Research advances in total pancreatectomy with autologous islet cell transplantation / 临床肝胆病杂志

Since the 1970s， patients with chronic pancreatitis （CP） have benefited from total pancreatectomy with autologous islet cell transplantation （TPAIT）. With the continuous development of surgical techniques and perioperative management over the past few decades， there have been improvements in islet cell function， insulin independence rate， and the survival rate of patients. This article summarizes the preoperative indications for TPAIT， the development of surgical operations， postoperative management and monitoring， and prognosis， so as to help clinicians learn more about TPAIT.

Current status and future of new technologies in the treatment of type 1 diabetes / 中国医师杂志

Type 1 diabetes mellitus (T1DM) is an organ-specific disease characterized by autoimmune damage to pancreatic β cells. Insulin therapy is the most basic and important treatment for T1DM, but insulin therapy cannot fundamentally terminate or improve the main cause of T1DM, namely the disorder of the immune regulation mechanism. With the advancement of science and technology, the continuous development of new insulin and hypoglycemic drugs has provided better means for glycemic control. Pancreas transplantation, islet transplantation, immunotherapy, and cell therapy have provided hope for the prevention or reversal of T1DM. It is of great significance to understand the current situation and future of new technologies for T1DM treatment for the research and management of T1DM patients.

The research progress of total pancreatectomy with islet autotransplantation for chronic pancreatitis patients / 中华肝胆外科杂志

Chronic pancreatitis is a progressive chronic inflammatory disease of caused by gene and other environmental factors, and clinical manifestation includes recurrent abdominal pain and dysfunction of exocrine and endocrine. For the chronic pancreatitis therapy, surgical treatment mainly aims at the intractable pain which is unresponsive to medical and endoscopic treatment, as well as complications of chronic pancreatitis. Total pancreatectomy with islet autotransplantation (TPIAT) gradually becomes a major therapeutic option for chronic pancreatitis surgical treatment, because it relieves the abdominal pain, reduces the opioid dependent, improves the quality of life, and increases the opportunity of insulin independent. In the past few years, a range of researches have been focusing on islet isolation, surgical approach, curative effect and postoperative complication, improvement of islet function after operation. The purpose of this article is to summarize the progression of TPIAT related research in the recent years.

A Novel Pancreatic Imaging Window for Stabilized Longitudinal In Vivo Observation of Pancreatic Islets in Murine Model

Longitudinal imaging of murine pancreas is technically challenging due to the mechanical softness of the tissue influenced by peristalsis. Here, we report a novel pancreatic imaging window for long-term stabilized cellular-level observation of the islets in the pancreas in vivo. By spatially separating the pancreas from the bowel movement and physiologic respiration with a metal plate integrated in the imaging window, we successfully tracked the pancreatic islets up to three weeks and visualized the dumbbell-shape transformation from the single islet. This window can be a useful tool for long-term cellular-level visualization of the microstructure in the pancreas.

Chronic treatment with hydroalcoholic extract of Plathymenia reticulata promotes islet hyperplasia and improves glycemic control in diabetic rats / Tratamento crônico com extrato hidroalcoólico de Plathymenia reticulata promove hiperplasia de ilhotas e controle glicêmico em ratos diabéticos

