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Islet neogenesis

Hernán Gonzalo Villagarcía, Carolina Lisi Román, María Cecilia Castro, Luisa Arbeláez González, María Teresa Ronco, Daniel Eleazar Francés, María Laura Massa, Bárbara Maiztegui, Luis Emilio Flores, Juan José Gagliardino, Flavio Francini
Islet-Neogenesis Associated Protein-Pentadecapeptide (INGAP-PP) increases β-cell mass and enhances glucose and amino acids-induced insulin secretion. Our aim was to demonstrate its effect on liver metabolism. For that purpose, adult male Wistar rats were injected twice-daily (10 days) with saline solution or INGAP-PP (250 μg). Thereafter, serum glucose, triglyceride and insulin levels were measured and homeostasis model assessment (HOMA-IR) and hepatic insulin sensitivity (HIS) were determined. Liver glucokinase and glucose-6-phosphatase (G-6-Pase) expression and activity, phosphoenolpyruvate carboxykinase (PEPCK) expression, phosphofructokinase-2 (PFK-2) protein content, P-Akt/Akt and glycogen synthase kinase-3β (P-GSK3/GSK3) protein ratios and glycogen deposit were also determined...
January 3, 2018: Peptides
Oskar Skog, Olle Korsgren
The prevailing view is that Type 1 Diabetes (T1D) develops as a consequence of a severe fall in beta-cell mass resulting from T-cell mediated autoimmunity. However, progression from islet autoantibody seroconversion to overt diabetes and finally to total loss of c-peptide production occurs in most affected subjects only slowly over many years or even decades. This slow disease progression should be viewed in relation to the total beta cell mass of only 0.2 - 1.5 g in non-diabetic adults. Focal lesions of acute pancreatitis with accumulation of leukocytes, often located around the ducts, are frequently observed in subjects with recent onset T1D and most patients display extensive periductal fibrosis, the end stage of inflammation...
October 30, 2017: Diabetes, Obesity & Metabolism
Cristina Aguayo-Mazzucato, Susan Bonner-Weir
Diabetes is the result of having inadequate supply of functional insulin-producing β cells. Two possible approaches for replenishing the β cells are: (1) replacement by transplanting cadaveric islets or β cells derived from human embryonic stem cells/induced pluripotent stem cells and (2) induction of endogenous regeneration. This review focuses on endogenous regeneration, which can follow two pathways: enhanced replication of existing β cells and formation of new β cells from cells not expressing insulin, either by conversion from a differentiated cell type (transdifferentiation) or differentiation from progenitors (neogenesis)...
September 5, 2017: Cell Metabolism
Chiyo Shiota, Krishna Prasadan, Ping Guo, Joseph Fusco, Xiangwei Xiao, George K Gittes
AIMS/HYPOTHESIS: The Cre/loxP system, which enables tissue-specific manipulation of genes, is widely used in mice for diabetes research. Our aim was to develop a new Cre-driver mouse line for the specific and efficient manipulation of genes in pancreatic alpha cells. METHODS: A Gcg (CreERT2) knockin mouse, which expresses a tamoxifen-inducible form of Cre from the endogenous preproglucagon (Gcg) gene locus, was generated by homologous recombination. The new Gcg (CreERT2) mouse line was crossed to the Rosa26 (tdTomato) (R26 (tdTomato) ) Cre reporter mouse line in order to evaluate the tissue specificity, efficiency and tamoxifen dependency of Gcg (CreERT2) -mediated recombination...
December 2017: Diabetologia
Hari B Keshava, Ashkan Mowla, Leslie J Heinberg, Philip R Schauer, Stacy A Brethauer, Ali Aminian
Obesity and diabetes are associated with deficits in multiple neurocognitive domains and increased risk for dementia. Over the last two decades, there has been a significant increase in bariatric and metabolic surgery worldwide, driven by rising intertwined pandemics of obesity and diabetes, along with improvement in surgical techniques. Patients undergoing bariatric surgery achieve a significant decrease in their excess weight and a multitude of sequela associated with obesity, diabetes, and metabolic syndrome...
July 2017: Medical Hypotheses
Ayat M Domouky, Ashraf S Hegab, Amal Al-Shahat, Nermin Raafat
BACKGROUND: Diabetes mellitus has become the third human killer following cancer and cardiovascular disease. Millions of patients, often children, suffer from type 1 diabetes (T1D). Stem cells created hopes to regenerate damaged body tissues and restore their function. AIM: This work aimed at clarifying and comparing the therapeutic potential of differentiated and non-differentiated mesenchymal stem cells (MSCs) as a new line of therapy for T1D. METHODS: 40 Female albino rats divided into group I (control): 10 rats and group II (diabetic), III and IV, 10 rats in each, were injected with streptozotocin (50mg/kg body weight)...
