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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rate of glucose-stimulated insulin release was found to be increased but that of proinsulin conversion decreased in islets removed from diazoxide-treated rats. This coincided with an elevated islet proinsulin/insulin ratio. The defect in proinsulin conversion was not corrected by preincubating the islets, at high glucose concentration, in the presence of either urokinase or rat serum. Likewise, the administration of kallikrein inhibitor in vivo did not affect the rate of proinsulin conversion as measured in vitro. Since these results fail to document a role for exocytosis-coupled endocytotic uptake of circulating factors in the efficiency of proinsulin conversion, it is speculated that the slackening of the latter process in islets removed from diazoxide-treated rats could be somehow linked to sustained inhibition of insulin release.
Diabetes Res 1989 Feb
PMID:Diazoxide-induced long-term hyperglycemia. II. Slackening of proinsulin conversion. 266 20

Essential hypertension (EH) is frequently not only a coexistent, but a preexistent condition in type-II-diabetes mellitus (NIDDM). Possible reasons for this phenomenon include the presence of the insulin resistance/hyperinsulinaemia syndrome in EH, leading to sodium retention, stimulation of the sympathetic nervous system and impaired glucose tolerance. Another reason could be a defect in the kallikrein-kinin system (KKS) which is known to be involved in both the regulation of blood pressure and insulin sensitivity of peripheral tissues. The classical concept of the glandular KKS as being an endocrine system with circulating hormones causing increased renal and peripheral blood flow, hypotension and natriuresis has changed recently, since kallikrein-like activity or mRNA coding for tissue kallikreins were detected in various tissues including kidney, vascular wall and skeletal muscle. This led to the present view, that paracrine local actions of different tissue KKS on regional blood flow, local substrate metabolism and insulin action are probably more important than previously expected. A disorder in the activity of the renal KKS has been known to be present in both NIDDM and EH. Recent work yielded evidence, that skeletal muscle KKS is activated upon muscle work in metabolically healthy subjects, but not in NIDDM and not in the majority of patients with EH. This suppressed tissue KKS seems to be a common feature of EH and NIDDM and might be involved in the pathogenesis of insulin resistance, impaired glucose tolerance and hypertension.
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PMID:The kallikrein/kinin system in the pathogenesis of hypertension in diabetes mellitus. 269 48

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

To determine the role of the kallikrein-kinin (KK) system in patients with diabetes mellitus in relation to nephropathy and/or hypertension, the single-dose effects of captopril (25 mg, p.o.) were examined in 9 control subjects and 32 diabetics (group 1; 11 normotensives without nephropathy, group 2;10 hypertensives without nephropathy, group 3; 11 hypertensives with nephropathy). Significant hypotensive effects of captopril were found in groups 1 and 2 as well as in the control group, but not in group 3. These hypotensive effects were completely blocked by the infusion of ethyl-p-(6-guanidinohexanoyloxy) benzoate methanesulfonate (FOY), a kallikrein inhibitor. The administration of captopril during vehicle infusion induced a significant elevation of plasma renin activity (PRA) at 60 and 120 min after captopril in each group, except for group 3. FOY cancelled these captopril-induced effects on PRA in those groups. No correlation was found between pretreatment PRA and the changes in mean blood pressure (MBP) after captopril during vehicle infusion in whole diabetics. In addition, the daily urinary excretion of kallikrein in group 3 was significantly lower than that in groups 1 and 2 as well as in the control group. These results suggest that the hypotensive action of captopril in diabetics without nephropathy may be largely due to activating the KK system, and that the KK system may be suppressed in hypertensive diabetics with nephropathy.
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PMID:The hypotensive effect of single-dose captopril in diabetics. 309 4