ABSTRACT Objective: To investigate the anti-hyperglycemic effects of Plathymenia reticulata hydroalcoholic extract and related changes in body weight, lipid profile and the pancreas. Methods: Diabetes was induced in 75 adult male Wistar rats via oral gavage of 65mg/Kg of streptozotocin. Rats were allocated to one of 8 groups, as follows: diabetic and control rats treated with water, diabetic and control rats treated with 100mg/kg or 200mg/kg of plant extract, and diabetic and control rats treated with glyburide. Treatment consisted of oral gavage for 30 days. Blood glucose levels and body weight were measured weekly. Animals were sacrificed and lipid profile and pancreatic tissue samples analyzed. Statistical analysis consisted of ANOVA, post-hoc Tukey-Kramer, paired Student's t and χ2 tests; the level of significance was set at 5%. Results: Extract gavage at 100mg/kg led to a decrease in blood glucose levels in diabetic rats in the second, third (198.71±65.27 versus 428.00±15.25) and fourth weeks (253.29±47.37 versus 443.22±42.72), body weight loss (13.22±5.70 versus 109.60±9.95) and lower cholesterol levels (58.75±3.13 versus 80.11±4.01) in control rats. Extract gavage at 200mg/Kg led to a decrease in glucose levels on the fourth week in diabetic rats, body weight loss in the second, third and fourth weeks in control rats, and lower cholesterol levels in diabetic and control rats. Islet hyperplasia (p=0.005) and pancreatic duct dilation (p=0.047) were observed in diabetic and control rats. Conclusion: Plathymenia extract reduced blood glucose levels in diabetic rats, and body weight in control rats, and promoted pancreatic islet hyperplasia in diabetic and control rats.

RESUMO Objetivo: Avaliar o efeito anti-hiperglicêmico do extrato hidroalcoólico de Plathymenia reticulata, alterações no peso, lipídeos e efeito sobre o pâncreas. Métodos: O diabetes foi induzido pela administração de estreptozotocina 65mg/kg, em 75 ratos Wistar adultos machos, divididos em 8 grupos diferentes: ratos diabéticos e controle + água, ratos diabéticos e controle + 100mg/kg ou 200mg/kg de extrato, ratos diabéticos e controle + gliburida. O tratamento foi realizado por gavagem (oral) por 30 dias. Níveis de glicose e peso foram verificados semanalmente. Os animais foram sacrificados, e amostras de lipídeos e do pâncreas foram analisadas. A análise estatística incluiu ANOVA, post-hoc Tukey-Kramer, teste t de Student pareado e teste do χ2, com nível de significância de 5%. Resultados: O extrato 100mg/kg promoveu redução nos níveis de glicose sanguínea em ratos diabéticos na segunda, terceira (198,71±65,27 versus 428,00±15,25) e quarta semanas (253,29±47,37 versus 443,22±42,72), perda de peso (13,22±5,70 versus 109,60±9,95) e diminuição do colesterol (58,75±3,13 versus 80,11±4,01) em ratos controle. Com extrato de 200mg/kg, houve redução dos níveis de glicose na quarta semana, nos ratos diabéticos; de peso na segunda, terceira e quarta semanas, nos ratos controle; e de colesterol nos animais diabéticos e controle. Ocorreram hiperplasia de ilhotas (p=0,005) e dilatação dos ductos pancreáticos (p=0,047) em ratos diabéticos e controles. Conclusão: O extrato de Plathymenia reduziu os níveis de glicose em ratos diabéticos e de peso em ratos controle, além de ter promovido hiperplasia de ilhotas pancreáticas em diabéticos e controles.

Reduction of Inflammation and Enhancement of Motility after Pancreatic Islet Derived Stem Cell Transplantation Following Spinal Cord Injury

OBJECTIVE: Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI.METHODS: rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, S100β, brain derived neurotrophic factor (BDNF), 2’,3’-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor [TGF]-β, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors.RESULTS: rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), β3-tubulin and nestin as well as antiinflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined.CONCLUSION: Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

Reduction of Inflammation and Enhancement of Motility after Pancreatic Islet Derived Stem Cell Transplantation Following Spinal Cord Injury

OBJECTIVE: Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI. METHODS: rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, S100β, brain derived neurotrophic factor (BDNF), 2’,3’-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor [TGF]-β, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors. RESULTS: rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), β3-tubulin and nestin as well as antiinflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined. CONCLUSION: Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

Essential Role of Protein Arginine Methyltransferase 1 in Pancreas Development by Regulating Protein Stability of Neurogenin 3

