Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the cellular localization of glandular kallikrein in the human pancreas, immunohistochemical studies were performed with a monospecific 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.
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PMID:Identification of human glandular kallikrein in the beta cell of the pancreas. 22 May 34

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

The renal effects of the prostaglandin synthesis inhibitor naproxen was investigated in eight patients with incipient type I diabetes nephropathy. The patients were treated with 1000 mg naproxen daily for 4 days in a placebo-controlled double-blind cross-over study. Naproxen reduced urinary prostaglandin E2 (PGE2) excretion by 60%, from 276 ng/24 h to 110 ng/24 h (P less than 0.05). Plasma renin activity (PRA) was reduced by 45% (P less than 0.05). Glomerular filtration (GFR) (single bolus 99mTc-DTPA technique) and effective renal plasma flow (ERPF) (131I-Hippuran clearance) were unchanged by naproxen. Microalbuminuria and renal albumin clearance was unchanged as was also urinary excretion of sodium, glandular kallikrein and beta 2-microglobulin (beta 2-M). Our results show that albumin excretion in incipient diabetic nephropathy is not solely dependent on the renal prostaglandin system. The difference in action between naproxen in this study and indomethacin in previous reports, could be caused by renal actions of indomethacin independent of the prostaglandin system.
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PMID:Effects of short-term treatment with naproxen on kidney function in insulin-dependent diabetic patients with microalbuminuria. 181 19

To clarify the relationship between kallikrein-kinin and renin-angiotensin systems, glandular kallikrein, renin and angiotensin converting enzyme in the submandibular gland, the kidney and plasma were investigated in streptozotocin diabetic and spontaneously hypertensive rats. Kallikrein content in the submandibular gland, the kidney and plasma of diabetic rats was found to be decreased compared with nondiabetic controls. Renin activity in diabetic rats was also reduced in the submandibular gland, but the activity showed no significant changes in the kidney and plasma. The activity of angiotensin converting enzyme (ACE) in plasma significantly increased in diabetic rats. On the other hand, kallikrein content in hypertensive rats was depressed in the kidney, while the content was unchanged in the submandibular gland and plasma. Renin activity in hypertensive rats was found to be higher than that of normotensive rats in the submandibular gland, but the activity showed no remarkable changes in the kidney and plasma. ACE activity in plasma markedly decreased in hypertensive rats in contrast to diabetic rats. In hypertensive-diabetic rats, changes in the levels of these enzymes in tested materials were similar to those of diabetic rats. From these results it is reasonable to assume that (1) reduced kallikrein generation and elevated ACE activity may induce impaired kinin formation and contribute to the development of diabetes mellitus apart from the presence of hypertension and (2) low kallikrein content in the kidney could cause hypertension.
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PMID:Glandular kallikrein, renin and angiotensin converting enzyme of diabetic and hypertensive rats. 255 14

The submaxillary gland and kidney of diabetic and hypertensive rats were compared for their content of glandular kallikrein and the activities of tonin and renin. The submaxillary glands and the kidneys of both diabetic Wistar strain and hypertensive rats contained significantly less glandular kallikrein than non-diabetic Wistar strain and hypertensive rats (reduction fron 40 to 76%). The renin activity of the kidney showed only a slight change in spite of diabetes, whereas the activity of the submaxillary gland decreased in parallel with the reduction of the kallikrein content when diabetes was induced. On the other hand, the tonin of the submaxillary gland, which has a potent hypertensive activity like renin, was not affected by induction of diabetes. However, the tonin activity in hypertensive rats was significantly higher (p less than 0.001) than that in the normotensive rats (His-Leu, 168.7 +/- 10.1 vs. 131.5 +/- 17.3 nmol/min X mg protein).
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PMID:Glandular kallikrein, renin and tonin in tissues of diabetic and hypertensive rats. 301 44

A tissue kallikrein was purified from rat skeletal muscle. Characterization of the enzyme showed that it has alpha-N-tosyl-L-arginine methylesterase activity and releases kinin from purified bovine low-Mr kininogen substrate. The pH optimum (9.0) of its esterase activity and the profile of inhibition by serine-proteinase inhibitors are identical with those of purified RUK (rat urinary kallikrein). Skeletal-muscle kallikrein also behaved identically with urinary kallikrein in a radioimmunoassay using a polyclonal anti-RUK antiserum. On Western-blot analysis, rat muscle kallikrein was recognized by affinity-purified monoclonal anti-kallikrein antibody at a position similar to that of RUK (Mr 38,000). Immunoreactive-kallikrein levels were measured in skeletal muscles which have different fibre types. The soleus, a slow-contracting muscle with high mitochondrial oxidative-enzyme activity, had higher kallikrein content than did the extensor digitorum longus or gastrocnemius, both fast-contracting muscles with low oxidative-enzyme activity. Streptozotocin-induced diabetes reduced muscle weights, but did not alter the level of kallikrein (pg/mg of protein) in skeletal muscle, suggesting that insulin is not a regulator of kallikrein in this tissue. Although the role of kallikrein in skeletal muscle is unknown, its localization and activity in relation to muscle functions and disease can now be studied.
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PMID:Identification and characterization of a tissue kallikrein in rat skeletal muscles. 331 Oct 22