Renal Kallikrein, an enzyme of the distal tubule acting through kinin liberation, may participate to the control of renal circulation and blood pressure. To study if an impairment of its secretion may exist in diabetics, a cross-sectional study was carried out on 40 non-hypertensive and 29 hypertensive diabetics, compared to 30-age related controls. Urinary Kallikrein Activity (UKA) was measured by its kininogenase activity with and without trypsin preincubation. Compared to UKA in controls (86 +/- 9 micrograms lysyl-bradykinin [LBK] produced per minute of incubation), UKA was significantly reduced either in non-hypertensive diabetics (59 +/- 8 micrograms LBK. min.-1; p less than 0.05) and in hypertensive diabetics (26 +/- 6 micrograms LBK. min.-1; p less than 0.001). The ratio of total/active urinary kallikrein was similar in diabetics and in controls. The decline of UKA in diabetics was related to the duration of their disease (r = -0.38; p less than 0.05) and to their stage of retinopathy (r = -0.46; p less than 0.001). UKA values were proportional to creatinine clearance in diabetics (r = 0.58; p less than 0.001). The lowest UKA values were found in patients with a high urinary excretion of albumin (above 500 mg/day): 8 +/- 2 micrograms LBK. min-1 (p less than 0.001) and beta-2-microglobulin (above 382 micrograms/day): 12 +/- 4 micrograms LBK. min-1 (p less than 0.001). These findings support that an impaired secretion of renal kallikrein in diabetics can be related to the duration of diabetes and to the severity of microangiopathy.
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PMID:[Reduction of urinary kallikrein in hypertensive diabetics]. 309 98

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 effects of streptozotocin (STZ) diabetes and insulin on regulation of renal kallikrein were studied in the rat. 1 and 2 wk after STZ injection, diabetic rats had reduced renal levels and urinary excretion of active kallikrein. Tissue and urinary prokallikrein levels were unchanged, but the rate of renal prokallikrein synthesis relative to total protein synthesis was reduced 30-45% in diabetic rats. Treatment of diabetic rats with insulin prevented or reversed the fall in tissue level and excretion rate of active kallikrein and normalized prokallikrein synthesis rate. To further examine insulin's effects, nondiabetic rats were treated with escalating insulin doses to produce hyperinsulinemia. In these rats, renal active kallikrein increased. Although renal prokallikrein was not increased significantly by hyperinsulinemia, its synthesis was increased. As this was accompanied by proportionally increased total protein synthesis, relative kallikrein synthesis rate was not changed. Excretion of active kallikrein was unchanged, but prokallikrein excretion was markedly reduced. Therefore, increased tissue active kallikrein seen with hyperinsulinemia can be explained not only by increased synthesis but also by retention and increased activation of renal prokallikrein. These studies show that STZ diabetes produces an impairment in renal kallikrein synthesis and suggest that this disease state also impairs renal prokallikrein activation. The findings also suggest that insulin modulates renal kallikrein production, activation, and excretion.
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PMID:Abnormal regulation of renal kallikrein in experimental diabetes. Effects of insulin on prokallikrein synthesis and activation. 331 79

Alterations of plasma coagulation factors have been reported in diabetic patients with severe microangiopathy and metabolic derangement. No information is available, however, for well-controlled type-I diabetic patients. Thus, we studied coagulation factors of the contact phase and inhibitors in 80 fairly well-controlled diabetics (42 female, 38 male, age 28 +/- 11 SD years). Mean HbA1c in these patients was 6.6 +/- 1.0 SD, duration of diabetes ranged from 6 months to 30 years, and 36% had retinopathy shown by fluorescein angiography. The well-controlled diabetic patients did not differ from controls in terms of the activity of prekallikrein, factor XII, high molecular weight kininogen, kallikrein inhibitor, C-1-esterase inhibitor and antithrombin III. Only alpha-2-macroglobulin, an inhibitor of the contact phase of blood coagulation, was elevated significantly in these patients (p less than 0.05). Diabetics with retinopathy had similar activities of prekallikrein, factor XII, high molecular weight kininogen, kallikrein inhibitor, c-1-esterase inhibitor and antithrombin III when compared with patients without retinopathy and controls respectively. alpha-2-macroglobulin did not differ in patients with and without diabetic retinopathy but were significantly elevated in both groups compared with controls. Correlation analysis showed significant positive correlation between HbA1c and the activity of high molecular weight kininogen, kallikrein inhibitor and alpha-2-macroglobulin. In patients with poor metabolic control (n = 11; 6 female, 5 male; age 25 +/- 5 SD years; HbA1C 10.7 +/- 0.9) prekallikrein (p less than 0.05), kallikrein inhibitor (p less than 0.005) and alpha-2-macroglobulin (p less than 0.005) were significantly elevated compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1988 Apr
PMID:Coagulation factors of contact phase of haemostasis are normal in well-controlled type-I diabetic patients despite presence of diabetic retinopathy. 340 69

