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https://www.readbyqxmd.com/read/28432571/cell-therapy-for-type-1-diabetes-current-and-future-strategies
#1
REVIEW
Yasaman Aghazadeh, Maria Cristina Nostro
PURPOSE OF THE REVIEW: Type 1 diabetes (T1D) is defined by an autoimmune destruction of insulin producing β-cells located in the endocrine part of the pancreas, the islets of Langerhans. As exogenous insulin administration fails at preventing severe complications associated with this disease, cell replacement therapies are being considered as a means to treat T1D. The purpose of this manuscript is to review the challenges associated with current strategies and discuss the potential of stem cell therapy for the treatment of T1D...
June 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28429491/bringing-the-human-pancreas-into-focus-new-paradigms-for-the-understanding-of-type-1-diabetes
#2
REVIEW
N G Morgan
Type 1 diabetes affects increasingly large numbers of people globally (including at least half a million children under the age of 14 years) and it remains an illness with life-long and often devastating consequences. It is surprising, therefore, that the underlying aetiology of Type 1 diabetes remains poorly understood. This is largely because the cellular and molecular processes leading to the loss of β cells in the pancreas have rarely been studied at, or soon after, the onset of disease. Where such studies have been undertaken, a number of surprises have emerged which serve to challenge conventional wisdom...
April 20, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28426078/an-intravascular-bioartificial-pancreas-device-ibap-with-silicon-nanopore-membranes-snm-for-islet-encapsulation-under-convective-mass-transport
#3
Shang Song, Charles Blaha, Willieford Moses, Jaehyun Park, Nathan Wright, Joey Groszek, William Fissell, Shant Vartanian, Andrew M Posselt, Shuvo Roy
Diffusion-based bioartificial pancreas (BAP) devices are limited by poor islet viability and functionality due to inadequate mass transfer resulting in islet hypoxia and delayed glucose-insulin kinetics. While intravascular ultrafiltration-based BAP devices possess enhanced glucose-insulin kinetics, the polymer membranes used in these devices provide inadequate ultrafiltrate flow rates and result in excessive thrombosis. Here, we report the silicon nanopore membrane (SNM), which exhibits a greater hydraulic permeability and a superior pore size selectivity compared to polymer membranes for use in BAP applications...
April 20, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28422431/effect-of-empagliflozin-on-tacrolimus-induced-pancreas-islet-dysfunction-and-renal-injury
#4
J Jin, L Jin, K Luo, S W Lim, B H Chung, C W Yang
An inhibitor of sodium glucose co-transporter type 2 (SGLT-2) is recommended in type 2 diabetes mellitus (DM) but its use is still undetermined in Tacrolimus (TAC)-induced DM. We evaluated the effect of empagliflozin (Em) on TAC-induced pancreatic islet dysfunction and renal injury in experimental model of TAC-induced DM and in vitro. TAC induced a two-fold increase in SGLT-2 expression, while Em decreased SGLT-2 expression and further increased urinary glucose excretion compared to the TAC group. Em reduced hyperglycemia and increased plasma insulin level, pancreatic islet size and glucose-stimulated insulin secretion (GSIS) compared to the TAC group...
April 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28420858/transcriptional-regulation-of-pancreas-development-and-%C3%AE-cell-function-review
#5
Yoshio Fujitani
A small number of cells in the adult pancreas are endocrine cells. They are arranged in clusters called islets of Langerhans. The islets make insulin, glucagon, and other endocrine hormones, and release them into the blood circulation. These hormones help control the level of blood glucose. Therefore, a dysfunction of endocrine cells in the pancreas results in impaired glucose homeostasis, or diabetes mellitus. The pancreas is an organ that originates from the evaginations of pancreatic progenitor cells in the epithelium of the forgut endoderm...