BACKGROUND: Protein arginine methyltransferase 1 (PRMT1) is a major enzyme responsible for the formation of methylarginine in mammalian cells. Recent studies have revealed that PRMT1 plays important roles in the development of various tissues. However, its role in pancreas development has not yet been elucidated. METHODS: Pancreatic progenitor cell-specific Prmt1 knock-out (Prmt1 PKO) mice were generated and characterized for their metabolic and histological phenotypes and their levels of Neurog3 gene expression and neurogenin 3 (NGN3) protein expression. Protein degradation assays were performed in mPAC cells. RESULTS: Prmt1 PKO mice showed growth retardation and a severely diabetic phenotype. The pancreatic size and β-cell mass were significantly reduced in Prmt1 PKO mice. Proliferation of progenitor cells during the secondary transition was decreased and endocrine cell differentiation was impaired. These defects in pancreas development could be attributed to the sustained expression of NGN3 in progenitor cells. Protein degradation assays in mPAC cells revealed that PRMT1 was required for the rapid degradation of NGN3. CONCLUSION: PRMT1 critically contributes to pancreas development by destabilizing the NGN3 protein.

Alginate-Catechol Cross-Linking Interferes with Insulin Secretion Capacity in Isolated Murine Islet Cells

Over the past three decades, human pancreatic islet isolation and transplantation techniques have developed as a routine clinical procedure for selected patients with type 1 diabetes mellitus. However, due to the donor shortage and required chronic systemic immunosuppression, the widespread application of islet transplantation is limited. To overcome these limitations, providing a physical barrier to transplanted islet cells with encapsulating biomaterial has emerged as a promising approach to enhance engraftment and promote islet survival post-transplantation. Alginate has been considered to be a reliable biomaterial, as it enhances islet survival and does not hamper hormone secretion. Alginate-catechol (Al-CA) hydrogel was reported to provide high mechanical strength and chemical stability without deformation over a wide range of pH values. In this study, we, demonstrated, for the first time in the literature, that encapsulation of murine pancreatic islet cells with Al-CA hydrogel does not induce cytotoxicity ex vivo for an extended period; however, it does markedly abate glucose-stimulated insulin secretion. Catechol should not be considered as a constituent for alginate gelation for encapsulating islet cells in the application of islet transplantation.

Human islet xenotransplantation in rodents: A literature review of experimental model trends

Among the innovations for the treatment of type 1 diabetes, islet transplantation is a less invasive method of treatment, although it is still in development. One of the greatest barriers to this technique is the low number of pancreas donors and the low number of pancreases that are available for transplantation. Rodent models have been chosen in most studies of islet rejection and type 1 diabetes prevention to evaluate the quality and function of isolated human islets and to identify alternative solutions to the problem of islet scarcity. The purpose of this study is to conduct a review of islet xenotransplantation experiments from humans to rodents, to organize and analyze the parameters of these experiments, to describe trends in experimental modeling and to assess the viability of this procedure. In this study, we reviewed recently published research regarding islet xenotransplantation from humans to rodents, and we summarized the findings and organized the relevant data. The included studies were recent reports that involved xenotransplantation using human islets in a rodent model. We excluded the studies that related to isotransplantation, autotransplantation and allotransplantation. A total of 34 studies that related to xenotransplantation were selected for review based on their relevance and current data. Advances in the use of different graft sites may overcome autoimmunity and rejection after transplantation, which may solve the problem of the scarcity of islet donors in patients with type 1 diabetes.

Astragalus polysaccharide improves type 2 diabetes mellitus in rats by protecting islet β cells / 第二军医大学学报

