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Pancreatic beta cells hyperplasia

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https://www.readbyqxmd.com/read/27813705/increased-proliferation-of-the-pancreatic-duct-gland-compartment-in-type-1-diabetes
#1
Abu Saleh Md Moin, Peter C Butler, Alexandra E Butler
CONTEXT: Pancreatic duct glands (PDGs) have been proposed as a source of regeneration in response to exocrine pancreas injury, and thus may serve as an organ stem cell niche. There is evidence to suggest ongoing beta-cell formation in longstanding type 1 diabetes (T1D), but the source is unknown. OBJECTIVE: To investigate the pancreatic duct gland (PDG) compartment of the pancreas in humans with T1D for evidence of an active regenerative signature (presence of progenitor cells and increased proliferation) and, in particular, as a potential source of beta-cells...
November 4, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27576200/activation-of-the-wnt-%C3%AE-catenin-pathway-in-pancreatic-beta-cells-during-the-compensatory-islet-hyperplasia-in-prediabetic-mice
#2
D A Maschio, R B Oliveira, M R Santos, C P F Carvalho, H C L Barbosa-Sampaio, C B Collares-Buzato
The Wnt/β-catenin signaling pathway, also known as the canonical Wnt pathway, plays a role in cell proliferation and differentiation in several tissues/organs. It has been recently described in humans a relationship between type 2 diabetes (T2DM) and mutation in the gene encoding the transcription factor TCF7L2 associated to the Wnt/β-catenin pathway. In the present study, we demonstrated that hyperplastic pancreatic islets from prediabetic mice fed a high-fat diet (HFD) for 60 d displayed nuclear translocation of active β-catenin associated with significant increases in protein content and gene expression of β-catenin as well as of cyclins D1, D2 and c-Myc (target genes of the Wnt pathway) but not of Tcf7l2 (the transcription factor)...
September 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27562401/impact-of-proton-pump-inhibitor-treatment-on-pancreatic-beta-cell-area-and-beta-cell-proliferation-in-humans
#3
Thomas G K Breuer, Laura Borker, Daniel R Quast, Andrea Tannapfel, Wolfgang E Schmidt, Waldemar Uhl, Juris J Meier
INTRODUCTION: Gastrin has been shown to promote beta-cell proliferation in rodents, but its effects in adult humans are largely unclear. Proton pump inhibitors (PPIs) lead to endogenous hypergastrinaemia, and improved glucose control during PPI therapy has been reported in patients with diabetes. Therefore, we addressed whether PPI treatment is associated with improved glucose homoeostasis, islet cell hyperplasia or increased new beta-cell formation in humans. PATIENTS AND METHODS: Pancreatic tissue specimens from 60 patients with and 33 patients without previous PPI therapy were examined...
November 2016: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27057885/successful-medical-treatment-of-adult-nesidioblastosis-with-pasireotide-over-3-years-a-case-report
#4
Verena Schwetz, Karl Horvath, Patrizia Kump, Carolin Lackner, Aurel Perren, Flavio Forrer, Thomas R Pieber, Gerlies Treiber, Harald Sourij, Julia K Mader
Nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. Diagnosis is often challenging and therapeutic options are scarce.In 2009, a 46-year-old female patient presented with recurrent severe hypoglycemia and immediate recovery after glucose ingestion. Although 72-h-fasting test was positive, various imaging technologies (sonography, computed tomography, somatostatin receptor scintigraphy, dopamine receptor positron emission tomography [DOPA-PET]) were negative. Endoscopic ultrasound revealed a lesion in the pancreatic corpus, whereas selective arterial calcium stimulation test, portal venous sampling and GLP-1-receptor scintigraphy were indicative of a lesion in the pancreatic tail, which was surgically removed...
April 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/26534984/inactivating-the-permanent-neonatal-diabetes-gene-mnx1-switches-insulin-producing-%C3%AE-cells-to-a-%C3%AE-like-fate-and-reveals-a-facultative-proliferative-capacity-in-aged-%C3%AE-cells
#5
Fong Cheng Pan, Marcela Brissova, Alvin C Powers, Samuel Pfaff, Christopher V E Wright
Homozygous Mnx1 mutation causes permanent neonatal diabetes in humans, but via unknown mechanisms. Our systematic and longitudinal analysis of Mnx1 function during murine pancreas organogenesis and into the adult uncovered novel stage-specific roles for Mnx1 in endocrine lineage allocation and β-cell fate maintenance. Inactivation in the endocrine-progenitor stage shows that Mnx1 promotes β-cell while suppressing δ-cell differentiation programs, and is crucial for postnatal β-cell fate maintenance. Inactivating Mnx1 in embryonic β-cells (Mnx1(Δbeta)) caused β-to-δ-like cell transdifferentiation, which was delayed until postnatal stages...
