BACKGROUND Diabetes mellitus(DM)is a serious and growing global health burden.It is estimated that 80%of diabetic patients have micturition problems such as poor emptying,urinary incontinence,urgency,and urgency incon...BACKGROUND Diabetes mellitus(DM)is a serious and growing global health burden.It is estimated that 80%of diabetic patients have micturition problems such as poor emptying,urinary incontinence,urgency,and urgency incontinence.Patients with diabetic bladder dysfunction are often resistant to currently available therapies.It is necessary to develop new and effective treatment methods.AIM To examine the therapeutic effect of human amniotic fluid stem cells(hAFSCs)therapy on bladder dysfunction in a type 2 diabetic rat model.METHODS Sixty female Sprague-Dawley rats were divided into five groups:Group 1,normal-diet control(control);group 2,high-fat diet(HFD);group 3,HFD plus streptozotocin-induced DM(DM);group 4,DM plus insulin treatment(DM+insulin);group 5,DM plus hAFSCs injection via tail vein(DM+hAFSCs).Conscious cystometric studies were done at 4 and 12 wk after insulin or hAFSCs treatment to measure peak voiding pressure,voided volume,intercontraction interval,bladder capacity,and residual volume.Immunoreactivities and/or mRNA expression of muscarinic receptors,nerve growth factor(NGF),and sensory nerve markers in the bladder and insulin,MafA,and pancreatic-duodenal homeobox-1(PDX-1)in pancreatic beta cells were studied.RESULTS Compared with DM rats,insulin but not hAFSCs treatment could reduce the bladder weight and improve the voided volume,intercontraction interval,bladder capacity,and residual volume(P<0.05).However,both insulin and hAFSCs treatment could help to regain the blood glucose and bladder functions to the levels near controls(P>0.05).The immunoreactivities and mRNA expression of M2-and M3-muscarinic receptors(M2 and M3)were increased mainly at 4 wk(P<0.05),while the number of beta cells in islets and the immunoreactivities and/or mRNA of NGF,calcitonin gene-related peptide(CGRP),substance P,insulin,MafA,and PDX-1 were decreased in DM rats(P<0.05).However,insulin and hAFSCs treatment could help to regain the expression of M2,M3,NGF,CGRP,substance P,MafA,and PDX-1 to near the levels of controls at 4 and/or 12 wk(P>0.05).CONCLUSION Insulin but not hAFSCs therapy can recover the bladder dysfunction caused by DM;however,hAFSCs and insulin therapy can help to regain bladder function to near the levels of control.展开更多
Objective To review studies on diabetic bladder dysfunction （DBD）,a common and bothersome complication of diabetes mellitus.Data sources We performed a search of the English literature through PubMed.The key words u...Objective To review studies on diabetic bladder dysfunction （DBD）,a common and bothersome complication of diabetes mellitus.Data sources We performed a search of the English literature through PubMed.The key words used were ＂diabetes＂ and ＂bladder dysfunction＂ or ＂cystopathy＂.Our own data and perspective are included in the discussion.Study selection Studies containing data relevant to DBD were selected.Because of the limited length of this article,we also referenced reviews that contain comprehensive amalgamations of relevant literature.Results The classic symptoms of DBD are decreased bladder sensation,increased bladder capacity,and impaired bladder emptying with resultant elevated post-void residual urine.However,recent clinical and experimental evidence indicate a strong presence of storage problems such as urge incontinence in diabetes.Recent studies of DBD in animal models of type 1 diabetes have revealed temporal effects of diabetes,causing an early phase of compensatory bladder function and a later phase of decompensated bladder function.The pathophysiology of DBD is multifactorial,including disturbances of the detrusor,urothelium,autonomic nerves,and urethra.Polyuria and hyperglycemia play important but distinctive roles in induction of bladder dysfunction in type 1 diabetes.Polyuria causes significant bladder hypertrophy in the early stage of diabetes,whereas oxidative stress in the bladder caused by chronic hyperglycemia may play an important role in the late stage failure of bladder function.Conclusions DBD includes time-dependent and mixed manifestations.The pathological alterations include muscle,nerve,and urothelium.Polyuria and hyperglycemia independently contribute to the pathogenesis of DBD.Treatments for DBD are limited.Future clinical studies on DBD in type 1 and type 2 diabetes should be investigated separately.Animal studies of DBD in type 2 diabetes are needed,from the natural history to mechanisms.Further understanding of the molecular mechanisms of DBD will provide multiple potential targets for therapeutic intervention.展开更多
