C. Bruce Verchere
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View article: Assessment of protein synthesis rate enables metabolic profiling of resident-immune cells of the islets of Langerhans
Assessment of protein synthesis rate enables metabolic profiling of resident-immune cells of the islets of Langerhans Open
Pancreatic islet-resident immune cells, such as lymphocytes and macrophages, support islet homeostasis, beta cell development, and tissue repair. In pathological states, including diabetes, islet immune cells can trigger inflammation, caus…
View article: α cells use both PC1/3 and PC2 to process proglucagon peptides and control insulin secretion
α cells use both PC1/3 and PC2 to process proglucagon peptides and control insulin secretion Open
α cells secrete proglucagon peptides to regulate nutrient metabolism. Recent findings support an α cell–to–β cell axis that is mediated by paracrine signaling through the glucagon receptor and glucagon-like peptide 1 (GLP-1) receptor in β …
View article: Human and mouse regenerative macrophages enhance beta cell survival, function, and proliferation
Human and mouse regenerative macrophages enhance beta cell survival, function, and proliferation Open
Aims/hypothesis Type 1 diabetes is an autoimmune disease caused by immune-mediated destruction of insulin-producing pancreatic beta cells. Interestingly, individuals with long-standing type 1 diabetes have residual beta cells, suggesting t…
View article: Localized GLP1 receptor pre-internalization directs pancreatic alpha cell to beta cell communication
Localized GLP1 receptor pre-internalization directs pancreatic alpha cell to beta cell communication Open
Pancreatic alpha cells modulate beta cell function in a paracrine manner through the release of glucagon. However, the detailed molecular architecture underlying alpha-to-beta cell regulation remains poorly characterized. Here, we show tha…
View article: Persisting plasma proinsulin levels in a cohort of 482 individuals with long‐standing type 1 diabetes mellitus
Persisting plasma proinsulin levels in a cohort of 482 individuals with long‐standing type 1 diabetes mellitus Open
Aims As compared with C‐peptide, plasma proinsulin levels in individuals with long‐standing type 1 diabetes mellitus are relatively understudied, but may serve as a marker of stressed, yet alive β‐cells. Materials and Methods We measured p…
View article: CCL22-expressing Stem Cell–derived Islet Grafts Recruit Regulatory T Cells in Mice
CCL22-expressing Stem Cell–derived Islet Grafts Recruit Regulatory T Cells in Mice Open
Background. Cell therapy using human donor or stem cell–derived islets (SC-islets) to replace lost insulin-producing beta (β) cells holds great promise for type 1 diabetes. Recruiting regulatory T cells (Treg) through chemokine signaling c…
View article: Elevations in plasma proinsulin predict the development of diabetes in NOD mice
Elevations in plasma proinsulin predict the development of diabetes in NOD mice Open
The global incidence of type 1 diabetes (T1D) continues to rise, yet reliable biomarkers for predicting disease onset remain limited. Studies have demonstrated persistent proinsulin secretion in individuals living with T1D, suggesting a pr…
View article: Cell therapy with human interleukin 10–producing ILC2s enhances islet function and inhibits allograft rejection
Cell therapy with human interleukin 10–producing ILC2s enhances islet function and inhibits allograft rejection Open
View article: Inhibition of xanthine oxidoreductase with febuxostat, but not allopurinol, prevents inflammasome assembly and IL-1β release
Inhibition of xanthine oxidoreductase with febuxostat, but not allopurinol, prevents inflammasome assembly and IL-1β release Open
Xanthine oxidoreductase (XOR) inhibitors are used to treat gout, inhibiting uric acid production, which causes clinical symptoms. Commonly used XOR inhibitors are the small molecule febuxostat (Fbx) and the purine analogue allopurinol (All…
View article: Peptidylglycine alpha-amidating monooxygenase is important in mice for beta-cell cilia formation and insulin secretion but promotes diabetes risk through beta-cell independent mechanisms
Peptidylglycine alpha-amidating monooxygenase is important in mice for beta-cell cilia formation and insulin secretion but promotes diabetes risk through beta-cell independent mechanisms Open
Eliminating Pam expression only in beta cells leads to morphological changes in insulin granules, reduced insulin secretion, reduced hIAPP amyloid burden and altered ciliogenesis. However, in mice beta-cell Pam deficiency has no impact on …
View article: Quantitative analysis of islet prohormone convertase 1/3 expression in human pancreas donors with diabetes
Quantitative analysis of islet prohormone convertase 1/3 expression in human pancreas donors with diabetes Open
Aims/hypothesis Islet prohormone-processing enzymes convert peptide hormone precursors to mature hormones. Defective beta cell prohormone processing and the release of incompletely processed peptide hormones are observed prior to the onset…
View article: An INSULIN and IAPP dual reporter enables tracking of functional maturation of stem cell-derived insulin producing cells
An INSULIN and IAPP dual reporter enables tracking of functional maturation of stem cell-derived insulin producing cells Open
The INS2A-EGFP/+;IAPP2A-mScarlet/+ hESC line provides a useful tool for tracking populations of maturing hESC-derived β cells in vitro. This tool has already been shared with 3 groups and is freely available to all.