We measured the 24-h excretion of urinary kallikrein in 27 patients with Type 2 (non-insulin-dependent) diabetes and in 10 normal control subjects. Mean (+/- SD) kallikrein excretion in diabetic patients with nephropathy (6.2 +/- 2.4 naphthyl units (NU)/day, n = 13) was significantly lower than in control subjects (12.8 +/- 3.4 NU/day, p less than 0.01) and in diabetic patients without nephropathy (9.4 +/- 3.4 NU/day, n = 14, p less than 0.05). Kallikrein excretion in hypertensive diabetic patients with nephropathy (5.1 +/- 1.6 NU/day, n = 8) was significantly lower (p less than 0.05) than in normotensive patients with nephropathy (8.3 +/- 2.1 NU/day, n = 5). There were no significant differences in kallikrein excretion rate (24-h excretion of urinary kallikrein/24-h creatinine clearance) among control subjects (9.9 +/- 4.3 NU/ml), diabetic patients with (9.0 +/- 3.2 NU/ml) and without (9.3 +/- 3.5 NU/ml) nephropathy. However, kallikrein excretion rate in hypertensive diabetic patients with nephropathy (7.7 +/- 3.3 NU/ml) was significantly lower (p less than 0.05) than in normotensive diabetic patients with nephropathy (11.8 +/- 2.0 NU/ml, n = 10). Respective basal and post-stimulated (with intravenous furosemide 40 mg plus 60 min ambulation) plasma aldosterone concentrations measured in control subjects and in hypertensive diabetic patients with nephropathy were similar and increased to the same extent in the 2 groups (5.5 +/- 3.2 versus 5.3 +/- 3.2 and 9.3 +/- 2.6 versus 10.5 +/- 3.4 ng/ml), although the respective plasma renin activity tended to be lower in diabetic patients than in control subjects (0.7 +/- 0.6 versus 1.3 +/- 0.9 and 1.8 +/- 1.8 versus 3.0 +/- 2.6 ng-1 . ml-1 . h-1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal kallikrein in diabetic patients with hypertension accompanied by nephropathy. 351 73

Urinary prostaglandin (PG) and thromboxane (Tx) excretion, measured by radioimmunoassay, were examined in two groups of male Wistar rats made diabetic with streptozotocin, 70 mg/kg, one of which received daily insulin beginning on the 7th day after administration of streptozotocin. In addition, urinary kallikrein excretion and blood pressure were monitored. After the induction of diabetes the profile of urinary eicosanoid excretion was altered. 6-keto-PGF1 alpha and TxB2 excretion increased markedly within 24 to 48 hr and remained elevated for the duration of the study, up to 58 days. PGF2 alpha excretion also increased, the change being apparent after 6 days whereas PGE2 excretion was reduced at this time. Urinary kallikrein excretion was unchanged but blood pressure became elevated above control levels 2 weeks after the induction of diabetes. Insulin treatment, to maintain mean blood glucose levels below 200 mg/dl, resulted in decreased excretion of TxB2, PGF2 alpha and 6-keto-PGF1 alpha. However, excretion of PGE2 and kallikrein were increased after insulin treatment which also prevented the elevation in blood pressure. These studies indicate that insulin treatment of experimental diabetes corrects alterations in renal arachidonic acid metabolism and prevents the associated increase in blood pressure.
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PMID:Influence of insulin on urinary eicosanoid excretion in rats with experimental diabetes mellitus. 352 18


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