November 1, 2015: Development
https://www.readbyqxmd.com/read/26276744/modulation-of-breast-cancer-risk-biomarkers-by-high-dose-omega-3-fatty-acids-phase-ii-pilot-study-in-postmenopausal-women
#6
Carol J Fabian, Bruce F Kimler, Teresa A Phillips, Jennifer L Nydegger, Amy L Kreutzjans, Susan E Carlson, Brandon H Hidaka, Trina Metheny, Carola M Zalles, Gordon B Mills, Kandy R Powers, Debra K Sullivan, Brian K Petroff, Whitney L Hensing, Brooke L Fridley, Stephen D Hursting
Associational studies suggest higher intakes/blood levels of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid (AA) are associated with reduced breast cancer risk. We performed a pilot study of high-dose EPA + DHA in postmenopausal women to assess feasibility before initiating a phase IIB prevention trial. Postmenopausal women with cytologic evidence of hyperplasia in their baseline random periareolar fine needle aspiration (RPFNA) took 1,860 mg EPA +1500 mg DHA ethyl esters daily for 6 months...
October 2015: Cancer Prevention Research
https://www.readbyqxmd.com/read/26236746/delta-cell-hyperplasia-in-adult-goto-kakizaki-gk-moltac-diabetic-rats
#7
Lukáš Alán, Tomáš Olejár, Monika Cahová, Jaroslav Zelenka, Zuzana Berková, Magdalena Smětáková, František Saudek, Radoslav Matěj, Petr Ježek
Reduced beta cell mass in pancreatic islets (PI) of Goto-Kakizaki (GK) rats is frequently observed in this diabetic model, but knowledge on delta cells is scarce. Aiming to compare delta cell physiology/pathology of GK to Wistar rats, we found that delta cell number increased over time as did somatostatin mRNA and delta cells distribution in PI is different in GK rats. Subtle changes in 6-week-old GK rats were found. With maturation and aging of GK rats, disturbed cytoarchitecture occurred with irregular beta cells accompanied by delta cell hyperplasia and loss of pancreatic polypeptide (PPY) positivity...
2015: Journal of Diabetes Research
https://www.readbyqxmd.com/read/26051303/fetal-endocrine-therapy-for-congenital-adrenal-hyperplasia-should-not-be-done
#8
REVIEW
Walter L Miller
Prenatal treatment of congenital adrenal hyperplasia by administering dexamethasone to a woman presumed to be carrying an at-risk fetus remains a controversial experimental treatment. Review of data from animal experimentation and human trials indicates that dexamethasone cannot be considered safe for the fetus. In animals, prenatal dexamethasone decreases birth weight, affects renal, pancreatic beta cell and brain development, increases anxiety and predisposes to adult hypertension and hyperglycemia. In human studies, prenatal dexamethasone is associated with orofacial clefts, decreased birth weight, poorer verbal working memory, and poorer self-perception of scholastic and social competence...
June 2015: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/25811804/loss-of-fibroblast-growth-factor-21-action-induces-insulin-resistance-pancreatic-islet-hyperplasia-and-dysfunction-in-mice
#9
W Y So, Q Cheng, A Xu, K S L Lam, P S Leung
Fibroblast growth factor (FGF) 21 is an endocrine factor that normalizes glucose homeostasis and reduces insulin resistance in diabetes. Although the pancreas is an FGF21 target organ, its role in pancreatic islets remains obscure. This study aimed to elucidate the physiological role of FGF21 in pancreatic islets using FGF21-knockout (FGF21-KO) mice. Twenty-four-week-old male global FGF21-KO mice were used in this study. Glucose and insulin tolerance were assessed. Expression of genes and proteins related to islet function and underlying mechanisms were also examined...
2015: Cell Death & Disease
https://www.readbyqxmd.com/read/25797178/insulin-receptor-isoform-a-confers-a-higher-proliferative-capability-to-pancreatic-beta-cells-enabling-glucose-availability-and-igf-i-signaling
#10
Oscar Escribano, Almudena Gómez-Hernández, Sabela Díaz-Castroverde, Carmen Nevado, Gema García, Yolanda F Otero, Liliana Perdomo, Nuria Beneit, Manuel Benito
The main compensatory response to insulin resistance is the pancreatic beta cell hyperplasia to account for increased insulin secretion. In fact, in a previous work we proposed a liver-pancreas endocrine axis with IGF-I (insulin-like growth factor type I) secreted by the liver acting on IRA insulin receptor in beta cells from iLIRKO mice (inducible Liver Insulin Receptor KnockOut) that showed a high IRA/IRB ratio. However, the role of insulin receptor isoforms in the IGF-I-induced beta cell proliferation as well as the underlying molecular mechanisms remain poorly understood...
