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 1001

Publication Record

Connections

A compendium of G-protein-coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure.
Ceddia RP, Collins S
(2020) Clin Sci (Lond) 134: 473-512
MeSH Terms: Adipocytes, Adipose Tissue, Animals, Diabetes Mellitus, Type 2, Energy Metabolism, Humans, Lipolysis, Nucleotides, Cyclic, Receptors, G-Protein-Coupled, Signal Transduction
Show Abstract · Added March 26, 2020
With the ever-increasing burden of obesity and Type 2 diabetes, it is generally acknowledged that there remains a need for developing new therapeutics. One potential mechanism to combat obesity is to raise energy expenditure via increasing the amount of uncoupled respiration from the mitochondria-rich brown and beige adipocytes. With the recent appreciation of thermogenic adipocytes in humans, much effort is being made to elucidate the signaling pathways that regulate the browning of adipose tissue. In this review, we focus on the ligand-receptor signaling pathways that influence the cyclic nucleotides, cAMP and cGMP, in adipocytes. We chose to focus on G-protein-coupled receptor (GPCR), guanylyl cyclase and phosphodiesterase regulation of adipocytes because they are the targets of a large proportion of all currently available therapeutics. Furthermore, there is a large overlap in their signaling pathways, as signaling events that raise cAMP or cGMP generally increase adipocyte lipolysis and cause changes that are commonly referred to as browning: increasing mitochondrial biogenesis, uncoupling protein 1 (UCP1) expression and respiration.
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
0 Communities
2 Members
0 Resources
10 MeSH Terms
Roux-en-Y gastric bypass surgery improves hepatic glucose metabolism and reduces plasma kisspeptin levels in morbidly obese patients with type 2 diabetes.
Flynn CR, Albaugh VL, Tamboli RA, Gregory JM, Bosompem A, Sidani RM, Winnick JJ
(2020) Am J Physiol Gastrointest Liver Physiol 318: G370-G374
MeSH Terms: Adolescent, Adult, Anastomosis, Roux-en-Y, Blood Glucose, Diabetes Mellitus, Type 2, Female, Glucagon, Glucose, Humans, Insulin, Kisspeptins, Liver, Male, Middle Aged, Obesity, Morbid, Treatment Outcome, Young Adult
Show Abstract · Added November 12, 2019
Roux-en-Y gastric bypass surgery (RYGB) is known to improve whole-body glucose metabolism in patients with type 2 diabetes (T2D), although the mechanisms are not entirely clear and are likely multifactorial. The aim of this study was to assess fasting hepatic glucose metabolism and other markers of metabolic activity before and after RYGB in patients with and without T2D. Methods: Metabolic characteristics of patients who are obese with T2D were compared with those without the disease (non-T2D) before and 1 and 6 mo after RYGB. Fasting plasma insulin and the insulin:glucagon ratio were markedly reduced as early as 1 mo after RYGB in both patients with T2D and without T2D. Despite this reduction, endogenous glucose production and fasting plasma glucose levels were lower in both groups after RYGB, with the reductions being much larger in T2D. Plasma kisspeptin, an inhibitor of insulin secretion, was reduced only in T2D after surgery. Improved hepatic glucose metabolism and lower plasma kisspeptin in T2D after RYGB may link improved hepatic function with enhanced insulin responsiveness after surgery. Our manuscript is the first, to the best of our knowledge, to present data showing that Roux-en-Y gastric bypass surgery (RYGB) lowers fasting kisspeptin levels in patients who are obese with type 2 diabetes. This lowering of kisspeptin is important because it could link improvements in liver glucose metabolism after RYGB with increased insulin responsiveness also seen after surgery.
0 Communities
2 Members
0 Resources
17 MeSH Terms
Metabolic effects of skeletal muscle-specific deletion of beta-arrestin-1 and -2 in mice.
Meister J, Bone DBJ, Godlewski G, Liu Z, Lee RJ, Vishnivetskiy SA, Gurevich VV, Springer D, Kunos G, Wess J
(2019) PLoS Genet 15: e1008424
MeSH Terms: Animals, Diabetes Mellitus, Type 2, Diet, High-Fat, Disease Models, Animal, Glucose, Glucose Clamp Technique, Glycogen, Humans, Insulin, Insulin Resistance, Male, Mice, Mice, Knockout, Muscle, Skeletal, Obesity, Signal Transduction, beta-Arrestin 1, beta-Arrestin 2
Show Abstract · Added March 18, 2020
Type 2 diabetes (T2D) has become a major health problem worldwide. Skeletal muscle (SKM) is the key tissue for whole-body glucose disposal and utilization. New drugs aimed at improving insulin sensitivity of SKM would greatly expand available therapeutic options. β-arrestin-1 and -2 (Barr1 and Barr2, respectively) are two intracellular proteins best known for their ability to mediate the desensitization and internalization of G protein-coupled receptors (GPCRs). Recent studies suggest that Barr1 and Barr2 regulate several important metabolic functions including insulin release and hepatic glucose production. Since SKM expresses many GPCRs, including the metabolically important β2-adrenergic receptor, the goal of this study was to examine the potential roles of Barr1 and Barr2 in regulating SKM and whole-body glucose metabolism. Using SKM-specific knockout (KO) mouse lines, we showed that the loss of SKM Barr2, but not of SKM Barr1, resulted in mild improvements in glucose tolerance in diet-induced obese mice. SKM-specific Barr1- and Barr2-KO mice did not show any significant differences in exercise performance. However, lack of SKM Barr2 led to increased glycogen breakdown following a treadmill exercise challenge. Interestingly, mice that lacked both Barr1 and Barr2 in SKM showed no significant metabolic phenotypes. Thus, somewhat surprisingly, our data indicate that SKM β-arrestins play only rather subtle roles (SKM Barr2) in regulating whole-body glucose homeostasis and SKM insulin sensitivity.
