Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 221

Publication Record

Connections

Peripherally delivered hepatopreferential insulin analog insulin-406 mimics the hypoglycaemia-sparing effect of portal vein human insulin infusion in dogs.
Gregory JM, Kraft G, Scott MF, Neal DW, Farmer B, Smith MS, Hastings JR, Madsen P, Kjeldsen TB, Hostrup S, Brand CL, Fledelius C, Nishimura E, Cherrington AD
(2019) Diabetes Obes Metab 21: 2294-2304
MeSH Terms: Animals, Blood Glucose, Diabetes Mellitus, Type 1, Dogs, Gluconeogenesis, Humans, Hypoglycemia, Hypoglycemic Agents, Infusions, Intravenous, Insulin, Insulin, Regular, Human, Liver, Male, Portal Vein
Show Abstract · Added June 26, 2019
AIMS - We previously quantified the hypoglycaemia-sparing effect of portal vs peripheral human insulin delivery. The current investigation aimed to determine whether a bioequivalent peripheral vein infusion of a hepatopreferential insulin analog, insulin-406, could similarly protect against hypoglycaemia.
MATERIALS AND METHODS - Dogs received human insulin infusions into either the hepatic portal vein (PoHI, n = 7) or a peripheral vein (PeHI, n = 7) for 180 minutes at four-fold the basal secretion rate (6.6 pmol/kg/min) in a previous study. Insulin-406 (Pe406, n = 7) was peripherally infused at 6.0 pmol/kg/min, a rate determined to decrease plasma glucose by the same amount as with PoHI infusion during the first 60 minutes. Glucagon was fixed at basal concentrations, mimicking the diminished α-cell response seen in type 1 diabetes.
RESULTS - Glucose dropped quickly with PeHI infusion, reaching 41 ± 3 mg/dL at 60 minutes, but more slowly with PoHI and Pe406 infusion (67 ± 2 and 72 ± 4 mg/dL, respectively; P < 0.01 vs PeHI for both). The hypoglycaemic nadir (c. 40 mg/dL) occurred at 60 minutes with PeHI infusion vs 120 minutes with PoHI and Pe406 infusion. ΔAUC during the 180-minute insulin infusion period was two-fold higher with PeHI infusion compared with PoHI and Pe406 infusion. Glucose production (mg/kg/min) was least suppressed with PeHI infusion (Δ = 0.79 ± 0.33) and equally suppressed with PoHI and Pe406 infusion (Δ = 1.16 ± 0.21 and 1.18 ± 0.17, respectively; P = NS). Peak glucose utilization (mg/kg/min) was highest with PeHI infusion (4.94 ± 0.17) and less with PoHI and Pe406 infusion (3.58 ± 0.58 and 3.26 ± 0.08, respectively; P < 0.05 vs Pe for both).
CONCLUSIONS - Peripheral infusion of hepatopreferential insulin can achieve a metabolic profile that closely mimics portal insulin delivery, which reduces the risk of hypoglycaemia compared with peripheral insulin infusion.
© 2019 John Wiley & Sons Ltd.
0 Communities
1 Members
0 Resources
14 MeSH Terms
Regulation of Diabetogenic Immunity by IL-15-Activated Regulatory CD8 T Cells in Type 1 Diabetes.