Objective To explore the effect of Astragalus polysaccharides (APS) on the function and quantity of islet β cells in rats with type 2 diabetes mellitus (T2DM). Methods SD rats were randomly divided into normal control group, T2DM model group and APS treatment group, with 8 rats in each group. The T2DM rats in the T2DM model group was induced by the combination of high fat diet and streptozotocin, and the rats in the APS treatment group was treated with APS (700 mg·kg-1·d-1, content of APS being 70%). The rats were sacrificed after 8 weeks of drug intervention, and the serum samples were collected to measure fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and fasting insulin (FINS), and to calculate insulin secretion index (HOMA-β value). Pancreas tissues were extracted and stained with Hematoxylin-Eosin to observe the pancreatic histopathological characteristics, and the quantity of islet β cells was observed and calculated with immuno-histochemical method. Results (1) Compared with the normal control group, the rats in T2DM model group had significant increases in the FBG, TG and LDL-C, and significant decreases in the HDL-C, FINS and HOMA-β (P<0.05); compared with the T2DM model group, the rats in APS treatment group had significant decreases in the FBG, TG and LDL-C (P<0.05), and significant increases in the FINS and HOMA-β (P<0.05). (2) Compared with the normal control group, the rats in T2DM model group showed a significant atrophy of the islet accompanied by loss of granular and vacuolar degeneration, and the number of the islet β cells was significantly reduced (P<0.05); compared with the T2DM model group, the rats in APS treatment group showed a significant increase in the islet volume accompanied by improvement of islet degranulation and vacuolar degeneration, and had a significant increase in the number of islet β cells (P<0.05). Conclusion APS can improve the glucose and lipid metabolisms of the T2DM rats, which may be caused by increasing insulin secretion through the protective effect on pancreatic islet β cells.

The relationship between FoxO1 factor and beta cells dedifferentiation / 中国医师杂志

Type 2 diabetes is a chronic metabolic disorder caused by a deficiency of beta cell func-tion leading to varying degrees of insulin deficiency and insulin resistance. The decline of beta cell function is the central part in the development of type 2 diabetes. The dedifferentiation of pancreatic beta cells is one of the important mechanisms of islet dysfunction. In recent years, it has been shown that the decrease of the activity of the transcription factor forkhead box O1 (FoxO1) is closely related to the dedifferentiation of beta cells. The study of the specific mechanism of FoxO1 involved in the dedifferentiation of beta cells and the redifferentiation of the differentiated cells will provide new ideas for the prevention and treatment of type 2 diabetes.

Is islet transplantation a realistic approach to curing diabetes?

Since the report of type 1 diabetes reversal in seven consecutive patients by the Edmonton protocol in 2000, pancreatic islet transplantation has been reappraised based on accumulated clinical evidence. Although initially expected to therapeutically target long-term insulin independence, islet transplantation is now indicated for more specific clinical benefits. With the long-awaited report of the first phase 3 clinical trial in 2016, allogeneic islet transplantation is now transitioning from an experimental to a proven therapy for type 1 diabetes with problematic hypoglycemia. Islet autotransplantation has already been therapeutically proven in chronic pancreatitis with severe abdominal pain refractory to conventional treatments, and it holds promise for preventing diabetes after partial pancreatectomy due to benign pancreatic tumors. Based on current evidence, this review focuses on islet transplantation as a realistic approach to treating diabetes.

Stepwise Approach to Problematic Hypoglycemia in Korea: Educational, Technological, and Transplant Interventions

Impaired awareness of hypoglycemia has been found to be prevalent in 20% to 40% of people with type 1 diabetes. If a similar prevalence exists in Koreans with type 1 diabetes, at a minimum, thousands of people with type 1 diabetes suffer at least one unpredicted episode of severe hypoglycemia per year in Korea. For patients with problematic hypoglycemia, an evidence-based stepwise approach was suggested in 2015. The first step is structured education regarding multiple daily injections of an insulin analog, and the second step is adding a technological intervention, such as continuous subcutaneous insulin infusion or real-time continuous glucose monitoring. The next step is a sensor-augmented pump, preferably with a low glucose suspension feature or very frequent contact, and the final step is islet or pancreas transplantation. In Korea, however, none of these treatments are reimbursed by the National Health Insurance, and thus have not been widely implemented. The low prevalence of type 1 diabetes means that Korean physicians are relatively unfamiliar with the new technologies in this field. Therefore, the roles of new technologies and pancreas or islet transplantation in the treatment of problematic hypoglycemia need to be defined in the current clinical setting of Korea.

