Gordon C. Weir
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View article: Renalase inhibition defends against acute and chronic β cell stress by regulating cell metabolism
Renalase inhibition defends against acute and chronic β cell stress by regulating cell metabolism Open
Our work illustrates a role for Rnls in regulating cell metabolism. We show that inhibiting Rnls protects against chronic stress in vivo, and shields against acute stress in β cell lines in vitro by rewiring cell metabolism towards glycoly…
View article: Renalase inhibition regulates β cell metabolism to defend against acute and chronic stress
Renalase inhibition regulates β cell metabolism to defend against acute and chronic stress Open
Renalase (Rnls), annotated as an oxidase enzyme, is a GWAS gene associated with Type 1 Diabetes (T1D) risk. We previously discovered that Rnls inhibition delays diabetes onset in mouse models of T1D in vivo , and protects pancreatic β cell…
View article: Enhancement of Subcutaneous Islet Transplant Performance by Collagen 1 Gel
Enhancement of Subcutaneous Islet Transplant Performance by Collagen 1 Gel Open
Human islets can be transplanted into the portal vein for T1 diabetes, and a similar procedure is being used in a clinical trial for stem cell–derived beta-like cells. Efforts have been underway to find an alternative transplant site that …
View article: Conflicting Views About Interactions Between Pancreatic α-Cells and β-Cells
Conflicting Views About Interactions Between Pancreatic α-Cells and β-Cells Open
In type 1 diabetes, the reduced glucagon response to insulin-induced hypoglycemia has been used to argue that β-cell secretion of insulin is required for the full glucagon counterregulatory response. For years, the concept has been that in…
View article: Induction of remission in diabetes by lowering blood glucose
Induction of remission in diabetes by lowering blood glucose Open
As diabetes continues to grow as major health problem, there has been great progress in understanding the important role of pancreatic beta-cells in its pathogenesis. Diabetes develops when the normal interplay between insulin secretion an…
View article: Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response
Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response Open
Biomedical devices comprise a major component of modern medicine, however immune-mediated fibrosis and rejection can limit their function over time. Here, we describe a humanized mouse model that recapitulates fibrosis following biomateria…
View article: Islet Inflammation Can Be Linked to the Disruption of Proinsulin Processing in Type 1 Diabetes but not in Type 2 Diabetes
Islet Inflammation Can Be Linked to the Disruption of Proinsulin Processing in Type 1 Diabetes but not in Type 2 Diabetes Open
Journal Article Islet Inflammation Can Be Linked to the Disruption of Proinsulin Processing in Type 1 Diabetes but not in Type 2 Diabetes Get access Gordon C Weir Gordon C Weir Joslin Diabetes Center, Harvard Medical School, Boston, MA 022…
View article: Reduced glucose-induced first-phase insulin release is a danger signal that predicts diabetes
Reduced glucose-induced first-phase insulin release is a danger signal that predicts diabetes Open
During progression to both types 1 and 2 diabetes (T1D, T2D), there is a striking loss of glucose-induced first-phase insulin release (FPIR), which is known to predict the onset of T1D. The contribution of reduced β cell mass to the onset …
View article: Why pancreatic islets should be regarded and regulated like organs.
Why pancreatic islets should be regarded and regulated like organs. Open
There are strong reasons to say that pancreatic islets are organs before they are isolated and that they should be considered to be organs once transplanted. Thus, taking into account how much we have learned about the structure and functi…
View article: Glucolipotoxicity, β-Cells, and Diabetes: The Emperor Has No Clothes
Glucolipotoxicity, β-Cells, and Diabetes: The Emperor Has No Clothes Open
Reduction of β-cell mass and function is central to the pathogenesis of type 2 diabetes. The terms glucotoxicity, lipotoxicity, and glucolipotoxicity are used to describe potentially responsible processes. The premise is that chronically e…
View article: SUN-LB059 A Rare Case Of Hypoglycemia Secondary To Proinsulin-Intermediate Secreting Tumor
SUN-LB059 A Rare Case Of Hypoglycemia Secondary To Proinsulin-Intermediate Secreting Tumor Open
IntroductionPancreatic neuroendocrine tumors (PNETs) that solely produce proinsulin (PI) manifesting with hypoglycemia and normal or low serum insulin (IN) levels are rare. Des 64-65 is a PI intermediate. We report a novel case of hypoglyc…
View article: Apolipoprotein E is a pancreatic extracellular factor that maintains mature β-cell gene expression
Apolipoprotein E is a pancreatic extracellular factor that maintains mature β-cell gene expression Open
The in vivo microenvironment of tissues provides myriad unique signals to cells. Thus, following isolation, many cell types change in culture, often preserving some but not all of their in vivo characteristics in culture. At least some of …
View article: Mixed Meal and Intravenous L-Arginine Tests Both Stimulate Incretin Release Across Glucose Tolerance in Man: Lack of Correlation with β Cell Function
Mixed Meal and Intravenous L-Arginine Tests Both Stimulate Incretin Release Across Glucose Tolerance in Man: Lack of Correlation with β Cell Function Open
Both MMTT and AST resulted in insulin and enteroendocrine hormone responses across GT populations without consistent correlation between release of incretins and insulin, which is in line with other published research. If a defect is in th…
View article: Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply
Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply Open
Transplantation of encapsulated islets can cure diabetes without immunosuppression, but oxygen supply limitations can cause failure. We investigated a retrievable macroencapsulation device wherein islets are encapsulated in a planar algina…
View article: Alpha-1 antitrypsin treatment of new-onset type 1 diabetes: An open-label, phase I clinical trial (RETAIN) to assess safety and pharmacokinetics
Alpha-1 antitrypsin treatment of new-onset type 1 diabetes: An open-label, phase I clinical trial (RETAIN) to assess safety and pharmacokinetics Open
The drug Alpha-1 Antitrypsin (AAT, Aralast NP) is being tested in this study as an anti-inflammatory drug (a medication that decreases inflammation, which is part of the body's normal ability to fight infection and respond to injuries) tha…
View article: Evidence of stress in <b>β</b> cells obtained with laser capture microdissection from pancreases of brain dead donors
Evidence of stress in <b>β</b> cells obtained with laser capture microdissection from pancreases of brain dead donors Open
Isolated islets used for transplantation are known to be stressed, which can result from the circumstances of death, in particular brain death, the preservation of the pancreas with its warm and cold ischemia, from the trauma of the isolat…
View article: Glucose Driven Changes in Beta Cell Identity Are Important for Function and Possibly Autoimmune Vulnerability during the Progression of Type 1 Diabetes
Glucose Driven Changes in Beta Cell Identity Are Important for Function and Possibly Autoimmune Vulnerability during the Progression of Type 1 Diabetes Open
This commentary explores the hypothesis that when autoimmunity leads to a fall of beta cell mass during the progression of type 1 diabetes (T1D), rising glucose levels cause major changes in beta cell identity. This then leads to profound …