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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

Kinin system was investigated in 82 patients suffering from diabetes mellitus of various severity. To make pathogenetically substantiated pharmacological correction of the kinin system activity prodectin--kinin antagonist--was used in these patients. A conclusion was drawn that the blood plasma kinin system was activated in the patients with moderately severe and severe diabetes. The activity of total kallikrein and kininogen became normal against the background of prodectin treatment. The blood plasma kinin system activity was normalized simultaneously with the improvement of the diabetic angiopathies course.
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PMID:[Plasma kinin system indices in diabetes mellitus patients before and after treatment with prodectin]. 72 71

Animal models and humans with glomerular hyperfiltration and hyperperfusion secondary to diabetes or high protein diet show increased renal production of kallikrein and kinins. Acute aminoacid infusion or ingestion also raises GFR, RPF and urinary kinins. Treatment with aprotinin or a kinin receptor antagonist reverses or prevents hyperfiltration in these rat models.
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PMID:Renal hyperfiltration states: relationship to kallikrein and kinins. 128 77

To investigate the status of urinary kallikrein excretion (UKE) in patients with non-insulin-dependent diabetes mellitus (NIDDM), we measured UKE in 31 NIDDM patients. They ranged in age from 40 to 70 years (mean, 54.3 +/- 7.8 years), comprising 18 males and 13 females. Their creatinine clearance (Ccr) was 91.6 +/- 5.5 mL/min, and the daily excretion rate of protein was 1.15 +/- 0.72 g/24 hours. Twenty-five normal persons, aged from 37 to 63 years (mean, 51.7 +/- 8.2 years), comprising 14 males and 11 females, were enrolled as controls. The NIDDM patients were further divided into two groups. Group A (n = 21) had regular blood sugar control, while Group B (n = 9) had poor blood sugar control. The autonomic nervous function was tested in 15 patients to study its relationship with UKE. UKE was measured by spectrophotometric assay of the kallikrein enzymatic product on the synthetic substrate S-2266. Autonomic function was evaluated by cardiovascular reflex tests. The results showed that UKE was elevated in Group B, but depressed in Group A (normal vs A vs B: 9.6 +/- 1.0 vs 4.8 +/- 0.9 vs 14.4 +/- 2.7 nkat/24 hours). The UKE/Ccr ratio was similarly elevated in Group B and reduced in Group A (normal vs A vs B: 0.1 +/- 0.01 vs 0.05 +/- 0.01 vs 0.18 +/- 0.04 nkat. mL/day.minute). There was no significant correlation between UKE or the UKE/Ccr ratio and the Valsalva ratio, the 30:15 ratio, or postural blood pressure change. These results suggest that NIDDM patients have abnormal urinary kallikrein excretion levels that are influenced by blood sugar control. The abnormal UKE/Ccr ratio suggests that intrarenal abnormality in the renal kallikrein-kinin system exists in NIDDM patients.
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PMID:Urinary kallikrein excretion in non-insulin-dependent diabetes mellitus. 136 Mar 4

Glomerular filtration rate, renal plasma flow, renal tubular sodium reabsorption (derived from lithium clearance) and renal excretion rates of kallikrein, prostaglandin E2 and systemic and renally-derived metabolites of prostacyclin and thromboxane A2 were measured in patients with Type 1 (insulin-dependent) diabetes mellitus and in normal subjects. Diabetic patients with glomerular hyperfiltration had greater active kallikrein and prostaglandin E2 excretion than patients with normal glomerular filtration rate or than normal control subjects. Both active kallikrein and prostaglandin E2 excretion correlated directly with glomerular filtration rate. Active kallikrein excretion correlated directly with the reabsorption of sodium in the distal tubule. The excretion rates of 6-keto prostaglandin F1 alpha, 2,3 dinor 6-keto prostaglandin F1 alpha, thromboxane B2, 2,3 dinor thromboxane B2 and 11-dehydro thromboxane B2 excretion were not different between the groups. This study confirms in man our previous finding of increased renal kallikrein production in the hyperfiltering streptozotocin-diabetic rat model. Given that kinins generated by kallikrein are extremely potent vasodilators and stimulate the renal production of eicosanoids that also regulate glomerular function, our findings suggest that increased kallikrein activity and prostaglandin E2 production may contribute to renal vasodilatation and hyperfiltration in human diabetes. The localization of kallikrein in the distal connecting tubule makes it plausible that altered sodium transport in the distal tubule may be a signal to increase generation of kallikrein.
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PMID:Renal excretion of kallikrein and eicosanoids in patients with type 1 (insulin-dependent) diabetes mellitus. Relationship to glomerular and tubular function. 139 81

