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Query: UMLS:C0011849 (diabetes)
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The urinary bladder and urethral content of substance P and vasoactive intestinal polypeptide and the in vitro effects of the peptides on the bladder were studied at 6 weeks and 6 months of streptozotocin-induced diabetes in the rat. The results were compared with those obtained in age-matched control animals. Both short-term and long-term streptozotocin treatment induced a clearcut increase in bladder weight. Bladder substance P content was increased in both groups of diabetic animals but substance P concentration was similar in control and diabetic animals. Vasoactive intestinal polypeptide content was slightly higher in diabetic animals than in controls but vasoactive intestinal polypeptide concentration was significantly lower in the bladders from both short-term and long-term diabetic animals. The bladder contractile response to substance P was similar in all groups of animals and vasoactive intestinal polypeptide was found to be devoid of contractile or relaxatory effects in the rat bladder. No change in urethral weight was seen with diabetes. There were no clear-cut changes in the urethral contents or concentrations of substance P and vasoactive intestinal polypeptide. The study also enabled comparisons between younger (3 months) and older (9 months) rats. This comparison showed a decrease in the concentrations and contents of substance P and vasoactive intestinal polypeptide between young and older rats. The changes were seen in both the bladder and the urethra and were similar in diabetic and normal animals.
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PMID:Effects of age and streptozotocin-induced diabetes on contents and effects of substance P and vasoactive intestinal polypeptide in the lower urinary tract of the rat. 137 98

Bladder function was investigated in female rats with hereditary diabetes insipidus (DI) and in healthy controls, in vivo by means of recordings of micturition pattern and cystometry, and in vitro in organ bath experiments. Rats with DI exhibited bladder hypertrophy, the weight of the bladder in these rats being two times that of controls. Recordings of micturition pattern showed that DI-rats had an increased 24 hour diuresis and micturition volume, and decreased micturition interval in comparison with controls. Cystometry recordings revealed increased bladder capacity and micturition volume in DI-rats. However, in these rats basal bladder pressure and threshold pressure were lower than in controls. No significant changes in micturition pressure or bladder compliance were observed, and none of the rats had residual urine. In organ bath studies, a lower maximal response to electrical field stimulation was obtained in bladder strips from DI-rats, than in the control strips, when expressed relative to the response elicited by K(+)-solution. When activated by field stimulation, the DI-bladder strips and the control strips had similar sensitivity to muscarinic receptor blockade with scopolamine at all stimulation frequencies. The sensitivity to carbachol was similar in the two groups. The results suggest that the increased functional demands of DI on the detrusor do not result in major changes pre- or postjunctionally. Further, several of the previously reported urinary bladder changes observed in rats with diabetes mellitus (DM) are similar to those now reported in rats with DI, emphasizing the importance of an increased diuresis per se for the development of alterations in bladder function. However, in contrast to the findings in DM rats, the sensitivity to electrical stimulation of nerves during blockade of muscarinic receptors was similar in DI-rats and their controls. This supports our previous suggestion that the increased resistance to muscarinic receptor blockade of the bladder in DM-rats at low stimulation frequencies is induced by the disease (diabetes mellitus) as such and not by the increased diuresis.
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PMID:Urinary bladder function in rats with hereditary diabetes insipidus; a cystometrical and in vitro evaluation. 151 62

Bladder dysfunction is a common complication of diabetes mellitus and is attributed in part to peripheral neuropathy. Voiding function is mainly controlled by muscarinic receptor function. Therefore, I investigated first the biochemical and functional characteristics of urinary bladder muscarinic receptors and then the effects of experimental diabetes on them. Experimental diabetes was induced in 2 month-old male rats by intravenous injection of 65 mg/kg of streptozotocin (STZ). Effects of diabetes mellitus were investigated 2, 4 and 8 weeks after injection of STZ. The amount of muscarinic receptors labelled with 3H-quinuclidinyl benzylate (QNB) was higher in the bladder dome of diabetic animals than control animals, while the affinity for its binding sites was similar in both groups. Muscarinic agonists and antagonists inhibited 3H-QNB binding with similar inhibitory constants (Ki) in control and diabetic domes. The rank order of inhibition of 3H-QNB binding by muscarinic agonists and antagonists: bethanechol greater than pirenzepine greater than carbamylcholine greater than acetylcholine greater than atropine, is consistent with the absence of M1 receptors in the bladder dome. In functional studies muscarinic agonists induced a larger contractile response in bladder dome muscle strips from 8 week-old diabetic animal than those from controls. The rank order of ED50s were similar in the control and treated groups, being in good agreement with the Ki values obtained from receptor binding studies. These data show a direct correlation between the diabetes-induced biochemical and functional alterations in muscarinic receptor properties of the rat bladder.
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PMID:[Biochemical and functional characteristics of bladder muscarinic receptors and effects of experimental diabetes in rats]. 182 10

