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

Rothschild, A. M.; Melo, Vidal Augusto Zapparoli Castro; Reis, Marina Lemos dos; Foss, Milton César; Gallo, L.

doi:10.1007/s002109900068

Cited by 11 publications

(6 citation statements)

References 13 publications

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“…This is in agreement with the enhanced vascular permeability attributed to B 1 receptors in several peripheral tissues from type-1 diabetic mice [128]. In this context, it is worth noting that higher circulating levels of high and low molecular weight kininogens and prekallikrein were found in type-1 diabetic rat [129].…”

Section: Diabetessupporting

confidence: 71%

Targeting Kinin Receptors for the Treatment of Neurological Diseases

Rodi

Couture²,

Ongali³

et al. 2005

CPD

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Kinins (bradykinin, kallidin and their active metabolites) are peptide autacoids with established functions in cardiovascular homeostasis, contraction and relaxation of smooth muscles, inflammation and nociception. They are believed to play a role in disease states like asthma, allergies, rheumatoid arthritis, cancer, diabetes, endotoxic and pancreatic shock, and to contribute to the therapeutic effects of ACE inhibitors in cardiovascular diseases. Although kinins are also neuromediators in the central nervous system, their involvement in neurological diseases has not been intensively investigated thus far. This review analyzes the potential of central kinin receptors as therapeutic targets for neurological disorders. Initial data highlight potential roles for B(1) receptor antagonists as antiepileptic agents, and for B(2) receptor antagonists (and/or B(1) agonists) in the treatment of stroke. Functional B(1) receptors located on T-lymphocytes and on the blood brain-barrier are also putative targets for the management of multiple sclerosis. However, successful elucidation of the therapeutic value of these new pharmacological approaches will require refinement of our knowledge on the physiology and cellular localization of central kinin receptors.

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Section: Diabetessupporting

confidence: 71%

Targeting Kinin Receptors for the Treatment of Neurological Diseases

Rodi

Couture²,

Ongali³

et al. 2005

CPD

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“…To provide further evidence of the participation of the KKS, we and others observed the development of hypotension in STZ rats over the first 4 weeks post-STZ, in addition to increased circulating plasma concentrations of BK (Campbell et al, 1999;Nantel et al, 2005) and of blood kininogen and prekallikrein (Rothschild et al, 1999). Still, Tschope et al (1999) reported that diabetic rats had a normotensive profile and showed a reduction in the myocardial gene expression of both rat tissue kallikrein 1 and 7 (rKLK1 and rKLK7) 12 weeks post-STZ.…”

Section: Emerging Strategies Against Pdnmentioning

confidence: 90%

The kinin system mediates hyperalgesia through the inducible bradykinin B1 receptor subtype: evidence in various experimental animal models of type 1 and type 2 diabetic neuropathy

Gabra

Berthiaume²,

Sirois

et al. 2006

Biological Chemistry

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Both insulin-dependent (type 1) and insulin-independent (type 2) diabetes are complex disorders characterized by symptomatic glucose intolerance due to either defective insulin secretion, insulin action or both. Unchecked hyperglycemia leads to a series of complications among which is painful diabetic neuropathy, for which the kinin system has been implicated. Here, we review and compare the profile of several experimental models of type 1 and 2 diabetes (chemically induced versus gene-prone) and the incidence of diabetic neuropathy upon aging. We discuss the efficacy of selective antagonists of the inducible bradykinin B1 receptor (BKB1-R) subtype against hyperalgesia assessed by various nociceptive tests. In either gene-prone models of type 1 and 2 diabetes, the incidence of hyperalgesia mostly precedes the development of hyperglycemia. The administration of insulin, achieving euglycemia, does not reverse hyperalgesia. Treatment with a selective BKB1-R antagonist does not affect basal nociception in most normal control rats, whereas it induces a significant time- and dose-dependent attenuation of hyperalgesia, or even restores nociceptive responses, in experimental diabetic neuropathy models. Diabetic hyperalgesia is absent in streptozotocin-induced type 1 diabetic BKB1-R knockout mice. Thus, selective antagonism of the inducible BKB1-R subtype may constitute a novel and potential therapeutic approach for the treatment of painful diabetic neuropathy.

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“…In these patients, insulin administration associated with a test meal reduces the level of high molecular weight kininogen [94]. Similar observations were made in streptozotocin-diabetic rats [95]. In these rats, plasma levels of kininogens and of plasma prekallikrein are elevated.…”

Section: Diabetes Mellitusmentioning

confidence: 63%

“…Injection of insulin reduced plasma kininogens and prekallikrein. Moreover, incubation of insulin with blood of normal or diabetic rats results in a decrease in high molecular weight kininogen and prekallikrein associated with an increase in the blood level of a metabolite of BK [95]. These results suggest that the lack of insulin in diabetes is responsible for an impaired activation of the plasma kallikrein-kinin system.…”

Section: Diabetes Mellitusmentioning

confidence: 76%

The kallikrein‐kinin system, angiotensin converting enzyme inhibitors and insulin sensitivity

Damas

Garbacki

Lefèbvre

2004

Diabetes Metabolism Res

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The therapeutic use of angiotensin converting enzyme (ACE) inhibitors, at a large scale, in arterial hypertension has showed that these molecules can exert beneficial effects on insulin sensitivity and may reduce the occurrence of type 2 diabetes mellitus. One hypothesis explaining these effects of ACE inhibitors may relate to their capacity to interfere with bradykinin (BK) metabolism and action. BK may participate in the regulation of substrate utilization by several tissues by improving blood flow and substrate delivery to the tissues and also by promoting translocation of glucose transporters. Moreover, BK has been shown to increase phosphorylation of insulin receptor and its cell substrates. BK also appears to improve the release of insulin. Furthermore, insulin may activate the kallikrein-kinin system, which consequently may increase its metabolic effects. However, in experimental diabetes mellitus, BK can participate to the inflammatory reaction leading to Langerhans islets destruction. In diabetes, whereas tissue kallikrein mRNA levels were reduced in several organs, an overexpression of kinin receptors, an increase in plasma levels of kininogens and kallikrein and an activation of the kinin system have all been reported. Lastly, kinins may be involved in the development of diabetic nephropathy. Reduction of kinin metabolism by ACE inhibitors might be involved in the beneficial effects exerted by these compounds in diabetic kidney functions.

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

Cited by 11 publications

References 13 publications

Targeting Kinin Receptors for the Treatment of Neurological Diseases

Targeting Kinin Receptors for the Treatment of Neurological Diseases

The kinin system mediates hyperalgesia through the inducible bradykinin B1 receptor subtype: evidence in various experimental animal models of type 1 and type 2 diabetic neuropathy

The kallikrein‐kinin system, angiotensin converting enzyme inhibitors and insulin sensitivity

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