Acción de la estreptozotocina en un modelo experimental de inducción neonatal de la diabetes / Streptozotocin diabetogenic action in an experimental neonatal induction model

Introducción. El estudio de la diabetes mediante modelos experimentales es fundamental para entender los mecanismos fisiopatológicos de la enfermedad. Objetivos. Comparar en ratas Wistar adultas la acción de inducción de la diabetes de la estreptozotocina según el momento y la vía de inoculación del fármaco durante el periodo neonatal mediante la evaluación de variables bioquímicas, metabólicas e histológicas. Materiales y métodos. Se conformaron ocho grupos con ratas Wistar hembras recién nacidas (n=10). Se evaluó la inducción con estreptozotocina (100 mg/kg de peso corporal) según el día (segundo y quinto después del nacimiento) y la vía de inoculación (subcutánea o intraperitoneal). Los controles se inyectaron con solución tampón de citrato sódico. Durante 12 semanas se evaluaron la glucemia, el peso, y la cantidad de alimento y de agua consumida. Se hicieron pruebas de tolerancia a la glucosa oral, se evaluó la hemoglobina ´glicosilada´, y se hizo el estudio morfométrico e histopatológico del páncreas. Resultados. Casi todos los animales inoculados con estreptozotocina en el quinto día murieron, en tanto que todos los inoculados en el segundo día sobrevivieron. La administración subcutánea de estreptozotocina en el segundo día produjo hiperglucemia, polifagia, polidipsia y disminución de la ganancia de peso corporal, así como alteración de los valores de hemoglobina ´glicosilada´ y en la prueba de tolerancia a la glucosa. Las lesiones histopatológicas del páncreas, así como la disminución del número de islotes, se observaron con mayor frecuencia con la estreptozotocina aplicada de forma subcutánea en el segundo día, lo cual corroboró que el efecto de este agente inoculado de forma subcutánea causa mayor daño. Conclusiones. La inyección subcutánea de una dosis de 100 mg/kg de estreptozotocina en el segundo día después del nacimiento logró mayor efectividad en la inducción de diabetes moderada en ratas Wistar adultas.

Introduction: The use of experimental models is essential to study the pathophysiological mechanisms of diabetes. Objectives: To compare in adult Wistar rats the diabetogenic action of streptozotocin according to the moment and route of administration during the neonatal period by evaluating biochemical, metabolic and histological variables. Materials and methods: Eight groups of neonatal female Wistar rats (n=10) were formed. We evaluated the induction with streptozotocin (100 mg/kg of body weight) on days 2 and 5 after birth, as well as the administration routes (subcutaneous or intraperitoneal). Controls were injected with sodium citrate buffer. Blood glucose level, body weight, food and water intake were monitored for 12 weeks. We also performed tolerance tests for oral glucose and glycosylated hemoglobin, and a histopathological pancreas morphometric study. Results: The mortality rate was about 100% among rats given streptozotocin on their fifth day of life. All rats receiving the drug on day 2 of life survived, and they showed a marked hyperglycemia, polyphagia, polydipsia and decreased body weight gain in addition to increased glycosylated hemoglobin rates and impaired results in the oral glucose tolerance test. Histopathological lesions of the pancreas as well as a decreased number of islets were significantly more frequent in rats receiving the drug subcutaneously on day 2, which confirms that streptozotocin administered subcutaneously produces greater damage. Conclusions: Subcutaneous injection of streptozotocin in a dose of 100 mg/kg of body weight in the second day after birth induced moderate diabetes in adult Wistar rats more effectively.

Protective effects of kaempferol against fatty acid-induced islet microvessel endothelial function injury and the role of poly(ADP-ribose) polymerases-1 / 第二军医大学学报