Stocks BT, Wilson CS, Marshall AF, Hoopes EM, Moore DJ
(2019) J Immunol 203: 158-166
MeSH Terms: Adoptive Transfer, Animals, B-Lymphocytes, CD8 Antigens, Cells, Cultured, Diabetes Mellitus, Type 1, Disease Models, Animal, Humans, Immunotherapy, Adoptive, Interleukin-15, Macrophages, Mice, Mice, Inbred NOD, NK Cell Lectin-Like Receptor Subfamily A, T-Lymphocytes, Regulatory
Show Abstract · Added May 28, 2019
Unchecked collaboration between islet-reactive T and B lymphocytes drives type 1 diabetes (T1D). In the healthy setting, CD8 T regulatory cells (Tregs) terminate ongoing T-B interactions. We determined that specific CD8 Tregs from NOD mice lack suppressive function, representing a previously unreported regulatory cell deficit in this T1D-prone strain. NOD mice possess 11-fold fewer Ly-49 CD8 Tregs than nonautoimmune mice, a deficiency that worsens as NOD mice age toward diabetes and leaves them unable to regulate CD4 T follicular helper cells. As IL-15 is required for Ly-49 CD8 Treg development, we determined that NOD macrophages inadequately -present IL-15. Despite reduced IL-15 -presentation, NOD Ly-49 CD8 Tregs can effectively transduce IL-15-mediated survival signals when they are provided. Following stimulation with an IL-15/IL-15Ra superagonist complex, Ly-49 CD8 Tregs expanded robustly and became activated to suppress the Ag-specific Ab response. IL-15/IL-15Ra superagonist complex-activated CD8CD122 T cells also delayed diabetes transfer, indicating the presence of an underactivated CD8 T cell subset with regulatory capacity against late stage T1D. We identify a new cellular contribution to anti-islet autoimmunity and demonstrate the correction of this regulatory cell deficit. Infusion of IL-15-activated CD8 Tregs may serve as an innovative cellular therapy for the treatment of T1D.
Copyright © 2019 by The American Association of Immunologists, Inc.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Medical and Psychological Considerations for Carbohydrate-Restricted Diets in Youth With Type 1 Diabetes.
Gallagher KAS, DeSalvo D, Gregory J, Hilliard ME
(2019) Curr Diab Rep 19: 27
MeSH Terms: Adolescent, Blood Glucose, Child, Depression, Diabetes Mellitus, Type 1, Diet, Carbohydrate-Restricted, Feeding and Eating Disorders, Humans
Show Abstract · Added June 26, 2019
PURPOSE OF REVIEW - Given the challenges achieving recommended glycemic targets in youth with type 1 diabetes (T1D), providers may consider recommending carbohydrate-restricted diets (CRDs) to optimize glycemic control. The goal of the present review is to describe relevant literature on the potential medical and psychosocial benefits and risks of CRDs in youth with T1D.
RECENT FINDINGS - Limited data exist on the effects of CRDs in pediatric populations. Findings from studies with youth and adults are mixed; some indicate that CRDs may be associated with desirable medical outcomes, such as improved glycemic control and reduced HbA1c, which may contribute to positive psychological outcomes such as reduced diabetes distress and depressive symptoms. Others suggest that CRDs may also be associated with detrimental outcomes, including mineral deficiencies and suboptimal growth, and dietary restriction has been linked to greater diabetes distress, disordered eating, and diabetes management. More research is needed to evaluate benefits and risks of CRDs in youth. Providers should exercise caution when discussing CRDs with youth and families, particularly when considering CRDs for youth at elevated risk for eating disordered behavior.
0 Communities
1 Members
0 Resources
8 MeSH Terms
B lymphocytes protect islet β cells in diabetes prone NOD mice treated with imatinib.
Wilson CS, Spaeth JM, Karp J, Stocks BT, Hoopes EM, Stein RW, Moore DJ
(2019) JCI Insight 5:
MeSH Terms: Animals, Autoimmunity, B-Lymphocytes, Cell Proliferation, Diabetes Mellitus, Type 1, Disease Models, Animal, Homeodomain Proteins, Hyperglycemia, Imatinib Mesylate, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Maf Transcription Factors, Large, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Knockout
Show Abstract · Added April 10, 2019
Imatinib (Gleevec) reverses type 1 diabetes (T1D) in NOD mice and is currently in clinical trials in individuals with recent-onset disease. While research has demonstrated that imatinib protects islet β cells from the harmful effects of ER stress, the role the immune system plays in its reversal of T1D has been less well understood, and specific cellular immune targets have not been identified. In this study, we demonstrate that B lymphocytes, an immune subset that normally drives diabetes pathology, are unexpectedly required for reversal of hyperglycemia in NOD mice treated with imatinib. In the presence of B lymphocytes, reversal was linked to an increase in serum insulin concentration, but not an increase in islet β cell mass or proliferation. However, improved β cell function was reflected by a partial recovery of MafA transcription factor expression, a sensitive marker of islet β cell stress that is important to adult β cell function. Imatinib treatment was found to increase the antioxidant capacity of B lymphocytes, improving reactive oxygen species (ROS) handling in NOD islets. This study reveals a novel mechanism through which imatinib enables B lymphocytes to orchestrate functional recovery of T1D β cells.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Pancreas Volume Declines During the First Year After Diagnosis of Type 1 Diabetes and Exhibits Altered Diffusion at Disease Onset.
