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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1928, Frey and co-workers discovered kallikrein in human urine and described its prolonged hypotensive effect in the dog. Four years later, the same authors first reported a blood glucose-lowering effect of orally administered kallikrein in diabetic patients. However, the observed blood glucose-lowering effect of kallikrein appeared to fade with repeated administration, and therefore its possible metabolic role was not further investigated and fell into disregard. One decade ago, experimental data yielded indirect evidence that the regulation of local skeletal muscle blood flow and glucose uptake during work was mediated by proteolytically cleaved kinins. Further experiments demonstrated that in insulin-resistant states such as postoperative stress and type II diabetes, reduced muscular insulin sensitivity was increased and partly restored by continuous low-dose infusion of synthetic bradykinin. Recent work showing that tissue kallikrein is present in a number of different tissue sites, including skeletal muscle and our own observation of local kinin overflow after muscle work in healthy subjects, but not in type II diabetics, support the concept of a skeletal muscle kallikrein-kinin system (KKS) that is locally activated upon contraction. Moreover, in isolated perfused rat heart preparations, favorable effects of kinins on myocardial glucose uptake, oxidation, and glycolytic flux have been reported. Most interestingly, cardioprotective effects of kinins have been observed and attributed to improved energy and substrate metabolism in ischemic hearts. Taken together, these data gave rise to the concept that tissue KKS might be involved in the local modulation of skeletal muscle and myocardial tissue blood flow and substrate metabolism, and that activation of the KKS is defective in insulin-resistant states.
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PMID:Metabolic effects of kinins: historical and recent developments. 169 62

This article briefly summarizes the historical events particularly these in Japan, in the kallikrein-kinin research and progress of the development of kallidinogenase (INN), enzyme with circulatory action. In 1926, E. K. Frey observed a drop in blood pressure in dogs following intravenous injection of the urine of human and other mammals into dogs. Intensive research showed that the urine contained a high-molecular active substance which dilated the peripheral arterial vessels. The substance was later called kallikrein after the Greek synonym for pancreas, as it occurred there at such a high concentration (Kraut et al., 1930) that this gland was thought to be its cite of origin. In 1930, kallikrein was commercially available as Padutin from Bayer, Germany. The product was introduced into Japan a few years later under the trade name of Kallikrein and was used for the treatment of circulatory disorders even during the Second World War. Kallikrein was again imported by Yoshitomi Pharmaceutical Industries, Ltd. in 1952. However, Kallikrein introduced after the War did not contain substance derived from the urine but from porcine pancreatic kallikrein as the active ingredient. It grew rapidly with its active promotion of the product in such fields as internal medicine, ophthalmology, otology etc. Domestic manufacturers increasingly entered this market and the number of the manufacturing license holders of similar products reached 26 in 1975 when kallidinogenase preparations were designated to undergo drug re-evaluation by the health authorities. Since June 1988 when the re-evaluation for kallidinogenase preparations was completed, all the relevant manufacturers have supplied new formulations containing higher quality substances and labeling their potencies expressed in International Units based on the kallidinogenase reference standards which had since been established.
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PMID:[A review on the development of Kallikrein (Kallidinogenase)]. 1161 17