Diabetes mellitus (DM) is a serious and growing global health burden. Of individuals diagnosed with DM, 80% have storage and emptying urination problems. There are many therapeutic options for voiding symptoms in patients with diabetic bladder dysfunction; however, these patients are often resistant to currently available therapies. The aim of study was to examine the effects of human amniotic fluid stem cells (hAFSCs) transplantation and insulin therapy on ameliorating bladder dysfunction in type 2 diabetic rats.

Sixty female Sprague-Dawley rats were divided into 5 groups: normal control, high fat diet fed rats (HFD), HFD and streptozotocin (STZ, 30 mg/kg)-induced diabetic rats (DM), DM plus insulin treatment (DM+Insulin), and hAFSCs transplantation (DM+hAFSCs). Cystometries, the expressions of bladder muscarinic receptors, nerve growth factor (NGF) and sensory nerve markers, and the expressions of insulin, MafA and pancreas-duodenum homeobox-1(PDX-1) in pancreatic beta cells were studied at 4 and 12 weeks after DM induction.

Insulin treatment can reduce the bladder weight and blood sugar level in DM rats, but hHAFSCs transplantation cannot. The voided volume, inter-contraction interval, bladder capacity and residual volume of DM rats increased significantly, and improved after insulin and hAFSCs treatment. Compared with the control group, the immunoreactivity and mRNA expression of M2 and M3 of DM rats were increased, but NGF, calcitonin gene-related peptide (CGRP) and substance P were decreased. Both insulin and hAFSCs treatment improved the expressions of M2, M3, NGF, CGRP and substance P at 4 weeks after DM induction. Number of beta cells in islets and immunoreactivities of insulin, MafA and PDX-1 decreased in DM rats. Insulin and hAFSCs treatment can increase the expressions of insulin, MafA and PDX-1 at 4 weeks and/or 8 weeks after DM induction.

Our results indicate that bladder weight and blood glucose increased in STZ-induced diabetic rats, but returned to normal after exogenous insulin treatment. HAFSCs transplantation cannot restore bladder weight and blood glucose in STZ-induced diabetic rats, so the role of hAFSCs in improving diabetes bladder dysfunction is different from that of insulin in regulating blood glucose levels. In this study, we explain our findings and summarize them as follows: 1. Bladder dysfunctions subsequent to DM induction were improved after insulin treatment and hAFSCs transplantation; 2. Expressions of M2, M3, NGF, CGRP and Substance P were improved after insulin treatment and hAFSCs transplantation; 3. Insulin and hAFSCs treatment can increase insulin, MafA and PDX-1 expression.

Similar to insulin therapy, hAFSCs transplantation can improve bladder dysfunction in STZ-induced DM rats, partly associated with the expression of NGF, muscarinic receptors and sensory nerve markers, and partly related to hAFSCs protecting the biochemical and microscopic changes in pancreatic beta cells.

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