April 14, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28419211/the-inhibitory-g-protein-%C3%AE-subunit-g%C3%AE-z-promotes-type-1-diabetes-like-pathophysiology-in-nod-mice
#6
Rachel J Fenske, Mark T Cadena, Quincy E Harenda, Haley N Wienkes, Kathryn Carbajal, Michael D Schaid, Erin Laundre, Allison L Brill, Nathan A Truchan, Harpreet Brar, Jaclyn Wisinski, Jinjin Cai, Timothy E Graham, Feyza Engin, Michelle E Kimple
The alpha subunit of the heterotrimeric Gz protein, Gαz, promotes beta-cell death and inhibits beta-cell replication when pancreatic islets are challenged by stressors. Thus, we hypothesized that loss of Gαz protein would preserve functional beta-cell mass in the non-obese diabetic (NOD) model, protecting from overt diabetes. We saw that protection from diabetes was robust and durable up to 35 weeks of age in Gαz knockout mice. By 17 weeks of age, Gαz-null NOD mice had significantly higher diabetes-free survival than wild-type littermates...
April 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28409821/nano-curcumin-safely-prevents-streptozotocin-induced-inflammation-and-apoptosis-in-pancreatic-%C3%A3-cells-for-effective-management-of-type-1-diabetes-mellitus
#7
Raghu Ganugula, Meenakshi Arora, Patcharawalai Jaisamut, Ruedeekorn Wiwattanapatapee, Heather G Jørgensen, Vinod P Venkatpurwar, Beiyan Zhou, Aline Rodrigues Hoffmann, Rita Basu, Shaodong Guo, Majeti N V Ravi Kumar
BACKGROUND AND PURPOSE: Approaches to prevent selective and progressive loss of insulin-producing ß-cells in Type 1 diabetes mellitus (T1DM) will help conquer this prevalent and devastating disease. Curcumin (CUR), a natural anti-inflammatory, suppresses diabetes associated inflammation and cell death. However, very high doses have been tested owing to poor oral bioavailability, making it difficult to translate to the clinic. EXPERIMENTAL APPROACH: We recently prepared biodegradable nanosystems encapsulating curcumin (nCUR), resulting in at least 9-fold improvement in oral bioavailability...
April 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28398495/a-histological-study-of-fulminant-type-1-diabetes-mellitus-related-to-human-cytomegalovirus-reactivation
#8
Sho Yoneda, Akihisa Imagawa, Kenji Fukui, Sae Uno, Junji Kozawa, Makoto Sakai, Toshiki Yumioka, Hiromi Iwahashi, Iichiro Shimomura
Context: Fulminant type 1 diabetes mellitus (T1DM) is thought to be partly caused by virus infection. Objective: This study investigated the mechanism of β cell destruction in fulminant T1DM after drug-induced hypersensitivity syndrome (DIHS). Methods: We determined the localization of viruses of human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV), and the expression of interferon regulatory factor 3 (IRF3) and viral receptors of Z DNA binding protein 1 (ZBP1) and retinoic acid-inducible gene I (RIG-I), together with inflammatory cells by immunohistochemistry of pancreas from an autopsy fulminant T1DM patient with DIHS or seven subjects with normal glucose tolerance who underwent pancreatectomy...
April 10, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28397308/improvement-of-isolated-caprine-islet-survival-and-functionality-in-vitro-by-enhancing-of-pdx1-gene-expression
#9
Homayoun Hani, Zeenathul Nazariah Allaudin, Mohd-Azmi Mohd-Lila, Kazhal Sarsaifi, Mina Rasouli, Yew Joon Tam, Tengku-Azmi Tengku-Ibrahim, Abas Mazni Othman
BACKGROUND: Dead islets replaced with viable islets are a promising offer to restore normal insulin production to a person with diabetes. The main reason for establishing a new islet source for transplantation is the insufficiency of human donor pancreas while using xenogeneic islets perhaps assists this problem. The expression of PDX1 is essential for the pancreas expansion. In mature β-cells, PDX1 has several critical roles such as glucose sensing, insulin synthesis, and insulin secretion...