The urinary bladder depends on intracellular ATP for the support of a number of essential intracellular processes including contraction. The concentration of ATP is maintained constant primarily via the rapid transfer of a phosphate from creatine phosphate (CP) to ADP catalyzed by the enzyme creatine kinase (CK). Since muscular pathologies associated with diabetes are in part related to intracellular alterations in metabolism, we have characterized the CK activity in both skeletal muscle and urinary bladder from control and streptozotocin-diabetic rats. The following is a summary of the results: 1) Bladder tissue from control rats showed linear kinetics with a Vmax = 390 nmoles/mg protein/min, and a Km = 275 microM. 2) Urinary bladder tissue isolated from diabetic rats displayed biphasic kinetics with Vmax = 65 and 324 nmoles/mg protein/min, and Km's = 10 microM and 190 microM respectively. 3) Skeletal muscle isolated from control rats showed linear kinetics with an approximate Vmax of 800 nmoles/mg protein/min and a Km of 280 microM CP. 4) Homogenates of skeletal muscle from diabetic rats showed complex kinetics not separable into distinct component forms. 5) The Km for ADP for both skeletal muscle and bladder was approximately 10 microM. These studies demonstrate that whereas bladders isolated from both control and diabetic rats possess a low-affinity isomer(s) of CK with similar maximum enzymatic activity, there is a high affinity isomer present within the urinary bladder muscle of diabetic rats that is not present in bladder tissue isolated from control rats. Skeletal muscle isolated from both diabetic and control rats exhibited a maximal activity 2 to 3 times higher than that of the bladder.
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PMID:Creatine kinase activity of urinary bladder and skeletal muscle from control and streptozotocin-diabetic rats. 214 63

Autonomic neuropathy and urinary bladder function were compared in Sprague-Dawley rats with alloxan-diabetes of 3 months duration, rats fed sucrose for 8 weeks, and rats examined 8 weeks after pelvic nerve surgical axotomy; normal age-matched rats were used as controls. All experimental interventions induced bladder hypertrophy with increased bladder weight. In diabetic and sucrose-fed animals, water intake and urinary output increased. Cystometric recordings of normal rats in vivo showed rhythmic contractions (1.25 +/- 0.25 contr/min) with threshold volume for micturition reflex at 0.51 +/- 0.04 ml. In diabetic rats, bladder contractions were irregular and of lower frequency (0.60 +/- 0.04 contr/min), while threshold volume was significantly higher (1.00 +/- 0.11 ml). Bladder contractions were normal in sucrose-fed animals, though threshold volume was markedly augmented (1.27 +/- 0.19 ml). Pelvic nerve surgical ablation abolished micturition reflex. In bladder strips excised post-mortem, contractile response to field stimulation was reduced in diabetic rats compared to control and sucrose-fed animals. Morphological examination of pelvic and hypogastric nerves revealed abnormalities characteristic of diabetic neuropathy only in diabetic rats. These data suggest that in alloxan-induced diabetes the decrease in the rate of bladder contraction is the result of autonomic neuropathy; while bladder hypertrophy in sucrose-fed rats appears to be an organ adaptation to hyperdiuresis.
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PMID:Cystometric changes in alloxan diabetic rats: evidence for functional and structural correlates of diabetic autonomic neuropathy. 234 50

The question still remains: What is best for the patient? It appears that whole organ or segmental pancreas transplantation can be carried out, giving anywhere from a 46% to an 84% 1-year pancreas survival rate. At the moment there is no clear-cut evidence that patient survival--at least in the short term--is any better after a combined pancreas-kidney graft than after a kidney graft alone, and there are more complications from the combined procedure. It appears once again that patient survival is a function of control of ketoacidosis and its complications--whether by a pancreas graft or by better insulin delivery. Nevertheless, several things have been learned: (1) Patients who receive a pancreas-kidney graft simultaneously have the best pancreas 1-year survival. (2) A pancreatic graft without a simultaneous kidney graft does poorly. (3) A pancreas graft carried out after a kidney graft will not do as well. (4) A kidney transplanted to a diabetic patient may become nephropathic unless supported by a pancreatic graft. (5) Retinopathy is not improved by pancreatic transplantation. (6) Neuropathy is improved or stabilized by pancreatic transplantation. (7) Nephropathy is improved by pancreatic grafting. (8) There is no clear-cut difference in pancreatic graft survival, whether segmental or whole organ grafts are used. (9) Bladder-drained grafts appear to have slightly better survival at 1 year than enteric-drained or polymer-injected grafts. (10) Human islet cell homotransplantation is not yet an accomplished fact. As Barker has pointed out, the potential benefits of pancreatic grafting are for those who are prone to complications and who do not have irreversible diabetic complications. Predicting those in whom significant complications will develop is not easy, and a large percentage of the grafts done to date have been done for patients with end stage renal disease. It has been suggested that transplants are best used for those with early renal disease and for those with pre-proliferative retinopathy and for those that are metabolically difficult to handle with insulin and for those at high risk for complications with diabetes: namely, those with high levels of inactive renin that are associated with microvascular complications and high levels of insulin-like growth factor. These complications seem to be associated with accelerated progression of retinopathy. Diabetic children whose disease is associated with major neurovascular disease and children with impaired counter regulatory mechanisms may also be candidates for grafting.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Where are we with pancreas transplantation? 268 60

