Tag Archives: {beta}Cell

Apoptosis Repressor With Caspase Recruitment Domain Ameliorates Amyloid-Induced {beta}-Cell Apoptosis and JNK Pathway Activation

Islet amyloid is present in more than 90% of individuals with type 2 diabetes, where it contributes to β-cell apoptosis and insufficient insulin secretion. Apoptosis repressor with caspase recruitment domain (ARC) binds and inactivates components of the intrinsic and extrinsic apoptosis pathways and was recently found to be expressed in islet β-cells. Using a human islet amyloid polypeptide transgenic mouse model of islet amyloidosis, we show ARC knockdown increases amyloid-induced β-cell apoptosis and loss, while ARC overexpression decreases amyloid-induced apoptosis, thus preserving β-cells. These effects occurred in the absence of changes in islet amyloid deposition, indicating ARC acts downstream of amyloid formation. Because islet amyloid increases c-Jun N-terminal kinase (JNK) pathway activation, we investigated whether ARC affects JNK signaling in amyloid-forming islets. We found ARC knockdown enhances JNK pathway activation, whereas ARC overexpression reduces JNK, c-Jun phosphorylation, and c-Jun target gene expression (Jun and Tnf). Immunoprecipitation of ARC from mouse islet lysates showed ARC binds JNK, suggesting interaction between JNK and ARC decreases amyloid-induced JNK phosphorylation and downstream signaling. These data indicate that ARC overexpression diminishes amyloid-induced JNK pathway activation and apoptosis in the β-cell, a strategy that may reduce β-cell loss in type 2 diabetes.

Diabetes Journal current issue





  • Twitter
  • del.icio.us
  • Digg
  • Facebook
  • Technorati
  • Reddit
  • Yahoo Buzz
  • StumbleUpon

Impact of Changes Over Time in Adipokines and Inflammatory Proteins on Changes in Insulin Sensitivity, {beta}-Cell Function, and Glycemia in Women With Previous Gestational Dysglycemia

Ravi Retnakaran
Aug 1, 2017; 40:e101-e102
e-Letters: Observations
: Most-Read Full-Text Articles





  • Twitter
  • del.icio.us
  • Digg
  • Facebook
  • Technorati
  • Reddit
  • Yahoo Buzz
  • StumbleUpon

Response to Comment on Rodriguez-Calvo et al. Increase in Pancreatic Proinsulin and Preservation of {beta}-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset. Diabetes 2017;66:1334-1345

Diabetes Journal current issue





  • Twitter
  • del.icio.us
  • Digg
  • Facebook
  • Technorati
  • Reddit
  • Yahoo Buzz
  • StumbleUpon

Comment on Rodriguez-Calvo et al. Increase in Pancreatic Proinsulin and Preservation of {beta}-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset. Diabetes 2017;66:1334-1345

Diabetes Journal current issue





  • Twitter
  • del.icio.us
  • Digg
  • Facebook
  • Technorati
  • Reddit
  • Yahoo Buzz
  • StumbleUpon

Pair Feeding, but Not Insulin, Phloridzin, or Rosiglitazone Treatment, Curtails Markers of {beta}-Cell Dedifferentiation in db/db Mice

β-Cell failure is a hallmark of type 2 diabetes. Among several cellular biological mechanisms of cellular dysfunction, we and others have recently proposed that dedifferentiation of β-cells can explain the slowly progressive onset and partial reversibility of β-cell failure. Accordingly, we provided evidence of such processes in humans and experimental animal models of insulin-resistant diabetes. In this study, we asked whether β-cell dedifferentiation can be prevented with diet or pharmacological treatment of diabetes. db/db mice, a widely used model of insulin-resistant diabetes and obesity, were either pair fed or treated with the Sglt inhibitor phloridzin, the insulin-sensitizer rosiglitazone, or insulin. All treatments were equally efficacious in reducing plasma glucose levels. Pair feeding and phloridzin also resulted in significant weight loss. However, pair feeding among the four treatments resulted in a reduction of β-cell dedifferentiation, as assessed by Foxo1 and Aldh1a3 immunohistochemistry. The effect of diet to partly restore β-cell function is consistent with data in human diabetes and provides another potential mechanism by which lifestyle changes act as an effective intervention against diabetes progression.