Objective To investigate the protective effects of kaempferol against the fatty acid-induced islet microvessel endothelial function injury and the role of poly (ADP-ribose) polymerases-1 (PARP-1). Methods Mouse islet microvessel endothelial MS-1 cells were divided into normal control group, solvent (DMSO) group, fatty acid group (0. 25 mmol/L palmitic acid+0. 5 mmol/L oleic acid), kaempferol group (50 µmol/L), fatty acid + kaempferol group, PARP-1 inhibitor (8 µmol/L BYK204165)+fatty acid group and PARP-1 inhibitors+fatty acidVkaempferol group. The changes of cell viability, apoptosis, nitric oxide (NO), nitric oxide synthase (NOS) and oxidative stress related indicators were examined in each group. Results After treatment with fatty acid, the survival rate of MS-1 cells was significantly decreased and the apoptosis rate was significantly increased (P<0. 05); meanwhile, fatty acids also increased NO production and promoted the activities of the total NOS (tNOS), inducible NOS (iNOS) and constitutive NOS (cNOS) in the MS-1 cells (P<0. 05). Treatment with fatty acid also significantly increased the lipid peroxidation products-malondialdehyde (MDA), while significantly decreased the levels of antioxidants, glutathione (GSH) and superoxide dismutase (SOD) (P<0. 05); and t also increased the mRNA and protein expression of PARP-1, iNOS and cNOS (P <0. 05). Kaempferol significantly attenuated the toxic effects of fatty acidsconcerning all the detected indicators (P<0. 05). Moreover, pretreatment with PARP-1 inhibitor (BYK204165) for 1 h markedly enhanced the protective effects of kaempferol, and all the detected parameters were similar to those of the control group(P<0. 05). Conclusion Fatty acid can directly trigger islet microvessel endothelial function injury, and kaempferol shows a protective effect against the toxicity of fatty acid. Inhibition of PARP-1 can significantly promote the protective effects of kaempferol.

Infusion of mesenchymal stem cells culture supernatant ameliorates hyperglycemia disorders in STZ-induced diabetes mellitus rats / 解放军医学杂志

Objective To evaluate the therapeutic effect of systemic infusion of MSC culture supernatant in STZ-induced diabetic rats, and explore the mechanism of effect of MSC secretion on promoting regeneration of the islet tissues. Methods The diabetic animal model was reproduced in 35 SD rats by intraperitoneal injection of a single large dose of streptozotocin (STZ, 65mg/ kg). The 30 successfully induced diabetic rats were randomly divided into MSC culture supernatant infusion group (CM, n=15) and medium infusion group (M, n=15), and in addition, 15 normal rats were used as control. Animals were intravenously transfused with MSC supernatant (CM group) or raw medium (M group), then the contents of blood glucose were determined 3 days after infusion. The serum insulin and C-peptide levels were monitored and the intraperitoneal glucose tolerance test (IPGTT) was performed on the 7th day of infusion to evaluate the therapeutic effect of MSCs supernatant infusion in diabetic rats. Finally, all the experimental animals were sacrificed at indicated time points and the pancreatic tissues were collected for multiple immunofluorescence staining (MIFS), in order to observe the β-cell regeneration after MSCs supernatant infusion, and to further explore the possible mechanism involved in the experiment. Results At the early stage after infusion (<7 days), the blood glucose level declined and the contents of serum insulin and C-peptide increased obviously in CM group as compared with that of M group (P<0.05). IPGTT showed that the islet function was significantly enhanced in CM group compared with M group. MIFS showed that the number of β cells in the destroyed islets in CM group rats was significantly increased as compared with that of M group rats. In addition, the proliferation rate of β cells was obviously higher in CM group (4%) than in control group (0.5%, P<0.01). Conclusion Treatment with MSCs culture supernatant obviously prompted β cell proliferation in the destroyed islets, resulting in regeneration of the islets with islet function recovery, thus it effectively controls the advance of diabetes.

The effects of Roux-en-Y gastric bypass on expressions of adiponectin and pancreatic islets related apoptotic proteins in type 2 diabetic rats / 天津医药