Bladder dysfunction is a common complication of diabetes mellitus and is attributed in part to peripheral neuropathy. We investigated the effects of experimental diabetes on muscarinic receptors in rat bladder smooth muscle, 2, 4 and 8 weeks after i.v. injection of 65 mg/kg of streptozotocin. At all time points, diabetic animals had a lower body weight, higher serum glucose levels and reduced serum insulin levels than age-matched controls. Diabetic animals had a markedly increased urine output and significant enlargement of the bladder dome. The amount of muscarinic receptor labeled with [3H]quinuclidinyl benzylate (QNB) was higher in the bladder dome of diabetic animals than control animals, whereas the affinity of the labeled antagonist for its binding sites was similar in both groups. Muscarinic agonists and antagonists inhibited [3H]QNB binding with similar inhibitory constants (Ki) in control and diabetic dome. The rank order of Ki values in inhibition of [3H]QNB binding by muscarinic agonists and antagonists: atropine less than acetylcholine less than carbachol less than AF-DX 116 = pirenzepine less than bethanechol, is consistent with the presence of M2 muscarinic receptors in the bladder dome. In functional studies, muscarinic agonists induced a larger contractile response in bladder dome muscle strips from 8-week-diabetic animals than from controls. ED50 values were similar in control and treated groups, with the rank order of ED50 values being in good agreement with the Ki values obtained from receptor binding studies, i.e., acetylcholine less than carbachol less than bethanechol. These data show a direct correlation between the diabetes-induced biochemical and functional alterations in muscarinic receptor properties of rat bladder.
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PMID:Effects of experimental diabetes on biochemical and functional characteristics of bladder muscarinic receptors. 291 90

The effects of the aldose reductase inhibitor (ARI) sorbinil (250 mg/day) were tested in an open-label pilot study over 1 year, in eight diabetics with peripheral neuropathy, seven of whom had symptomic autonomic neuropathy (AN). Autonomic function studies of the urinary bladder, stomach and cardiovascular system were performed at baseline, 6 and 12 months. Six patients reported improvement in symptoms of AN by 6 months which was maintained or further improved by 12 months. Bladder sensation, as measured by cystometrographic parameters, improved at 6 months (P less than 0.02- less than 0.04), but by 12 months had reverted to baseline. Residual urine volume decreased at 6 months (P less than 0.06) and 12 months (P less than 0.06). Vagally mediated gastric acid secretion improved at 6 months (P less than 0.06); the subgroup of patients with subnormal secretion showed improvement to the normal range at 6 months (P less than 0.03). Gastric emptying of solid food was normal in six of eight subjects and showed no significant change at 6 months. Both patients with delayed emptying normalized. No change in beat-to-beat variability in heart rate with respiration was noted. Resting minimum heart rate decreased at 12 months (P less than 0.05). Glycohemoglobin levels showed no statistically significant changes. No toxic reactions were observed. These data suggest a beneficial effect of ARI treatment on symptomatic and asymptomatic manifestations of diabetic autonomic neuropathy and indicate a need for large controlled trials.
Diabetes Res Clin Pract 1987 Nov
PMID:Influence of long-term aldose reductase inhibitor therapy on autonomic dysfunction of urinary bladder, stomach and cardiovascular systems in diabetic patients. 312 Dec 73

Bladder disorders are important among the various complications of diabetes, both because of their frequency and the severe involvements they can cause to the urinary tract and ultimately to the renal function. Because they are often mild, especially in the first stage, bladder disorders call for early detection and for a judicious assessment as possible by careful investigation. The incidence of bladder disorders was studied in 50 diabetics by performing cystoscopy, micturition cystourethrography and cystometry. The results emphasize the importance of these investigations, particularly the cystometric one, in recognizing such bladder troubles before severe complications occur.
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PMID:Incidence and diagnostic aspects of the bladder disorders in diabetics. 722

Studies were done to compare the acute effects of streptozotocin-induced diabetes and sucrose consumption on micturition, bladder mass and contractile responses of bladder strips to field stimulation and contractile agonists. Micturition changes occurred gradually in diabetic rats, reached maximal values within 7 to 14 days, and were accompanied by significant increases in bladder mass after 7 days. Bladder strips from diabetics responded to field stimulation, carbachol and KCl with significantly greater contractions than did those from controls within 7 days. Sucrose-drinking rats had maximal increases in fluid consumption and micturition frequency on the first night after starting treatment. Increases in micturition volumes were slower to develop than in diabetics. Bladder mass was significantly increased 30 and 60 days after starting sucrose treatment. Bladder strips from sucrose-drinking rats responded to field stimulation and carbachol with significantly greater contractions than did those from controls only after 60 days. Monitoring of drinking and micturition patterns established that diabetic rats drink and urinate during both the dark and light cycles. In contrast, control and sucrose-drinking rats drink and urinate principally at night. The results demonstrate that differences in bladder function between diabetic and sucrose drinking rats are apparent during the first month after treatment begins. The data suggest that the effects of diabetes and sucrose consumption on contractile bladder function are related to the diuresis-induced increases in bladder mass.
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PMID:Temporal changes in micturition and bladder contractility after sucrose diuresis and streptozotocin-induced diabetes mellitus in rats. 775 86


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