July 5, 2015: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/25774199/development-of-multifocal-nodular-lesions-of-a-liver-mimicking-hepatic-metastasis-following-resection-of-an-insulinoma-in-a-child
#11
Sook Young Jung, Ben Kang, Yoon Mee Choi, Jun Mee Kim, Soon Ki Kim, Young Se Kwon, Ji Eun Lee
Insulinoma, which arises from insulin-producing pancreatic beta cells, is a rare tumor in children. Only 5%-10% of insulinomas are malignant and undergo metastasis. We report a case of an 11-year-old girl who experienced hypoglycemia-related seizures induced by an insulinoma; after resection of the primary tumor, she developed hepatic focal nodular hyperplasia (FNH). Laboratory test results indicated marked hypoglycemia with hyperinsulinemia. Abdominal ultrasonography (US) and computed tomography results were normal; however, magnetic resonance imaging (MRI) showed a solid mass in the pancreatic tail...
February 2015: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/24755752/-a-case-of-alpha-cell-nesidioblastosis-and-hyperplasia-with-multiple-glucagon-producing-endocrine-cell-tumor-of-the-pancreas
#12
Huapyong Kang, Sewha Kim, Tae Seop Lim, Hye Won Lee, Heun Choi, Chang Moo Kang, Ho Guen Kim, Seungmin Bang
Nesidioblastosis is a term used to describe pathologic overgrowth of pancreatic islet cells. It also means maldistribution of islet cells within the ductules of exocrine pancreas. Generally, nesidioblastosis occurs in beta-cell and causes neonatal hyperinsulinemic hypoglycemia or adult noninsulinoma pancreatogenous hypoglycemia syndrome. Alpha-cell nesidioblastosis and hyperplasia is an extremely rare disorder. It often accompanies glucagon-producing marco- and mircoadenoma without typical glucagonoma syndrome...
April 2014: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/24733160/the-nucleotide-exchange-factor-sil1-is-required-for-glucose-stimulated-insulin-secretion-from-mouse-pancreatic-beta-cells-in-vivo
#13
Arne A Ittner, Josefine Bertz, Tse Yan Becky Chan, Janet van Eersel, Patsie Polly, Lars M Ittner
AIMS/HYPOTHESIS: Regulation of insulin secretion along the secretory pathway is incompletely understood. We addressed the expression of SIL1, a nucleotide exchange factor for the endoplasmic reticulum (ER) chaperone glucose-regulated protein 78 kD (GRP78), in pancreatic beta cells and investigated whether or not SIL1 is involved in beta cell function. METHODS: SIL1 expression was analysed by immunoblotting and immunofluorescence. Metabolic and islet variables, including glucose tolerance, beta cell mass, insulin secretion, islet ultrastructure, insulin content and levels of ER stress marker proteins, were addressed in Sil1 knockout (Sil1 (-/-)) mice...
July 2014: Diabetologia
https://www.readbyqxmd.com/read/24173297/obesity-and-diabetes-mellitus-with-striking-congenital-hyperplasia-of-the-islets-of-langerhans-in-spiny-mice-acomys-cahirinus-i-histological-findings-and-preliminary-metabolic-observations
#14
A E Gonet, W Stauffacher, R Pictet, A E Renold
Spiny mice (Acomys) are a group of small rodents indigenous to the Eastern Mediterranean and Africa. The Acomys Cahirinus strain reported on here is indigenous to Israel. The strain is characterized by striking and congenital hyperplasia of the islets of Langerhans, primarily of the beta cells. The endocrine tissue contributes up to 15 per cent of the pancreatic mass in adults, up to 25 per cent in the newborn. Pancreatic insulin content may be as high as 100 units per gram wet weight. When fedad libitum in the laboratory approximately one-half of the animals become obese, while approximately 15 per cent develop a diabetes mellitus-like state with moderate hyperglycemia, glucosuria, and, less frequently, ketonuria accompanied by weight loss and, ultimately, death...
April 1966: Diabetologia
https://www.readbyqxmd.com/read/24075522/nesidioblastosis-a-case-of-hyperplasia-of-the-islets-of-langerhans-in-the-adult
#15
Esther Pilar García-Santos, María del Carmen Manzanares-Campillo, David Padilla-Valverde, Pedro Villarejo-Campos, Aurora Gil-Rendo, Virginia Muñoz-Atienza, Susana Sánchez-García, Ana María Puig-Rullán, José Luis Rodríguez-Peralto, Jesús Martín-Fernández
INTRODUCTION: Nesidioblastosis is a rare disease caused by hyperplasia of pancreatic islets, developing a state of hypoglycemia due to an increase in the insulin production. It is the leading cause of hyperinsulinic hypoglycemia in childhood, whereas in adults it only represents the 0.5-5% of cases. The pathogenesis is still unknown. We have studied several genetic mutations associated with dependent potassium channel of ATP present in the beta cells of the pancreas, as well as in patients underwent bariatric surgery because of the metabolic changes involved...