April 11, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28397049/atp-synthase-%C3%AE-subunit-abnormality-in-pancreas-islets-of-rats-with-polycystic-ovary-syndrome-and-type-2-diabetes-mellitus
#10
Wei Li, Sai-Jiao Li, Tai-Lang Yin, Jing Yang, Yan Cheng
This study investigated the abnormal expression of ATP synthase β-subunit (ATPsyn-β) in pancreas islets of rat model of polycystic ovary syndrome (PCOS) with type 2 diabetes mellitus (T2DM), and the secretion function changes after up-regulation of ATP5b. Sixty female SD rats were divided into three groups randomly and equally. The rat model of PCOS with T2DM was established by free access to the high-carbohydrate/high-fat diet, subcutaneous injections of DHEA, and a single injection of streptozotocin. The pancreas was removed for the detection of the ATPsyn-β expression by immunohistochemical staining, Western blotting and reverse transcription-PCR (RT-PCR)...
April 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28393070/assessment-of-toxicological-perturbations-and-variants-of-pancreatic-islet-development-in-the-zebrafish-model
#11
Karilyn E Sant, Haydee M Jacobs, Jiali Xu, Katrina A Borofski, Larry G Moss, Jennifer B Moss, Alicia R Timme-Laragy
The pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue of chemical exposures. However, this endpoint, as well as the integrity of the surrounding exocrine pancreas, is often overlooked in studies of developmental toxicology. Disruption of development by toxicants can alter cell fate and migration, resulting in structural alterations that are difficult to detect in mammalian embryo systems, but that are easily observed in the zebrafish embryo model (Danio rerio)...
September 2016: Toxics
https://www.readbyqxmd.com/read/28386438/expression-and-function-of-atp-dependent-potassium-channels-in-zebrafish-islet-%C3%AE-cells
#12
Christopher H Emfinger, Alecia Welscher, Zihan Yan, Yixi Wang, Hannah Conway, Jennifer B Moss, Larry G Moss, Maria S Remedi, Colin G Nichols
ATP-sensitive potassium channels (KATP channels) are critical nutrient sensors in many mammalian tissues. In the pancreas, KATP channels are essential for coupling glucose metabolism to insulin secretion. While orthologous genes for many components of metabolism-secretion coupling in mammals are present in lower vertebrates, their expression, functionality and ultimate impact on body glucose homeostasis are unclear. In this paper, we demonstrate that zebrafish islet β-cells express functional KATP channels of similar subunit composition, structure and metabolic sensitivity to their mammalian counterparts...
February 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28386316/energy-intake-correlates-with-the-levels-of-fatty-acid-synthase-and-insulin-like-growth-factor-1-in-male-and-female-c57bl-6-mice
#13
Anup S Ramdhave, Shreesh Ojha, Mukesh Nandave
Emerging evidence suggests that, dysregulation of fatty acid synthase (FASN) and insulin-like growth factor-1 (IGF-1) could play a vital role in pathology of various diseases. Our aim was to determine the changes in FASN and IGF-1 levels concomitant to long term feeding of HFD in either sex. Male and female mice were fed either HFD or LFD for a period of 16 weeks. During this period, physiological, biochemical, and histological parameters were evaluated. Mice fed with HFD showed a significant gain in body weight, body mass index, energy intake, and abdominal circumference...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28385600/mesenchymal-stem-cells-and-differentiated-insulin-producing-cells-are-new-horizons-for-pancreatic-regeneration-in-type-i-diabetes-mellitus
#14
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
https://www.readbyqxmd.com/read/28385584/a-study-of-the-clinical-utility-of-a-20-minute-secretin-stimulated-endoscopic-pancreas-function-test-and-performance-according-to-clinical-variables
#15
Luis F Lara, Morihito Takita, James S Burdick, Daniel C DeMarco, Ronnie R Pimentel, Tolga Erim, Marlon F Levy
BACKGROUND & AIMS: Direct pancreas juice testing of bicarbonate, lipase, or trypsin after stimulation by secretin or cholecystokinin (CCK) is used to determine exocrine function, a surrogate for diagnosing chronic pancreatitis (CP). Endoscopic pancreas function tests (ePFT) where a peak bicarbonate concentration (PBC) ≥80 mEq/L in pancreas juice is considered normal are now used more frequently. In this ePFT aspirates start 35 minutes after secretin administration because pancreas output peaks 30 minutes after secretagogue administration...