Virostko J, Williams J, Hilmes M, Bowman C, Wright JJ, Du L, Kang H, Russell WE, Powers AC, Moore DJ
(2019) Diabetes Care 42: 248-257
MeSH Terms: Adolescent, Adult, Atrophy, Autoantibodies, Case-Control Studies, Child, Child, Preschool, Cohort Studies, Diabetes Mellitus, Type 1, Female, Glucose Tolerance Test, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Pancreas, Time Factors, Young Adult
Show Abstract · Added December 18, 2018
OBJECTIVE - This study investigated the temporal dynamics of pancreas volume and microstructure in children and adolescents with recent-onset type 1 diabetes (T1D) and individuals without diabetes, including a subset expressing autoantibodies associated with the early stages of T1D.
RESEARCH DESIGN AND METHODS - MRI was performed in individuals with recent-onset stage 3 T1D ( = 51; median age 13 years) within 100 days after diagnosis (mean 67 days), 6 months, and 1 year postdiagnosis. Longitudinal MRI measurements were also made in similarly aged control participants ( = 57) and in autoantibody-positive individuals without diabetes ( = 20). The MRI protocol consisted of anatomical imaging to determine pancreas volume and quantitative MRI protocols interrogating tissue microstructure and composition.
RESULTS - Within 100 days of diabetes onset, individuals with T1D had a smaller pancreas (median volume 28.6 mL) than control participants (median volume 48.4 mL; < 0.001), including when normalized by individual weight ( < 0.001). Longitudinal measurements of pancreas volume increased in control participants over the year, consistent with adolescent growth, but pancreas volume declined over the first year after T1D diagnosis ( < 0.001). In multiple autoantibody-positive individuals, the pancreas volume was significantly larger than that of the T1D cohort ( = 0.017) but smaller than that of the control cohort ( = 0.04). Diffusion-weighted MRI showed that individuals with recent-onset T1D had a higher apparent diffusion coefficient ( = 0.012), suggesting a loss of cellular structural integrity, with heterogeneous pancreatic distribution.
CONCLUSIONS - These results indicate that pancreas volume is decreased in stages 1, 2, and 3 of T1D and decreases during the first year after diabetes onset and that this loss of pancreatic volume is accompanied by microstructural changes.
© 2018 by the American Diabetes Association.
1 Communities
4 Members
0 Resources
19 MeSH Terms
Human islets expressing HNF1A variant have defective β cell transcriptional regulatory networks.
Haliyur R, Tong X, Sanyoura M, Shrestha S, Lindner J, Saunders DC, Aramandla R, Poffenberger G, Redick SD, Bottino R, Prasad N, Levy SE, Blind RD, Harlan DM, Philipson LH, Stein RW, Brissova M, Powers AC
(2019) J Clin Invest 129: 246-251
MeSH Terms: Adolescent, Adult, Diabetes Mellitus, Type 1, Genetic Variation, Hepatocyte Nuclear Factor 1-alpha, Heterozygote, Humans, Insulin-Secreting Cells, Male, Transcription, Genetic
Show Abstract · Added December 7, 2018
Using an integrated approach to characterize the pancreatic tissue and isolated islets from a 33-year-old with 17 years of type 1 diabetes (T1D), we found that donor islets contained β cells without insulitis and lacked glucose-stimulated insulin secretion despite a normal insulin response to cAMP-evoked stimulation. With these unexpected findings for T1D, we sequenced the donor DNA and found a pathogenic heterozygous variant in the gene encoding hepatocyte nuclear factor-1α (HNF1A). In one of the first studies of human pancreatic islets with a disease-causing HNF1A variant associated with the most common form of monogenic diabetes, we found that HNF1A dysfunction leads to insulin-insufficient diabetes reminiscent of T1D by impacting the regulatory processes critical for glucose-stimulated insulin secretion and suggest a rationale for a therapeutic alternative to current treatment.
