelatinase B are maintained in the immediate proximity of insulin-secreting beta cells. Consequently, diabetes may be worsened by enzymatic degradation of insulin by gelatinase B and by the consequent enhancement of the autoimmune process. Gelatinase B is diabetogenic in acute and chronic pancreatitis by cleaving insulin.

  • References23
  • Citations25

References

Mentioned in this Paper

Structure of Beta Cell of Islet
Acute Pancreatitis
Squamous Transitional Epithelial Cell Count
Pancreatitis
Neutrophils as Percentage of Blood Leukocytes (Lab Test)
Cytokinesis of the Fertilized Ovum
Immunocytochemistry
Acute Disease
Chemokine
MMP-9 Activity

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