The relevance of plasma, glandular and renal kallikrein as an intrarenal hemodynamic regulator, in renal hypertrophy, in 1-5 weeks streptozotocin diabetic rats has been investigated. The fasting plasma glandular kallikrein level significantly decreased with increasing duration of diabetes (p less than 0.05). Glandular kallikrein correlated negatively with kidney weight (r = 0.76, p = 0.05). The 24 hour urinary kallikrein excretion significantly increased with increasing duration of diabetes (p less than 0.05), but this level was not correlated with glucose level, nor with kidney weight. Aprotinin (a kallikrein inhibitor) injected (10 X 10(3) KIU/kg) twice daily for 2 weeks in diabetic rats, significantly decreased plasma glucose levels by 28%, 24 hour urinary kallikrein by 37% (p less than 0.05) and kidney weight by 6%. These results suggest that plasma, glandular and renal kallikrein did not play an important role in the renal hypertrophy observed in streptozotocin diabetic rats.
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PMID:Relevance of plasma, glandular and urinary kallikrein in renal hypertrophy in streptozotocin-diabetic rats. 364 9

Very high blood glucose concentrations were seen in rats one day after injection with alloxan or streptozotocin. Those levels fell (compared to day one, p less than 0.005) by the third day after injection and subsequently rose again during the ensuing days. In contrast, no significant differences between treated and control rats in concentrations of submandibular kallikrein were recorded until the tenth day after the initial injection. At that time the submandibular kallikrein concentrations in the alloxanized and streptozotocinized rats were less (p less than 0.01) than those of the untreated rats. A further fall (compared to day ten, p less than 0.005) took place over the next four days. Thus submandibular kallikrein would not seem to have been involved in the early stages of the experimental diabetes. In agreement with that conclusion were the results of a related series of experiments in which exogenous porcine pancreatic kallikrein was administered to alloxanized rats. The kallikrein did not bring about a reduction in the high blood glucose levels.
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PMID:A study of glandular kallikrein in experimental diabetes. 364 33

Based on a study of the kininogenase activity of the total plasma kallikrein in the presence of 3 concentrations of the soybean inhibitor trypsin (0.5, 1.0, 10.0 micrograms/ml) one can measure at a time the activity of tissue kallikrein (without specifying the source) and the activity of 3 forms of plasma kallikrein, including its adsorption on kaolin that characterizes the conformational structure of the enzyme. Examination of 10 healthy subjects and 136 patients revealed a 10 to 20-fold increase in the content of tissue kallikrein in plasma of 70% of diabetes mellitus patients and a 2.5 to 3-fold elevation in 50% of patients with chronic occupational bronchitis, and in 30% of patients suffering from chronic hepatitis. The method suggested makes it possible to have a better insight into the physiological and pathogenetic role of the kinin system and may be used for laboratory control over the treatment efficacy.
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PMID:[Method for determining kallikrein of tissue origin in blood plasma and its clinical significance]. 384 14

ODU Plaque-susceptible rats (ODUS/Odu) exhibit markedly heavy plaque formation in the lower incisors and develop both periodontal pockets and gingivitis after being fed a commercially available powder diet. These rats have been established as an inbred strain. We have demonstrated that the ODUS/Odu are a very suitable experimental model for studying periodontitis. We already reported about the allelic distribution, changes of plaque formation and body weight, biochemical nature, toxic activity, vascular permeability factor and bradykinin inactivating factor of the plaque, histological and immunological studies, the pH in the periodontal pocket, amount of saliva, IgA in the saliva, salivary kallikrein, the relationship between sialic acid in the saliva and the serum, leukocyte functions (chemotaxis and superoxide anion) in ODUS/Odu, histamine, mast cell, free radicals, superoxide dismutase activities in gingiva and gingival nerve fibers with substance P or calcitonin gene-related peptide, and effect of diabetes. Streptozotocin-induced diabetic ODUS/Odu may be a useful tool for studying the pathological mechanisms in the development of periodontal tissue breakdown in diabetes. ODUS/Odu should help to further establish the utility of this strain as a model for experimental periodontal disease.
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PMID:[Experimental periodontitis in rats]. 762 82


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