0 Communities
1 Members
0 Resources
MeSH Terms
Metabolite Profiles of Incident Diabetes and Heterogeneity of Treatment Effect in the Diabetes Prevention Program.
Chen ZZ, Liu J, Morningstar J, Heckman-Stoddard BM, Lee CG, Dagogo-Jack S, Ferguson JF, Hamman RF, Knowler WC, Mather KJ, Perreault L, Florez JC, Wang TJ, Clish C, Temprosa M, Gerszten RE, Diabetes Prevention Program Research Group
(2019) Diabetes 68: 2337-2349
MeSH Terms: Adult, Aged, Biomarkers, Cytosine, Diabetes Mellitus, Type 2, Female, Humans, Incidence, Life Style, Male, Metabolome, Middle Aged, Risk Factors
Show Abstract · Added March 3, 2020
Novel biomarkers of type 2 diabetes (T2D) and response to preventative treatment in individuals with similar clinical risk may highlight metabolic pathways that are important in disease development. We profiled 331 metabolites in 2,015 baseline plasma samples from the Diabetes Prevention Program (DPP). Cox models were used to determine associations between metabolites and incident T2D, as well as whether associations differed by treatment group (i.e., lifestyle [ILS], metformin [MET], or placebo [PLA]), over an average of 3.2 years of follow-up. We found 69 metabolites associated with incident T2D regardless of treatment randomization. In particular, cytosine was novel and associated with the lowest risk. In an exploratory analysis, 35 baseline metabolite associations with incident T2D differed across the treatment groups. Stratification by baseline levels of several of these metabolites, including specific phospholipids and AMP, modified the effect that ILS or MET had on diabetes development. Our findings highlight novel markers of diabetes risk and preventative treatment effect in individuals who are clinically at high risk and motivate further studies to validate these interactions.
© 2019 by the American Diabetes Association.
0 Communities
1 Members
0 Resources
13 MeSH Terms
Long-term outcomes in mouse models of ischemia-reperfusion-induced acute kidney injury.
Scarfe L, Menshikh A, Newton E, Zhu Y, Delgado R, Finney C, de Caestecker MP
(2019) Am J Physiol Renal Physiol 317: F1068-F1080
MeSH Terms: Acute Kidney Injury, Animals, Diabetes Mellitus, Experimental, Diabetic Nephropathies, Disease Models, Animal, Female, Fibrosis, Kidney Function Tests, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred DBA, Nephrectomy, Reperfusion Injury, Sex Characteristics, Species Specificity
Show Abstract · Added May 10, 2020
Severe acute kidney injury has a high mortality and is a risk factor for progressive chronic kidney disease. None of the potential therapies that have been identified in preclinical studies have successfully improved clinical outcomes. This failure is partly because animal models rarely reflect the complexity of human disease: most preclinical studies are short term and are commonly performed in healthy, young, male mice. Therapies that are effective in preclinical models that share common clinical features seen in patients with acute kidney injury, including genetic diversity, different sexes, and comorbidities, and evaluate long-term outcomes are more likely to predict success in the clinic. Here, we evaluated susceptibility to chronic kidney disease after ischemia-reperfusion injury with delayed nephrectomy by monitoring long-term functional and histological responses to injury. We defined conditions required to induce long-term postinjury renal dysfunction and fibrosis without increased mortality in a reproducible way and evaluate effect of mouse strains, sexes, and preexisting diabetes on these responses.
0 Communities
1 Members
0 Resources
MeSH Terms
Plasma apoM and S1P levels are inversely associated with mortality in African Americans with type 2 diabetes mellitus.