September 2013: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/24068386/smad2-disruption-in-mouse-pancreatic-beta-cells-leads-to-islet-hyperplasia-and-impaired-insulin-secretion-due-to-the-attenuation-of-atp-sensitive-k-channel-activity
#16
Masatoshi Nomura, Hai-Lei Zhu, Lixiang Wang, Hidetaka Morinaga, Ryoichi Takayanagi, Noriyoshi Teramoto
AIMS/HYPOTHESIS: The TGF-β superfamily of ligands provides important signals for the development of pancreas islets. However, it is not yet known whether the TGF-β family signalling pathway is required for essential islet functions in the adult pancreas. METHODS: To identify distinct roles for the downstream components of the canonical TGF-β signalling pathway, a Cre-loxP system was used to disrupt SMAD2, an intracellular transducer of TGF-β signals, in pancreatic beta cells (i...
January 2014: Diabetologia
https://www.readbyqxmd.com/read/23344951/hyperplasia-of-pancreatic-beta-cells-and-improved-glucose-tolerance-in-mice-deficient-in-the-fxyd2-subunit-of-na-k-atpase
#17
Elena Arystarkhova, Yi B Liu, Cynthia Salazar, Violeta Stanojevic, Rebecca J Clifford, Jack H Kaplan, Gerald M Kidder, Kathleen J Sweadner
Restoration of the functional potency of pancreatic islets either through enhanced proliferation (hyperplasia) or increase in size (hypertrophy) of beta cells is a major objective for intervention in diabetes. We have obtained experimental evidence that global knock-out of a small, single-span regulatory subunit of Na,K-ATPase, FXYD2, alters glucose control. Adult Fxyd2(-/-) mice showed significantly lower blood glucose levels, no signs of peripheral insulin resistance, and improved glucose tolerance compared with their littermate controls...
March 8, 2013: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/23123167/prenatal-treatment-of-congenital-adrenal-hyperplasia-risks-outweigh-benefits
#18
Walter L Miller, Selma Feldman Witchel
Prenatal treatment of congenital adrenal hyperplasia by administering dexamethasone to a woman presumed to be carrying an at-risk fetus has been described as safe and effective in several reports. A review of data from animal experimentation and human trials indicates that first-trimester dexamethasone decreases birthweight; affects renal, pancreatic beta cell, and brain development; increases anxiety; and predisposes to adult hypertension and hyperglycemia. In human studies, first-trimester dexamethasone is associated with orofacial clefts, decreased birthweight, poorer verbal working memory, and poorer self-perception of scholastic and social competence...
May 2013: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/22095234/early-insulin-therapy-prevents-beta-cell-loss-in-a-mouse-model-for-permanent-neonatal-diabetes-munich-ins2-c95s
#19
S Kautz, L van Bürck, M Schuster, E Wolf, R Wanke, N Herbach
AIMS: Heterozygous male Munich Ins2(C95S) mutant mice, a model for permanent neonatal diabetes mellitus, demonstrate a progressive diabetic phenotype with severe loss of functional beta cell mass. The aim of this study was to investigate the influence of early insulin treatment on glucose homeostasis and beta cell destruction in male Munich Ins2(C95S) mutants. METHODS: One group of male Ins2(C95S) mutants was treated with subcutaneous insulin pellets, as soon as blood glucose levels began to rise; placebo-treated mutants and wild-type mice served as controls...
February 2012: Diabetologia
https://www.readbyqxmd.com/read/21617177/thrombospondin-1-an-islet-endothelial-cell-signal-of-importance-for-%C3%AE-cell-function
#20
Johan Olerud, Dariush Mokhtari, Magnus Johansson, Gustaf Christoffersson, Jack Lawler, Nils Welsh, Per-Ola Carlsson
OBJECTIVE: Loss of thrombospondin (TSP)-1 in pancreatic islets has been shown to cause islet hyperplasia. This study tested the hypothesis that endothelial-derived TSP-1 is important for β-cell function. RESEARCH DESIGN AND METHODS: Islet function was evaluated both in vivo and in vitro. Messenger RNA and protein expression were measured by real-time PCR and Western blot, respectively. The role of endothelial-derived TSP-1 for β-cell function was determined using a transplantation design in which recipient blood vessels either were allowed to grow or not into the transplanted islets...
July 2011: Diabetes
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