April 3, 2017: International Journal of Biochemistry & Cell Biology
Aaron R Cox, Carol J Lam, Matthew M Rankin, Jacqueline S Rios, Julia Chavez, Claire W Bonnyman, Kourtney B King, Roger A Wells, Deepti Anthony, Justin X Tu, Jenny J Kim, Changhong Li, Jake A Kushner
The impact of incretins upon pancreatic β-cell expansion remains extremely controversial. Multiple studies indicate that incretin-based therapies can increase β-cell proliferation, and incretins have been hypothesized to expand β-cell mass. However, disagreement exists on whether incretins increase β-cell mass. Moreover, some reports indicate that incretins may cause metaplastic changes in pancreatic histology. To resolve these questions, we treated a large cohort of mice with incretin-based therapies and carried out a rigorous analysis of β-cell turnover and pancreatic histology using high-throughput imaging...
June 1, 2017: Endocrinology
Carol J Lam, Daniel R Jacobson, Matthew M Rankin, Aaron R Cox, Jake A Kushner
Context: The cellular basis of persistent β-cell function in type 1 diabetes (T1D) remains enigmatic. No extensive quantitative β-cell studies of T1D pancreata have been performed to test for ongoing β-cell regeneration or neogenesis. Objective: We sought to determine the mechanism of β-cell persistence in T1D pancreata. Design: We studied T1D (n = 47) and nondiabetic control (n = 59) pancreata over a wide range of ages from the Juvenile Diabetes Research Foundation Network of Pancreatic Organ Donors with Diabetes via high-throughput microscopy...
August 1, 2017: Journal of Clinical Endocrinology and Metabolism
Nouha Ben-Othman, Andhira Vieira, Monica Courtney, Fabien Record, Elisabet Gjernes, Fabio Avolio, Biljana Hadzic, Noémie Druelle, Tiziana Napolitano, Sergi Navarro-Sanz, Serena Silvano, Keith Al-Hasani, Anja Pfeifer, Sandra Lacas-Gervais, Gunter Leuckx, Laura Marroquí, Julien Thévenet, Ole Dragsbaek Madsen, Decio Laks Eizirik, Harry Heimberg, Julie Kerr-Conte, François Pattou, Ahmed Mansouri, Patrick Collombat
The recent discovery that genetically modified α cells can regenerate and convert into β-like cells in vivo holds great promise for diabetes research. However, to eventually translate these findings to human, it is crucial to discover compounds with similar activities. Herein, we report the identification of GABA as an inducer of α-to-β-like cell conversion in vivo. This conversion induces α cell replacement mechanisms through the mobilization of duct-lining precursor cells that adopt an α cell identity prior to being converted into β-like cells, solely upon sustained GABA exposure...
January 12, 2017: Cell
Sara S Roscioni, Adriana Migliorini, Moritz Gegg, Heiko Lickert
Although β-cell heterogeneity was discovered more than 50 years ago, the underlying principles have been explored only during the past decade. Islet-cell heterogeneity arises during pancreatic development and might reflect the existence of distinct populations of progenitor cells and the developmental pathways of endocrine cells. Heterogeneity can also be acquired in the postnatal period owing to β-cell plasticity or changes in islet architecture. Furthermore, β-cell neogenesis, replication and dedifferentiation represent alternative sources of β-cell heterogeneity...
September 2, 2016: Nature Reviews. Endocrinology
Ansarullah, Colette Free, Jenica Christopherson, Quanhai Chen, Jie Gao, Chengyang Liu, Ali Naji, Alex Rabinovitch, Zhiguang Guo
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...
2016: Journal of Diabetes Research
Hyo-Sup Kim, Moon-Kyu Lee
Pancreatic progenitor cell research has been in the spotlight, as these cells have the potential to replace pancreatic β-cells for the treatment of type 1 and 2 diabetic patients with the absence or reduction of pancreatic β-cells. During the past few decades, the successful treatment of diabetes through transplantation of the whole pancreas or isolated islets has nearly been achieved. However, novel sources of pancreatic islets or insulin-producing cells are required to provide sufficient amounts of donor tissues...
May 2016: Journal of Diabetes Investigation
Ahmed A M Abdel-Hamid, Alaa El-Din L Firgany
Hydroxychloroquine (HCQ) has been demonstrated to reduce the risk to develop diabetes mellitus (DM). However no previous experimental study had investigated its effect on the structure of the endocrine pancreas, islets of Langerhans (IOL), in insulin resistance (IR). In addition, the mechanism by which HCQ can prevent DM is not well understood. In this study, we hypothesized that the possible favorable outcome of HCQ may be partly achieved by its molecular effect on the endothelial stress markers as well as on the imparied balance of the adipokines that usually accompanies IR...