基金Supported by the Linkou Chang Gung Memorial Hospital grants,No. CMRPG3J0951 and No. CMRPG3H1041-2Ministry of Science and Technology Taiwan grants,No. MOST 107-2314-B-182A-101 and No. MOST 109-2314-B-182A-084
文摘BACKGROUND Diabetes mellitus(DM)is a serious and growing global health burden.It is estimated that 80%of diabetic patients have micturition problems such as poor emptying,urinary incontinence,urgency,and urgency incontinence.Patients with diabetic bladder dysfunction are often resistant to currently available therapies.It is necessary to develop new and effective treatment methods.AIM To examine the therapeutic effect of human amniotic fluid stem cells(hAFSCs)therapy on bladder dysfunction in a type 2 diabetic rat model.METHODS Sixty female Sprague-Dawley rats were divided into five groups:Group 1,normal-diet control(control);group 2,high-fat diet(HFD);group 3,HFD plus streptozotocin-induced DM(DM);group 4,DM plus insulin treatment(DM+insulin);group 5,DM plus hAFSCs injection via tail vein(DM+hAFSCs).Conscious cystometric studies were done at 4 and 12 wk after insulin or hAFSCs treatment to measure peak voiding pressure,voided volume,intercontraction interval,bladder capacity,and residual volume.Immunoreactivities and/or mRNA expression of muscarinic receptors,nerve growth factor(NGF),and sensory nerve markers in the bladder and insulin,MafA,and pancreatic-duodenal homeobox-1(PDX-1)in pancreatic beta cells were studied.RESULTS Compared with DM rats,insulin but not hAFSCs treatment could reduce the bladder weight and improve the voided volume,intercontraction interval,bladder capacity,and residual volume(P<0.05).However,both insulin and hAFSCs treatment could help to regain the blood glucose and bladder functions to the levels near controls(P>0.05).The immunoreactivities and mRNA expression of M2-and M3-muscarinic receptors(M2 and M3)were increased mainly at 4 wk(P<0.05),while the number of beta cells in islets and the immunoreactivities and/or mRNA of NGF,calcitonin gene-related peptide(CGRP),substance P,insulin,MafA,and PDX-1 were decreased in DM rats(P<0.05).However,insulin and hAFSCs treatment could help to regain the expression of M2,M3,NGF,CGRP,substance P,MafA,and PDX-1 to near the levels of controls at 4 and/or 12 wk(P>0.05).CONCLUSION Insulin but not hAFSCs therapy can recover the bladder dysfunction caused by DM;however,hAFSCs and insulin therapy can help to regain bladder function to near the levels of control.
文摘Objective To review studies on diabetic bladder dysfunction （DBD）,a common and bothersome complication of diabetes mellitus.Data sources We performed a search of the English literature through PubMed.The key words used were ＂diabetes＂ and ＂bladder dysfunction＂ or ＂cystopathy＂.Our own data and perspective are included in the discussion.Study selection Studies containing data relevant to DBD were selected.Because of the limited length of this article,we also referenced reviews that contain comprehensive amalgamations of relevant literature.Results The classic symptoms of DBD are decreased bladder sensation,increased bladder capacity,and impaired bladder emptying with resultant elevated post-void residual urine.However,recent clinical and experimental evidence indicate a strong presence of storage problems such as urge incontinence in diabetes.Recent studies of DBD in animal models of type 1 diabetes have revealed temporal effects of diabetes,causing an early phase of compensatory bladder function and a later phase of decompensated bladder function.The pathophysiology of DBD is multifactorial,including disturbances of the detrusor,urothelium,autonomic nerves,and urethra.Polyuria and hyperglycemia play important but distinctive roles in induction of bladder dysfunction in type 1 diabetes.Polyuria causes significant bladder hypertrophy in the early stage of diabetes,whereas oxidative stress in the bladder caused by chronic hyperglycemia may play an important role in the late stage failure of bladder function.Conclusions DBD includes time-dependent and mixed manifestations.The pathological alterations include muscle,nerve,and urothelium.Polyuria and hyperglycemia independently contribute to the pathogenesis of DBD.Treatments for DBD are limited.Future clinical studies on DBD in type 1 and type 2 diabetes should be investigated separately.Animal studies of DBD in type 2 diabetes are needed,from the natural history to mechanisms.Further understanding of the molecular mechanisms of DBD will provide multiple potential targets for therapeutic intervention.