Objective To explore the anti-apoptotic mechanism of Roux-en-Y gastric bypass (RYGB) through exam?ine the postoperative change of adiponectin levels and expressions of pancreatic islets relative apoptotic protein. Methods Sixty SD rats were randomly allocated to RYGB group (n=20), type 2 diabetes mellitus group (T2DM, n=20) and normal con?trol group (NC, n=20). Rats in the NC group were fed with normal diet. In order to make type 2 diabetic rat models, the rats in the T2DM and RYGB groups were fed with high fat diet (22.19 kJ/g) combined with administration of intraperitoneal strep?tozotocin injection (STZ, 30 mg/kg) on the 13th day of high fat diet. RYGB operation were performed in RYGB group and sham-operation were performed in the T2DM and NC groups when diabetic model was contructed. Rats were weight preoper?atively and at the 7th, 14th, 21st days after operations. Fasting plasma glucose and adiponectin (ELISA) were measured preoper?atively and at 21st day postoperatively. Protein expressions of Bcl-2,Caspase 8 and Caspase 9 in pancreatic islets were ex?amined by immunohistochemistry at the 21st day postoperatively. Results Body weights do not vary significantly among three groups preoperatively. Compared to rats in the NC group, fast plasma glucose level was higher but adiponectin was low?er in rats in RYGB and T2DM groups. Body weights of rats in RYGB group decreased significantly compared to those of rats in NC and T2DM groups postoperatively. Compared to rats in T2DM group, fasting glucose level was lower while adiponectin concentrations was higher in rats in RYGB group but no differences of these parameters were seen in rats in NC group at the 21st day postoperatively. Expression of Bcl-2 in RYGB group was significantly elevated while expressions of Caspase 8 and Caspase 9 were significantly decreased compared to those in T2DM group postoperatively. Conclusion Adiponectin levelswas elevated;expressions of Bcl-2 was increased;expressions of Caspase 8, Caspase 9 were decreased upon RYGB opera?tion in T2DM model. RYGB might reduce pancreatic islets apoptosis through mitochondrial pathway.

Relationship between Acute Pancreatitis and New-onset Diabetes / 胃肠病学

Pancreas is an integrated organ with both endocrine and exocrine functions. Insulin is secreted from the pancreas islet B cell and is the only hormone that could reduce blood sugar and play an important role in glucose homeostasis. Pancreatic disease can result in diabetes mellitus in some cases. Although acute pancreatitis is the most common disease of pancreas,the relationship between acute pancreatitis and new-onset diabetes has been ignored. However,many researches have shown recently that acute pancreatitis is associated with new-onset diabetes. Blood glucose monitoring is warranted for patients after acute pancreatitis with important significance.

Human umbilical cord blood-derived CD133 cells for treatment of gestational diabetes / 中国组织工程研究

BACKGROUND:Human umbilical cord blood contains a large number of hemopoietic stem cels and mesenchymal stem cels. Neonate umbilical cord blood-derived stem cels show milder immunological rejection and lower immunogenicity than peripheral blood- and bone marrow-derived mesenchymal stem cels. OBJECTIVE:To investigate the feasibility of umbilical cord blood-derived CD133 cels for treatment of gestational diabetes, so as to provide novel methods for clinical treatment of gestational diabetes. METHODS:Mouse models of gestational diabetes were established by high-fat and high-sugar diet feeding. Umbilical cord blood-derived CD133 cels were sorted by flow cytometry sorting technique and then transplanted into mouse models of gestational diabetesvia the tail vein. At 7 days after cel transplantation, serum levels of fasting blood glucose, fasting insulin, total cholesterol and triacylglycerol were measured and mouse pancreatic tissue injury and repair was observed by hematoxylin-esoin staining. Mouse insulin resistance index and pancreatic islet function were analyzed using the homeostatic model assessment. RESULTS AND CONCLUSION:Umbilical cord blood-derived CD133 cels could be isolated from umbilical cord blood monocytes using flow cytometry sorting technique, with cel purity of (90.24±2.56)%. At 7 days after cel transplantation, serum levels of fasting blood glucose, fasting insulin, total cholesterol and triacylglycerol were significantly decreased, insulin resistance index was significantly decreased, and pancreatic islet function was significantly improved in mouse models of gestational diabetes (alP < 0.05). In addition, atrophy of pancreatic tissue and infiltration of inflammatory cels were reduced. These results show that umbilical cord blood-derived CD133 cel transplantation can improve the disease condition of gestational diabetes by repairing injured pancreatic tissue, decreasing insulin resistance index and improving pancreatic islet function.