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Sioux Falls, SD, United States

Skarbaliene J.,Research and Development | Secher T.,Gubra ApS | Jelsing J.,Gubra ApS | Ansarullah,Children Health Research Center | And 5 more authors.
Peptides | Year: 2015

Aims/hypothesis Combination treatment with exendin-4 and gastrin has proven beneficial in treatment of diabetes and preservation of beta cell mass in diabetic mice. Here, we examined the chronic effects of a GLP-1-gastrin dual agonist ZP3022 on glycemic control and beta cell dysfunction in overtly diabetic Zucker Diabetic Fatty (ZDF) rats. Methods ZDF rats aged 11 weeks were dosed s.c., b.i.d. for 8 weeks with vehicle, ZP3022, liraglutide, exendin-4, or gastrin-17 with or without exendin-4. Glycemic control was assessed by measurements of HbA1c and blood glucose levels, as well as glucose tolerance during an oral glucose tolerance test (OGTT). Beta cell dynamics were examined by morphometric analyses of beta and alpha cell fractions. Results ZP3022 improved glycemic control as measured by terminal HbA1c levels (6.2 ± 0.12 (high dose) vs. 7.9 ± 0.07% (vehicle), P < 0.001), as did all treatments, except gastrin-17 monotherapy. In contrast, only ZP3022, exendin-4 and combination treatment with exendin-4 and gastrin-17 significantly improved glucose tolerance and increased insulin levels during an OGTT. Moreover, only ZP3022 significantly enhanced the beta cell fraction in ZDF rats, a difference of 41%, when compared to the vehicle group (0.31 ± 0.03 vs. 0.22 ± 0.02%, respectively, P < 0.05). Conclusion These data suggest that ZP3022 may have therapeutic potential in the prevention/delay of beta cell dysfunction in type 2 diabetes. © 2015 Elsevier Inc.All rights reserved. Source


Khan S.,University of Tennessee Health Science Center | Ansarullah,Children Health Research Center | Kumar D.,University of the District of Columbia | Jaggi M.,University of Tennessee Health Science Center | Chauhan S.C.,University of Tennessee Health Science Center
Cancer Research | Year: 2013

The prognosis of patients with pancreatic cancer is extremely poor, and current systemic therapies result in only marginal survival rates for patients. The era of targeted therapies has offered a new avenue to search for more effective therapeutic strategies. Recently, microRNAs (miRNA) that are small noncoding RNAs (18-24 nucleotides) have been associated with a number of diseases, including cancer. Disruption of miRNAs may have important implications in cancer etiology, diagnosis, and treatment. So far, focus has been on the mechanisms that are involved in translational silencing of their targets to fine tune gene expression. This review summarizes the approach for rational validation of selected candidates that might be involved in pancreatic tumorigenesis, cancer progression, and disease management. Herein, we also focus on the major issues hindering the identification of miRNAs, their linked pathways and recent advances in understanding their role as diagnostic/ prognostic biomarkers, and therapeutic tools in dealing with this disease. miRNAs are expected to be robust clinical analytes, valuable for clinical research and biomarker discovery. ©2013 AACR. Source


Barzegar M.,Children Health Research Center | Rouhi A.H.J.,Fellow of Pediatric Pulmonology | Farhoudi M.,Tabriz University of Medical Sciences | Sardashti S.,Children Health Research Center
Annals of Indian Academy of Neurology | Year: 2012

Although it is a sporadic disease, few studies have reported cases of Guillain Barre Syndrome (GBS) in families which postulate a genetic susceptibility. Human leukocyte antigen (HLA) typing is an area of discussion in GBS though none of them are considered definitive. In recent years, more studies have evaluated HLA typing in sporadic cases while rarely it has been assessed in familial ones. We report a woman and her daughter experiencing GBS and their HLA typing in a 2-year interval. Source


Ansarullah,Children Health Research Center | Free C.,Children Health Research Center | Christopherson J.,Children Health Research Center | Chen Q.,Children Health Research Center | And 7 more authors.
Journal of Diabetes Research | Year: 2016

Using humanized mice with functional human islets, we investigated whether activating GPR119 by PSN632408, a small molecular agonist, can stimulate human β-cell regeneration in vivo. Human islets were transplanted under the left kidney capsule of immunodeficient mice with streptozotocin- (STZ-) induced diabetes. The recipient mice were treated with PSN632408 or vehicle and BrdU daily. Human islet graft function in the mice was evaluated by nonfasting glucose levels, oral glucose tolerance, and removal of the grafts. Immunostaining for insulin, glucagon, and BrdU or Ki67 was performed in islet grafts to evaluate and β-cell replication. Insulin and CK19 immunostaining was performed to evaluate β-cell neogenesis. Four weeks after human islet transplantation, 71% of PSN632408-treated mice achieved normoglycaemia compared with 24% of vehicle-treated mice. Also, oral glucose tolerance was significantly improved in the PSN632408-treated mice. PSN632408 treatment significantly increased both human and β-cell areas in islet grafts and stimulated and β-cell replication. In addition, β-cell neogenesis was induced from pancreatic duct cells in the islet grafts. Our results demonstrated that activation of GPR119 increases β-cell mass by stimulating human β-cell replication and neogenesis. Therefore, GPR119 activators may qualify as therapeutic agents to increase human β-cell mass in patients with diabetes. © 2016 Ansarullah et al. Source


Ansarullah,Children Health Research Center | Lu Y.,Children Health Research Center | Holstein M.,Children Health Research Center | DeRuyter B.,Children Health Research Center | And 4 more authors.
PLoS ONE | Year: 2013

Background: Activating G-protein coupled receptor 119 (GPR119) by its agonists can stimulate glucagon like peptide-1 (GLP-1) release. GLP-1 is rapidly degraded and inactivated by dipeptidylpeptidase-IV (DPP-IV). We studied the efficiency of combining PSN632408, a GPR119 agonist, with sitagliptin, a DPP-IV inhibitor, on β-cell regeneration in diabetic mice. Materials & Methods: Diabetes in C57BL/6 mice was induced by streptozotocin. PSN632408 and sitagliptin alone or in combination were administered to diabetic mice for 7 weeks along with BrdU daily. Nonfasting blood glucose levels were monitored. After treatment, oral glucose tolerance test (OGTT), plasma active GLP-1 levels, β-cell mass along with α- and β-cell replication, and β-cell neogenesis were evaluated. Results: Normoglycemia was not achieved in vehicle-treated mice. By contrast, 32% (6 of 19) of PSN632408-treated diabetic mice, 36% (5 of 14) sitagliptin-treated diabetic mice, and 59% (13 of 22) diabetic mice treated with PSN632408 and sitagliptin combination achieved normoglycemia after 7 weeks treatment. Combination therapy significantly increased plasma active GLP-1 levels, improved glucose clearance, stimulated both α- and β-cell replication, and augmented β-cell mass. Furthermore, treatment with combination therapy induced β-cell neogenesis from pancreatic duct-derived cells. Conclusion: Our results demonstrate that combining a GPR119 agonist with a DPP-IV inhibitor may offer a novel therapeutic strategy for stimulating β-cell regeneration and reversing diabetes. © 2013 Ansarullah et al. Source

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