Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia.
Diabetes Care 39(7):1230 (2016)
Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at...
Pseudo-Casimir stresses and elasticity of a confined elastomer film.
Soft Matter 12(19):4384 (2016)
Investigations of the elastic behavior of bulk elastomers have traditionally proceeded on the basis of classical rubber elasticity, which regards chains as thermally fluctuating but disregards the thermal fluctuations of the cross-links. Herein, we consider an incompressible and flat elastomer f...
Integration of ATAC-seq and RNA-seq identifies human alpha cell and beta cell signature genes.
Molecular Metabolism 5(3):233 (2016)
Although glucagon-secreting α-cells and insulin-secreting β-cells have opposing functions in regulating plasma glucose levels, the two cell types share a common developmental origin and exhibit overlapping transcriptomes and epigenomes. Notably, destruction of β-cells can stimulate repopulation ...
Pancreas Transplantation in the Modern Era.
Gastroenterology Clinics of North America 45(1):145 (2016)
The field of pancreas transplantation has evolved from an experimental procedure in the 1980s to become a routine transplant in the modern era. With short- and long-term outcomes continuing to improve and the significant mortality, quality-of-life, and end-organ disease benefits, pancreas transp...
Hydrodynamic fluctuation-induced forces in confined fluids.
Soft Matter 12(2):441 (2016)
We study thermal, fluctuation-induced hydrodynamic interaction forces in a classical, compressible, viscous fluid confined between two rigid, planar walls with no-slip boundary conditions. We calculate hydrodynamic fluctuations using the linearized, stochastic Navier-Stokes formalism of Landau a...
A Multicenter Study: North American Islet Donor Score in Donor Pancreas Selection for Human Islet Isolation for Transplantation.
Cell Transplantation 25(8):1515 (2016)
Selection of an optimal donor pancreas is the first key task for successful islet isolation. We conducted a retrospective multicenter study in 11 centers in North America to develop an islet donor scoring system using donor variables. The data set consisting of 1,056 deceased donors was used for...
TGF-β1 promotes acinar to ductal metaplasia of human pancreatic acinar cells.
Scientific reports 6:30904 (2016)
Animal studies suggest that pancreatitis-induced acinar-to-ductal metaplasia (ADM) is a key event for pancreatic ductal adenocarcinoma (PDAC) initiation. However, there has not been an adequate system to explore the mechanisms of human ADM induction. We have developed a flow cytometry-based, hig...
Activation of GPR119 Stimulates Human β-Cell Replication and Neogenesis in Humanized Mice with Functional Human Islets.
Journal of diabetes research 2016:1620821 (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-) ...
Ion-mediated interactions between net-neutral slabs: Weak and strong disorder effects.
Journal of Chemical Physics 143(23):234701 (2015)
We investigate the effective interaction between two randomly charged but otherwise net-neutral, planar dielectric slabs immersed in an asymmetric Coulomb fluid containing a mixture of mobile monovalent and multivalent ions. The presence of charge disorder on the apposed bounding surfaces of the...
Accumulation of 3-hydroxytetradecenoic acid: Cause or corollary of glucolipotoxic impairment of pancreatic β-cell bioenergetics?
Molecular Metabolism 4(12):926 (2015)
Hyperglycemia and elevated blood lipids are the presumed precipitating causes of β-cell damage in T2DM as the result of a process termed "glucolipotoxicity". Here, we tested whether glucolipotoxic pathophysiology is caused by defective bioenergetics using islets in culture.
Insulin secretion, re...
Bisphosphonate Induces Osteonecrosis of the Jaw in Diabetic Mice via NLRP3/Caspase-1-Dependent IL-1β Mechanism.
Journal of Bone and Mineral Research 30(12):2300 (2015)
Diabetes mellitus is an established risk factor associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ). Sustained activation of Nod-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome contributes to the persistent inflammation and impaired cutaneou...
Molecular recognition by van der Waals interaction between polymers with sequence-specific polarizabilities.
Journal of Chemical Physics 142(21):214904 (2015)
We analyze van der Waals interactions between two rigid polymers with sequence-specific, anisotropic polarizabilities along the polymer backbones, so that the dipole moments fluctuate parallel to the polymer backbones. Assuming that each polymer has a quenched-in polarizability sequence which re...
Strong coupling electrostatics for randomly charged surfaces: antifragility and effective interactions.
Soft Matter 11(17):3441 (2015)
We study the effective interaction mediated by strongly coupled Coulomb fluids between dielectric surfaces carrying quenched, random monopolar charges with equal mean and variance, both when the Coulomb fluid consists only of mobile multivalent counterions and when it consists of an asymmetric i...
Restoration of Glucose Counterregulation by Islet Transplantation in Long-standing Type 1 Diabetes.
Diabetes 64(5):1713 (2015)
Patients with long-standing type 1 diabetes (T1D) may exhibit defective glucose counterregulation and impaired hypoglycemia symptom recognition that substantially increase their risk for experiencing severe hypoglycemia. The purpose of this study was to determine whether intrahepatic islet trans...
Identification of functional variants for cleft lip with or without cleft palate in or near PAX7, FGFR2, and NOG by targeted sequencing of GWAS loci.
The American Journal of Human Genetics 96(3):397 (2015)
Although genome-wide association studies (GWASs) for nonsyndromic orofacial clefts have identified multiple strongly associated regions, the causal variants are unknown. To address this, we selected 13 regions from GWASs and other studies, performed targeted sequencing in 1,409 Asian and Europea...
Fluctuation-induced interactions in nematics with disordered anchoring energy.
Journal of Physics, Condensed Matter 26(50):505101 (2014)
We examine fluctuation-induced (pseudo-Casimir) interactions in nematic liquid-crystalline films confined between two surfaces, where one of the surfaces imposes a strong homeotropic anchoring (ensuring a uniform mean director profile), while the other one is assumed to be a chemically disordere...
Asymmetric Coulomb fluids at randomly charged dielectric interfaces: anti-fragility, overcharging and charge inversion.
Journal of Chemical Physics 141(17):174704 (2014)
We study the distribution of multivalent counterions next to a dielectric slab, bearing a quenched, random distribution of charges on one of its solution interfaces, with a given mean and variance, both in the absence and in the presence of a bathing monovalent salt solution. We use the previous...
Metabolic memory of ß-cells controls insulin secretion and is mediated by CaMKII.
Molecular Metabolism 3(4):484 (2014)
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) functions both in regulation of insulin secretion and neurotransmitter release through common downstream mediators. Therefore, we hypothesized that pancreatic ß-cells acquire and store the information contained in calcium pulses as a form of...
Insulin sensitivity index in type 1 diabetes and following human islet transplantation: comparison of the minimal model to euglycemic clamp measures.
American Journal of Physiology - Endocrinology ... 306(10):E1217 (2014)
Insulin sensitivity is impaired in type 1 diabetes (T1D) and may be enhanced by islet transplantation, an effect best explained by improved metabolic control. While the minimal model index of insulin sensitivity, SI, has been used in studies of T1D, it has not before been evaluated against gold-...
Grg3/TLE3 and Grg1/TLE1 induce monohormonal pancreatic β-cells while repressing α-cell functions.
Diabetes 63(5):1804 (2014)
In the pancreas, α- and β-cells possess a degree of plasticity. In vitro differentiation of pluripotent cells yields mostly α- and polyhormonal β-like cells, indicating a gap in understanding of how functional monohormonal β-cells are formed and of the endogenous repressive mechanisms used to ma...