0 Communities
4 Members
0 Resources
10 MeSH Terms
Ectonucleoside Triphosphate Diphosphohydrolase-3 Antibody Targets Adult Human Pancreatic β Cells for In Vitro and In Vivo Analysis.
Saunders DC, Brissova M, Phillips N, Shrestha S, Walker JT, Aramandla R, Poffenberger G, Flaherty DK, Weller KP, Pelletier J, Cooper T, Goff MT, Virostko J, Shostak A, Dean ED, Greiner DL, Shultz LD, Prasad N, Levy SE, Carnahan RH, Dai C, Sévigny J, Powers AC
(2019) Cell Metab 29: 745-754.e4
MeSH Terms: Adenosine Triphosphatases, Adult, Animals, Biomarkers, Cells, Cultured, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Insulin-Secreting Cells, Islets of Langerhans, Male, Membrane Proteins, Mice, Mice, Inbred NOD, Pancreas, Young Adult
Show Abstract · Added February 4, 2019
Identification of cell-surface markers specific to human pancreatic β cells would allow in vivo analysis and imaging. Here we introduce a biomarker, ectonucleoside triphosphate diphosphohydrolase-3 (NTPDase3), that is expressed on the cell surface of essentially all adult human β cells, including those from individuals with type 1 or type 2 diabetes. NTPDase3 is expressed dynamically during postnatal human pancreas development, appearing first in acinar cells at birth, but several months later its expression declines in acinar cells while concurrently emerging in islet β cells. Given its specificity and membrane localization, we utilized an NTPDase3 antibody for purification of live human β cells as confirmed by transcriptional profiling, and, in addition, for in vivo imaging of transplanted human β cells. Thus, NTPDase3 is a cell-surface biomarker of adult human β cells, and the antibody directed to this protein should be a useful new reagent for β cell sorting, in vivo imaging, and targeting.
Copyright © 2018 Elsevier Inc. All rights reserved.
0 Communities
3 Members
0 Resources
16 MeSH Terms
Sleep in Teens With Type 1 Diabetes: Perspectives From Adolescents and Their Caregivers.
Bergner EM, Williams R, Hamburger ER, Lyttle M, Davis AC, Malow B, Simmons JH, Lybarger C, Capin R, Jaser SS
(2018) Diabetes Educ 44: 541-548
MeSH Terms: Adolescent, Caregivers, Diabetes Mellitus, Type 1, Female, Humans, Male, Perception, Qualitative Research, Sleep, Sleep Wake Disorders
Show Abstract · Added January 30, 2019
PURPOSE - The purpose of this study is to identify barriers, facilitators, and consequences of obtaining sufficient sleep in adolescents with type 1 diabetes.
METHODS - Semistructured interviews were conducted with 25 adolescents (52% female, mean age = 15.6 years) and 25 caregivers. Interviews were transcribed and coded using Atlas.ti. A thematic analytic approach was used to identify and organize significant patterns of meaning (themes) and interpret themes across the data.
RESULTS - Several barriers were identified, with the most common being the use of electronics before bed and sleep disturbances related to diabetes management. Caregivers described strategies for helping adolescents achieve sufficient sleep, such as enforcing bedtimes and limiting distractions, but many adolescents could not identify facilitators of sleep. Weekday/weekend discrepancies in sleep timing were commonly disclosed.
CONCLUSIONS - This study is the first to examine the perceptions of barriers and facilitators to obtaining sufficient sleep in adolescents with T1D and their caregivers. Results have the potential to inform providers' recommendations regarding sleep, including possible interventions to promote sleep in this high-risk population.
0 Communities
2 Members
0 Resources
10 MeSH Terms
Healthy Donor Polyclonal IgMs Diminish B-Lymphocyte Autoreactivity, Enhance Regulatory T-Cell Generation, and Reverse Type 1 Diabetes in NOD Mice.