The kallikrein-kinin system was studied in 9 normals, healthy subjects (6 men, 3 women, age range 1 to 14 years) and 15 diabetic patients (9 men, 6 women age range 2 to 14 years) with an evolution of the disease between 1 to 14 years. Diabetic patients with low microalbuminuria (6.62 +/- 0.97 mg/24 h) show increased total and pre-kallikrein respect to control (3 and 2 fold respectively). On the other hand patients with high microalbuminuria (44.7 +/- 13.2 mg/24 h) show a total and pre-kallikrein of more than 4 and 8 fold increased respectively, compare with the control. According with these results we can concluded: 1) The total kallikrein and pre-kallikrein is increased in the diabetic state. 2) When microalbuminuria is high, the total and pre-kallikrein correlates with those increasing. 3) These changes could modified the renal hemodynamic in diabetes.
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PMID:The kallikrein-kinin system in early state of diabetes. 146 65

We previously showed that renal prokallikrein synthesis is reduced in streptozotocin (STZ)-diabetic rats. Plasma renin activity is also reduced in diabetic rats. To investigate the molecular mechanisms underlying these changes, we examined the effects of diabetes and insulin treatment on renal kallikrein and renal renin mRNA levels and the activities of these enzymes. Rats made diabetic by STZ were either treated with 1.5 to 1.75 U PZI insulin daily to maintain moderate hyperglycemia (plasma glucose 200 to 300 mg/dl, D + I) or left untreated to produce severe hyperglycemia (plasma glucose greater than 400 mg/dl, D). Control (C) rats were also studied. After three weeks, renal kallikrein mRNA was reduced 50% in D rats. A proportional reduction in immunoreactive kallikrein was also observed (37.8 +/- 2.5 vs. 55.8 +/- 6.8 ng/mg protein, D vs. C, P less than 0.001). Kallikrein mRNA and immunoreactive kallikrein levels in D + I rats were not different from C rats. Renin mRNA level was also markedly reduced in D rats, compared to C rats. This was associated with reduced plasma renin concentration (4.5 +/- 0.2 vs. 10.5 +/- 1.6 ng Ang I/ml/hr, D vs. C, P less than 0.01). However, renal renin concentration was unchanged (0.84 +/- 0.17 vs. 0.84 +/- 1.3 micrograms Ang I/mg protein/hr, D vs. C). In D + I rats, renin mRNA level and plasma renin concentration were not different from C levels. However, renal renin concentration was increased (1.49 +/- 0.27 micrograms Ang I/mg protein/hr) compared to C rats (P less than 0.05). beta-actin mRNA levels were unchanged in either diabetic rat group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of diabetes and insulin on expression of kallikrein and renin genes in the kidney. 151 1

The relationship between renal hemodynamic abnormalities and renal kallikrein activity was studied in streptozocin-induced diabetic rats. Diabetic rats were either not treated with insulin and had plasma glucose levels greater than 400 mg/dl (severely hyperglycemic diabetic [SD]) or were treated with 1.5-1.75 U/day protamine zinc insulin and had glucose levels of 200-300 mg/dl (moderately hyperglycemic diabetic [MD]). In SD rats, kidney tissue level and excretion of active kallikrein were reduced after 3 wk compared with age-matched nondiabetic control rats (tissue, 11.7 +/- 1.9 vs. 20.5 +/- 1.8 ng/mg protein, P less than 0.005; urine, 126 +/- 12 vs. 179 +/- 10 micrograms/24 h, P less than 0.005). Despite increased kidney size, renal plasma flow (RPF) was reduced in SD rats (5.38 +/- 0.23 vs. 6.37 +/- 0.20 ml/min, P less than 0.05). Glomerular filtration rate (GFR) was not significantly lower (2.77 +/- 0.60 vs. 3.02 +/- 0.56 ml/min). In MD rats, kidney tissue level and excretion of active kallikrein were increased after 5 wk compared with age-matched nondiabetic control rats (tissue, 28.4 +/- 1.3 vs. 23.3 +/- 1.7 ng/mg protein, P less than 0.05; urine, 289 +/- 16 vs. 196 +/- 13 micrograms/24 h, P less than 0.001). In MD rats, GFR and RPF were increased (3.80 +/- 0.11 and 8.04 +/- 0.17 ml/min, respectively) compared with control rats (3.22 +/- 0.05 and 7.28 +/- 0.09 ml/min, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Mar
PMID:Renal kallikrein and hemodynamic abnormalities of diabetic kidney. 168 83

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

Urinary kallikrein (reliable reflexion of its renal excretion) is studied in a large group of diabetic patients with and without nephropathy (again subdivided following Mogensen stages) and in hypertense non-diabetic patients. It is observed that the urinary excretion of kallikrein is independent of the type of diabetes (insulin or non-insulin dependent). There exists a clear difference in the behaviour of this enzyme, in diabetic patients with and without nephropathy, increasing in the former and decreasing in the latter (p less than 0.001). The decrease in urinary kallikrein is parallel to the existence of diabetic nephropathy with arterial hypertension. Urinary kallikrein in hypertense non-diabetic patients who are not treated with diuretics (furosemide) has a behaviour as in normal controls, but it is much higher in patients treated with captopril, being this finding of great importance since it can suggest new therapeutic approaches to diabetic nephropathy.
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PMID:[Renal kallikrein in diabetic nephropathy]. 178 May 9


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