Liu M, Frej C, Langefeld CD, Divers J, Bowden DW, Carr JJ, Gebre AK, Xu J, Larsson B, Dahlbäck B, Freedman BI, Parks JS
(2019) J Lipid Res 60: 1425-1431
MeSH Terms: African Americans, Apolipoproteins M, Biomarkers, Diabetes Mellitus, Type 2, Disease-Free Survival, Female, Humans, Lysophospholipids, Male, Middle Aged, Sphingosine, Survival Rate
Show Abstract · Added January 10, 2020
apoM is a minor HDL apolipoprotein and carrier for sphingosine-1-phosphate (S1P). HDL apoM and S1P concentrations are inversely associated with atherosclerosis progression in rodents. We evaluated associations between plasma concentrations of S1P, plasma concentrations of apoM, and HDL apoM levels with prevalent subclinical atherosclerosis and mortality in the African American-Diabetes Heart Study participants (N = 545). Associations between plasma S1P, plasma apoM, and HDL apoM with subclinical atherosclerosis and mortality were assessed using multivariate parametric, nonparametric, and Cox proportional hazards models. At baseline, participants' median (25th percentile, 75th percentile) age was 55 (49, 62) years old and their coronary artery calcium (CAC) mass score was 26.5 (0.0, 346.5). Plasma S1P, plasma apoM, and HDL apoM were not associated with CAC. After 64 (57.6, 70.3) months of follow-up, 81 deaths were recorded. Higher concentrations of plasma S1P [odds ratio (OR) = 0.14, = 0.01] and plasma apoM (OR = 0.10, = 0.02), but not HDL apoM ( = 0.89), were associated with lower mortality after adjusting for age, sex, statin use, CAC, kidney function, and albuminuria. We conclude that plasma S1P and apoM concentrations are inversely and independently associated with mortality, but not CAC, in African Americans with type 2 diabetes after accounting for conventional risk factors.
Copyright © 2019 Liu et al.
0 Communities
1 Members
0 Resources
12 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
Iatrogenic Hyperinsulinemia, Not Hyperglycemia, Drives Insulin Resistance in Type 1 Diabetes as Revealed by Comparison With GCK-MODY (MODY2).
Gregory JM, Smith TJ, Slaughter JC, Mason HR, Hughey CC, Smith MS, Kandasamy B, Greeley SAW, Philipson LH, Naylor RN, Letourneau LR, Abumrad NN, Cherrington AD, Moore DJ
(2019) Diabetes 68: 1565-1576
MeSH Terms: Adolescent, Adult, Diabetes Mellitus, Type 2, Female, Humans, Hyperglycemia, Hyperinsulinism, Insulin Resistance, Male, Middle Aged, Models, Theoretical, Young Adult
Show Abstract · Added May 17, 2019
Although insulin resistance consistently occurs with type 1 diabetes, its predominant driver is uncertain. We therefore determined the relative contributions of hyperglycemia and iatrogenic hyperinsulinemia to insulin resistance using hyperinsulinemic-euglycemic clamps in three participant groups ( = 10/group) with differing insulinemia and glycemia: healthy control subjects (euinsulinemia and euglycemia), glucokinase-maturity-onset diabetes of the young (GCK-MODY; euinsulinemia and hyperglycemia), and type 1 diabetes (hyperinsulinemia and hyperglycemia matching GCK-MODY). We assessed the contribution of hyperglycemia by comparing insulin sensitivity in control and GCK-MODY and the contribution of hyperinsulinemia by comparing GCK-MODY and type 1 diabetes. Hemoglobin A was normal in control subjects and similarly elevated for type 1 diabetes and GCK-MODY. Basal insulin levels in control subjects and GCK-MODY were nearly equal but were 2.5-fold higher in type 1 diabetes. Low-dose insulin infusion suppressed endogenous glucose production similarly in all groups and suppressed nonesterified fatty acids similarly between control subjects and GCK-MODY, but to a lesser extent for type 1 diabetes. High-dose insulin infusion stimulated glucose disposal similarly in control subjects and GCK-MODY but was 29% and 22% less effective in type 1 diabetes, respectively. Multivariable linear regression showed that insulinemia-but not glycemia-was significantly associated with muscle insulin sensitivity. These data suggest that iatrogenic hyperinsulinemia predominates in driving insulin resistance in type 1 diabetes.
© 2019 by the American Diabetes Association.
0 Communities
2 Members
0 Resources
12 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
GLP-1: Molecular mechanisms and outcomes of a complex signaling system.
Smith NK, Hackett TA, Galli A, Flynn CR
(2019) Neurochem Int 128: 94-105
MeSH Terms: Animals, Brain, Diabetes Mellitus, Type 2, Feeding Behavior, Glucagon-Like Peptide 1, Humans, Obesity, Reward, Signal Transduction
Show Abstract · Added December 17, 2019
Meal ingestion provokes the release of hormones and transmitters, which in turn regulate energy homeostasis and feeding behavior. One such hormone, glucagon-like peptide-1 (GLP-1), has received significant attention in the treatment of obesity and diabetes due to its potent incretin effect. In addition to the peripheral actions of GLP-1, this hormone is able to alter behavior through the modulation of multiple neural circuits. Recent work that focused on elucidating the mechanisms and outcomes of GLP-1 neuromodulation led to the discovery of an impressive array of GLP-1 actions. Here, we summarize the many levels at which the GLP-1 signal adapts to different systems, with the goal being to provide a background against which to guide future research.
Copyright © 2019. Published by Elsevier Ltd.
0 Communities
2 Members
0 Resources
9 MeSH Terms