Wilson CS, Chhabra P, Marshall AF, Morr CV, Stocks BT, Hoopes EM, Bonami RH, Poffenberger G, Brayman KL, Moore DJ
(2018) Diabetes 67: 2349-2360
MeSH Terms: Animals, B-Lymphocytes, Diabetes Mellitus, Type 1, Immunoglobulin M, Mice, Mice, Inbred NOD, T-Lymphocytes, Regulatory
Show Abstract · Added August 23, 2018
Autoimmune diseases such as type 1 diabetes (T1D) arise from unrestrained activation of effector lymphocytes that destroy target tissues. Many efforts have been made to eliminate these effector lymphocytes, but none has produced a long-term cure. An alternative to depletion therapy is to enhance endogenous immune regulation. Among these endogenous alternatives, naturally occurring Igs have been applied for inflammatory disorders but have lacked potency in antigen-specific autoimmunity. We hypothesized that naturally occurring polyclonal IgMs, which represent the majority of circulating, noninduced antibodies but are present only in low levels in therapeutic Ig preparations, possess the most potent capacity to restore immune homeostasis. Treatment of diabetes-prone NOD mice with purified IgM isolated from Swiss Webster (SW) mice (nIgM) reversed new-onset diabetes, eliminated autoreactive B lymphocytes, and enhanced regulatory T-cell (Treg) numbers both centrally and peripherally. Conversely, IgM from prediabetic NOD mice could not restore this endogenous regulation, which represents an unrecognized component of T1D pathogenesis. Of note, IgM derived from healthy human donors was similarly able to expand human CD4 Tregs in humanized mice and produced permanent diabetes protection in treated NOD mice. Overall, these studies demonstrate that a potent, endogenous regulatory mechanism, nIgM, is a promising option for reversing autoimmune T1D in humans.
© 2018 by the American Diabetes Association.
0 Communities
2 Members
0 Resources
7 MeSH Terms
Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes.
Triolo TM, Fouts A, Pyle L, Yu L, Gottlieb PA, Steck AK, Type 1 Diabetes TrialNet Study Group
(2019) Diabetes Care 42: 192-199
MeSH Terms: Adolescent, Adult, Autoantibodies, Autoimmunity, Child, Child, Preschool, Diabetes Mellitus, Type 1, Disease Progression, Diseases in Twins, Environment, Female, Genetic Predisposition to Disease, Glutamate Decarboxylase, Humans, Insulin, Islets of Langerhans, Male, Mass Screening, Risk Factors, Seroepidemiologic Studies, Siblings, Twins, Twins, Dizygotic, Twins, Monozygotic, Young Adult
Show Abstract · Added August 15, 2018
OBJECTIVE - There are variable reports of risk of concordance for progression to islet autoantibodies and type 1 diabetes in identical twins after one twin is diagnosed. We examined development of positive autoantibodies and type 1 diabetes and the effects of genetic factors and common environment on autoantibody positivity in identical twins, nonidentical twins, and full siblings.
RESEARCH DESIGN AND METHODS - Subjects from the TrialNet Pathway to Prevention Study ( = 48,026) were screened from 2004 to 2015 for islet autoantibodies (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A], and autoantibodies against insulin [IAA]). Of these subjects, 17,226 (157 identical twins, 283 nonidentical twins, and 16,786 full siblings) were followed for autoantibody positivity or type 1 diabetes for a median of 2.1 years.
RESULTS - At screening, identical twins were more likely to have positive GADA, IA-2A, and IAA than nonidentical twins or full siblings (all < 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more positive autoantibodies, and two or more positive autoantibodies (all ≤ 0.03). Initially autoantibody-positive identical twins had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody-negative identical twins. In nonidentical twins, type 1 diabetes risk by 3 years was 72% for initially multiple autoantibody-positive, 13% for single autoantibody-positive, and 0% for initially autoantibody-negative nonidentical twins. Full siblings had a 3-year type 1 diabetes risk of 47% for multiple autoantibody-positive, 12% for single autoantibody-positive, and 0.5% for initially autoantibody-negative subjects.
CONCLUSIONS - Risk of type 1 diabetes at 3 years is high for initially multiple and single autoantibody-positive identical twins and multiple autoantibody-positive nonidentical twins. Genetic predisposition, age, and male sex are significant risk factors for development of positive autoantibodies in twins.
© 2018 by the American Diabetes Association.
0 Communities
2 Members
0 Resources
25 MeSH Terms