July 2016: Acta Histochemica
László Gerő
In type 1 diabetic patients perfect normoglycaemia can only be achieved by successful transplantation of the pancreas or Langerhans' islets. Surgical transplantation of the whole pancreas is an invasive operation exerting great burden on the patients. Transplantation of the islets of Langerhans does not burden the patients but the survival of the islet grafts is limited. Both interventions are hampered by the lack of donor organs. However, much of these difficulties could be overcome by the use of "artificial β-cells" which ought to have an ultrastructure identical with that of natural β-cells and produce and secrete insulin in a glucose dependent manner...
May 8, 2016: Orvosi Hetilap
Krishna Prasadan, Chiyo Shiota, Xiao Xiangwei, David Ricks, Joseph Fusco, George Gittes
The insulin-secreting beta cells in the endocrine pancreas regulate blood glucose levels, and loss of functional beta cells leads to insulin deficiency, hyperglycemia (high blood glucose) and diabetes mellitus. Current treatment strategies for type-1 (autoimmune) diabetes are islet transplantation, which has significant risks and limitations, or normalization of blood glucose with insulin injections, which is clearly not ideal. The type-1 patients can lack insulin counter-regulatory mechanism; therefore, hypoglycemia is a potential risk...
October 2016: Cellular and Molecular Life Sciences: CMLS
Gloria Baena-Nieto, Isabel M Lomas-Romero, Rosa M Mateos, Noelia Leal-Cosme, Gonzalo Perez-Arana, Manuel Aguilar-Diosdado, Carmen Segundo, Alfonso M Lechuga-Sancho
BACKGROUND: Ghrelin is a peptide hormone with pleiotropic effects. It stimulates cell proliferation and inhibits apoptosis-mediated cell death. It prevents diabetes mellitus in several models of chemical, surgical and biological toxic insults to pancreas in both in vivo and in vitro models and promotes glucose-stimulated insulin secretion under cytotoxic conditions. It has not yet been tested in vivo in an autoimmune model of diabetes with a persistent insult to the β-cell. Given the immunomodulating effects of ghrelin and its trophic effects on β-cells, we hypothesized that ghrelin treatment during the early stages of insulitis would delay diabetes onset...
January 2017: Diabetes/metabolism Research and Reviews
Binhai Ren, Chang Tao, Margaret Anne Swan, Nichole Joachim, Rosetta Martiniello-Wilks, Najah T Nassif, Bronwyn A O'Brien, Ann M Simpson
Due to the limitations of current treatment regimes, gene therapy is a promising strategy being explored to correct blood glucose concentrations in diabetic patients. In the current study, we used a retroviral vector to deliver either the human insulin gene alone, the rat NeuroD1 gene alone, or the human insulin gene and rat NeuroD1 genes together, to the rat liver cell line, H4IIE, to determine if storage of insulin and pancreatic transdifferentiation occurred. Stable clones were selected and expanded into cell lines: H4IIEins (insulin gene alone), H4IIE/ND (NeuroD1 gene alone), and H4IIEins/ND (insulin and NeuroD1 genes)...
April 8, 2016: International Journal of Molecular Sciences
Susan Bonner-Weir, Cristina Aguayo-Mazzucato, Gordon C Weir
After birth the endocrine pancreas continues its development, a complex process that involves both the maturation of islet cells and a marked expansion of their numbers. New beta cells are formed both by duplication of pre-existing cells and by new differentiation (neogenesis) across the first postnatal weeks, with the result of beta cells of different stages of maturation even after weaning. Improving our understanding of this period of beta cell expansion could provide valuable therapeutic insights.
May 2016: Upsala Journal of Medical Sciences
Philippe A Lysy, Elisa Corritore, Etienne M Sokal
Since insulin discovery, islet transplantation was the first protocol to show the possibility to cure patients with type 1 diabetes using low-risk procedures. The scarcity of pancreas donors triggered a burst of studies focused on the production of new β cells in vitro. These were rapidly dominated by pluripotent stem cells (PSCs) demonstrating diabetes-reversal potential in diabetic mice. Subsequent enthusiasm fostered a clinical trial with immunoisolated embryonic-derived pancreatic progenitors. Yet safety is the Achilles' heel of PSCs, and a whole branch of β cell engineering medicine focuses on transdifferentiation of adult pancreatic cells...
May 2016: Current Diabetes Reports
Ahmed A M Abdel-Hamid, Alaa El-Din L El-Firgany
Hydroxychloroquine (HCQ) is supposed to have favorable effects in diabetes mellitus (DM). However no previous experimental studies had investigated its effect on the structure of the endocrine pancreas, islets of Langerhans (IOL), in DM. In addition, the mechanism by which HCQ acts in DM is not well understood. In this study, we hypothesized that the possible favorable effects of HCQ in DM at the structural as well as at metabolic levels could be accomplished, in part, by its anti-inflammatory action. A total of 45 rats were divided equally into; control, DM and HCQ + DM groups (received citrate buffer, 27...
April 2016: Journal of Molecular Histology
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