April 3, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/28385175/on-the-role-of-the-gut-in-diabetic-hyperglucagonaemia
#16
Asger Lund
Patients with type 2 diabetes are characterised not only by compromised insulin secretion and action, but also by elevated plasma concentrations of the 29-amino acid peptide hormone glucagon, which generally is thought of as a pancreas-derived hormone (produced in and secreted from alpha cells in the islet of Langerhans). In patients with diabetes, circulating glucagon concentrations are elevated in the fasting state and fail to decrease appropriately or even increase in response to ingestion of nutrients. Glucagon is known to be a potent stimulator of hepatic glucose production, and, thus, the elevated glucagon concentrations in diabetes contribute decisively to the predominating trait of patients with diabetes namely hyperglycaemia...
April 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/28380379/%C3%AE-cell-aging-markers-have-heterogeneous-distribution-and-are-induced-by-insulin-resistance
#17
Cristina Aguayo-Mazzucato, Mark van Haaren, Magdalena Mruk, Terence B Lee, Caitlin Crawford, Jennifer Hollister-Lock, Brooke A Sullivan, James W Johnson, Aref Ebrahimi, Jonathan M Dreyfuss, Jan Van Deursen, Gordon C Weir, Susan Bonner-Weir
We hypothesized that the known heterogeneity of pancreatic β cells was due to subpopulations of β cells at different stages of their life cycle with different functional capacities and that further changes occur with metabolic stress and aging. We identified new markers of aging in β cells, including IGF1R. In β cells IGF1R expression correlated with age, dysfunction, and expression of known age markers p16(ink4a), p53BP1, and senescence-associated β-galactosidase. The new markers showed striking heterogeneity both within and between islets in both mouse and human pancreas...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380367/pancreas-and-not-gut-mediates-the-glp-1-induced-glucoincretin-effect
#18
Joel F Habener, Violeta Stanojevic
The gut is believed to be the source of GLP-1 that augments insulin secretion in response to oral nutrients. In this issue of Cell Metabolism, Chambers et al. (2017) shift the paradigm by finding that GLP-1 produced within the islets of the pancreas, and not the gut, is responsible for the incretin effect in mice.
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380195/duodenal-jejunal-bypass-normalizes-pancreatic-islet-proliferation-rate-and-function-but-not-hepatic-steatosis-in-hypothalamic-obese-rats
#19
K R Cantelli, G M Soares, R A Ribeiro, S L Balbo, C Lubaczeuski, A C Boschero, A C F Araújo, M L Bonfleur
Modifications in life-style and/or pharmacotherapies contribute to weight loss and ameliorate the metabolic profile of diet-induced obese humans and rodents. Since these strategies fail to treat hypothalamic obesity, we have assessed the possible mechanisms by which duodenal-jejunal bypass (DJB) surgery regulates hepatic lipid metabolism and the morphophysiology of pancreatic islets, in hypothalamic obese (HyO) rats. During the first 5 days of life, male Wistar rats received subcutaneous injections of monosodium glutamate (4 g/kg body weight, HyO group), or saline (CTL)...
March 30, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28364316/a-case-of-annular-pancreas-with-wirsung-s-duct-encircling-the-duodenum-embryological-hypothesis-based-on-cholangiopancreatographic-and-immunohistochemical-findings
#20
Manami Fukai, Terumi Kamisawa, Shin-Ichirou Horiguchi, Tsunekazu Hishima, Sawako Kuruma, Kazuro Chiba, Satomi Koizumi, Taku Tabata, Sayaka Nagao, Masataka Kikuyama, Goro Honda, Masanao Kurata
We present a resected case of annular pancreas in which Wirsung's duct encircled the duodenum and continued directly to the main pancreatic duct in the body and tail. Furthermore, Wirsung's duct coursed along the right side of the lower bile duct near the major duodenal papilla. Histologically, the islets of Langerhans in the annular pancreas were irregular in shape and were characterized by a striking abundance of pancreatic polypeptide (PP)-positive cells. The PP-rich area that encircled the duodenum was fused with the PP-poor area in the head of the pancreas...
March 31, 2017: Clinical Journal of Gastroenterology
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