Kininogen and prekallikrein increases in the blood of streptozotocin-diabetic rats are normalized by insulin in vivo and in vitro

Twelve days following treatment with 50 mg/kg streptozotocin (STZ), male rats were diabetic, with a three-fold increase in blood glucose (P

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Veröffentlicht in:Naunyn-Schmiedeberg's archives of pharmacology 1999-08, Vol.360 (2), p.217-220
Hauptverfasser: Rothschild, A M, Melo, V L, Reis, M L, Foss, M C, Gallo, Jr, L
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container_title Naunyn-Schmiedeberg's archives of pharmacology
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creator Rothschild, A M
Melo, V L
Reis, M L
Foss, M C
Gallo, Jr, L
description Twelve days following treatment with 50 mg/kg streptozotocin (STZ), male rats were diabetic, with a three-fold increase in blood glucose (P
doi_str_mv 10.1007/s002109900068
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Administration of a single dose (10 U/kg i.v.) of regular insulin decreased plasma HK and LK to near non-diabetic values. Within 24 h these values had returned to levels characteristic of uncorrected diabetes. Prekallikrein (PK), the precursor of plasma kallikrein, an enzyme which releases BK from HK, was increased by 63.4% (P<0.05) in STZ-diabetes, but dropped to near normal levels following insulin treatment. Incubation of whole blood of normal or diabetic rats with 0.02-0.2 mU/ml regular insulin for 10 min at 37 C, decreased HK (P<0.01) and PK (P<0.05) and led to the appearance (P<0.05) of Arg-Pro-Pro-Gly-Phe, a partially stable product of BK metabolism, detected in the incubation media by an enzyme-linked immunosorbent assay (ELISA). Incubation of cell-free plasma insulin had no effect on these parameters, suggesting that blood cells, possibly neutrophils, are required by insulin for the activation of plasma PK to kallikrein leading to BK release. 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Administration of a single dose (10 U/kg i.v.) of regular insulin decreased plasma HK and LK to near non-diabetic values. Within 24 h these values had returned to levels characteristic of uncorrected diabetes. Prekallikrein (PK), the precursor of plasma kallikrein, an enzyme which releases BK from HK, was increased by 63.4% (P<0.05) in STZ-diabetes, but dropped to near normal levels following insulin treatment. Incubation of whole blood of normal or diabetic rats with 0.02-0.2 mU/ml regular insulin for 10 min at 37 C, decreased HK (P<0.01) and PK (P<0.05) and led to the appearance (P<0.05) of Arg-Pro-Pro-Gly-Phe, a partially stable product of BK metabolism, detected in the incubation media by an enzyme-linked immunosorbent assay (ELISA). Incubation of cell-free plasma insulin had no effect on these parameters, suggesting that blood cells, possibly neutrophils, are required by insulin for the activation of plasma PK to kallikrein leading to BK release. 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subjects Anesthesia
Animals
Blood Glucose - metabolism
Bradykinin - blood
Bradykinin - metabolism
Diabetes Mellitus, Experimental - metabolism
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Fasting
In Vitro Techniques
Insulin - pharmacology
Kininogens - blood
Male
Prekallikrein - metabolism
Rats
Rats, Wistar
Time Factors
Trypsin - metabolism
title Kininogen and prekallikrein increases in the blood of streptozotocin-diabetic rats are normalized by insulin in vivo and in vitro
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