Diabetes Journal current issue





  • Twitter
  • del.icio.us
  • Digg
  • Facebook
  • Technorati
  • Reddit
  • Yahoo Buzz
  • StumbleUpon

Bait and Trap: Enriching Autoreactive T Cells With {beta}-Cell Antigen-Loading Biomaterial Scaffolds for Early Detection of Type 1 Diabetes

Diabetes Journal current issue





  • Twitter
  • del.icio.us
  • Digg
  • Facebook
  • Technorati
  • Reddit
  • Yahoo Buzz
  • StumbleUpon

Longitudinal Associations Between Ambient Air Pollution With Insulin Sensitivity, {beta}-Cell Function, and Adiposity in Los Angeles Latino Children

Evidence suggests that ambient air pollution (AAP) exposure may contribute to the development of obesity and type 2 diabetes. The objective of this study was to determine whether exposure to elevated concentrations of nitrogen dioxide (NO2) and particulate matter with aerodynamic diameter <2.5 (PM2.5) had adverse effects on longitudinal measures of insulin sensitivity (SI), β-cell function, and obesity in children at high risk for developing diabetes. Overweight and obese Latino children (8–15 years; n = 314) were enrolled between 2001 and 2012 from Los Angeles, CA, and followed for an average of 3.4 years (SD 3.1 years). Linear mixed-effects models were fitted to assess relationships between AAP exposure and outcomes after adjusting for covariates including body fat percent. Higher NO2 and PM2.5 were associated with a faster decline in SI and a lower SI at age 18 years, independent of adiposity. NO2 exposure negatively affected β-cell function, evidenced by a faster decline in disposition index (DI) and a lower DI at age 18 years. Higher NO2 and PM2.5 exposures over follow-up were also associated with a higher BMI at age 18 years. AAP exposure may contribute to development of type 2 diabetes through direct effects on SI and β-cell function.

Diabetes Journal current issue





  • Twitter
  • del.icio.us
  • Digg
  • Facebook
  • Technorati
  • Reddit
  • Yahoo Buzz
  • StumbleUpon

Checks and Balances–The Limits of {beta}-Cell Endurance to ER Stress

Diabetes Journal current issue





  • Twitter
  • del.icio.us
  • Digg
  • Facebook
  • Technorati
  • Reddit
  • Yahoo Buzz
  • StumbleUpon

Adiponectin and {beta}-Cell Adaptation in Pregnancy

Diabetes Journal current issue





  • Twitter
  • del.icio.us
  • Digg
  • Facebook
  • Technorati
  • Reddit
  • Yahoo Buzz
  • StumbleUpon

Oxytocin Improves {beta}-Cell Responsivity and Glucose Tolerance in Healthy Men

In addition to its pivotal role in psychosocial behavior, the hypothalamic neuropeptide oxytocin contributes to metabolic control by suppressing eating behavior. Its involvement in glucose homeostasis is less clear, although pilot experiments suggest that oxytocin improves glucose homeostasis. We assessed the effect of intranasal oxytocin (24 IU) administered to 29 healthy, fasted male subjects on glucose homeostasis measured by means of an oral glucose tolerance test. Parameters of glucose metabolism were analyzed according to the oral minimal model. Oxytocin attenuated the peak excursion of plasma glucose and augmented the early increases in insulin and C-peptide concentrations in response to the glucose challenge, while slightly blunting insulin and C-peptide peaks. Oral minimal model analyses revealed that oxytocin compared with placebo induced a pronounced increase in β-cell responsivity (PHItotal) that was largely due to an enhanced dynamic response (PHId), and a more than twofold improvement in glucose tolerance (disposition index). Adrenocorticotropic hormone (ACTH), cortisol, glucagon, and nonesterified fatty acid (NEFA) concentrations were not or were only marginally affected. These results indicate that oxytocin plays a significant role in the acute regulation of glucose metabolism in healthy humans and render the oxytocin system a potential target of antidiabetic treatment.

Diabetes Journal current issue





  • Twitter
  • del.icio.us
  • Digg
  • Facebook
  • Technorati
  • Reddit
  • Yahoo Buzz
  • StumbleUpon