IDENTIFICATION OF HUMAN GLANDULAR KALLIKREIN IN THE BETA-CELL OF THE PANCREAS

To determine the cellular localization of glandular kallikrein in the human pancreas, immunohistochemical studies were performed with a mono-specific antibody against the antigenically identical urinary kallikrein (urokallikrein). The localization of glandular pancreatic kallikrein to the beta cells of the islets was the same as that of insulin in normal human pancreas and in two islet-cell tumors. When beta cells were lacking in islet-cell tumors or in the pancreas of a patient with juvenile-onset diabetes, kallikrein antigen was not detectable. Anti-urokallikrein absorbed with purified urinary or pancreatic kallikrein no longer identified a pancreatic antigen, whereas absorption with insulin had no effect. The beta-cell localization of human pancreatic kallikrein, an endopeptidase that, in concert with carboxypeptidase B, converts bovine proinsulin to a polypeptide with the electrophoretic mobility of insulin, suggests that pancreatic kallikrein may be involved in the physiologic activation of proinsulin. (N Engl J Med 300:1289–1294, 1979) KALLIKREINS, or kininogenases (EC 3.4.21.8), are endopeptidases that generate vasoactive kinin polypeptides from plasma α2-globulin substrates, or kininogens. Kallikreins have been identified in pancreas, salivary glands, sweat, urine and plasma. Glandular kallikreins purified from urine and pancreas have been distinguished from plasma kallikrein by differences in physicochemical properties, synthetic-substrate specificity, amino-terminal residues of the kinin formed, susceptibility to inhibition by various inhibitors1 and lack of antigenic cross-reactivity.2 Glandular kallikreins present in human urine and in pancreatic extracts exhibit antigenic identity when analyzed in Ouchterlony plates with polyspecific antiserum to human pancreas and mono-specific antiserum to human urinary kallikrein. © 1979, Massachusetts Medical Society. All rights reserved.