View article: HumanIslets: An integrated platform for human islet data access and analysis
HumanIslets: An integrated platform for human islet data access and analysis Open
SUMMARY Comprehensive molecular and cellular phenotyping of human islets can enable deep mechanistic insights for diabetes research. We established the Human Islet Data Analysis and Sharing (HI-DAS) consortium to advance goals in accessibi…
View article: Top-Down Proteomics of Mouse Islets With Beta Cell CPE Deletion Reveals Molecular Details in Prohormone Processing
Top-Down Proteomics of Mouse Islets With Beta Cell CPE Deletion Reveals Molecular Details in Prohormone Processing Open
Altered prohormone processing, such as with proinsulin and pro-islet amyloid polypeptide (proIAPP), has been reported as an important feature of prediabetes and diabetes. Proinsulin processing includes removal of several C-terminal basic a…
View article: A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models
A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models Open
View article: Insulin B peptide-MHC class II-specific chimeric antigen receptor-Tregs prevent autoimmune diabetes in mice
Insulin B peptide-MHC class II-specific chimeric antigen receptor-Tregs prevent autoimmune diabetes in mice Open
Adoptive immunotherapy with Tregs is a promising approach for preventing or treating type 1 diabetes. Islet antigen-specific Tregs have more potent therapeutic effects than polyclonal cells, but their low frequency is a barrier for clinica…
View article: <strong>Residual β-cell function is associated with longer time in range in individuals with type 1 diabetes</strong>
<strong>Residual β-cell function is associated with longer time in range in individuals with type 1 diabetes</strong> Open
Objective. Little is known about the influence of residual islet function on glycemic control in type 1 diabetes (T1D). Therefore, we investigated the associations between residual β-cell function and metrics of continuo…
View article: <strong>Residual β-cell function is associated with longer time in range in individuals with type 1 diabetes</strong>
<strong>Residual β-cell function is associated with longer time in range in individuals with type 1 diabetes</strong> Open
Objective. Little is known about the influence of residual islet function on glycemic control in type 1 diabetes (T1D). Therefore, we investigated the associations between residual β-cell function and metrics of continuo…
View article: Residual β-Cell Function Is Associated With Longer Time in Range in Individuals With Type 1 Diabetes
Residual β-Cell Function Is Associated With Longer Time in Range in Individuals With Type 1 Diabetes Open
OBJECTIVE Little is known about the influence of residual islet function on glycemic control in type 1 diabetes (T1D). We investigated the associations between residual β-cell function and metrics of continuous glucose monitoring (CGM) in …
View article: <strong>Deletion of carboxypeptidase E in beta cells disrupts proinsulin processing but does not lead to spontaneous development of diabetes in mice</strong>
<strong>Deletion of carboxypeptidase E in beta cells disrupts proinsulin processing but does not lead to spontaneous development of diabetes in mice</strong> Open
Carboxypeptidase E (CPE) facilitates the conversion of prohormones into mature hormones and is highly expressed in multiple neuroendocrine tissues. Carriers of CPE mutations have elevated plasma proinsulin and develop severe obesi…
View article: <strong>Deletion of carboxypeptidase E in beta cells disrupts proinsulin processing but does not lead to spontaneous development of diabetes in mice</strong>
<strong>Deletion of carboxypeptidase E in beta cells disrupts proinsulin processing but does not lead to spontaneous development of diabetes in mice</strong> Open
Carboxypeptidase E (CPE) facilitates the conversion of prohormones into mature hormones and is highly expressed in multiple neuroendocrine tissues. Carriers of CPE mutations have elevated plasma proinsulin and develop severe obesi…
View article: Deletion of Carboxypeptidase E in β-Cells Disrupts Proinsulin Processing but Does Not Lead to Spontaneous Development of Diabetes in Mice
Deletion of Carboxypeptidase E in β-Cells Disrupts Proinsulin Processing but Does Not Lead to Spontaneous Development of Diabetes in Mice Open
Carboxypeptidase E (CPE) facilitates the conversion of prohormones into mature hormones and is highly expressed in multiple neuroendocrine tissues. Carriers of CPE mutations have elevated plasma proinsulin and develop severe obesity and hy…
View article: Inducing an oxidized redox-balance improves anti-tumor CD8<sup>+</sup>T cell function
Inducing an oxidized redox-balance improves anti-tumor CD8<sup>+</sup>T cell function Open
SUMMARY Cancer immunotherapy using antigen-specific CD8 + T cells depends on long-lasting anti-tumor function of the in vitro expanded T cells. T cell function is intricately linked to the activity of many metabolic pathways directly impac…
View article: Strategies for optimizing CITE-seq for human islets and other tissues
Strategies for optimizing CITE-seq for human islets and other tissues Open
Defining the immunological landscape of human tissue is an important area of research, but challenges include the impact of tissue disaggregation on cell phenotypes and the low abundance of immune cells in many tissues. Here, we describe m…
View article: Insulin B peptide-MHC class II-specific chimeric antigen receptor-Tregs prevent autoimmune diabetes
Insulin B peptide-MHC class II-specific chimeric antigen receptor-Tregs prevent autoimmune diabetes Open
Adoptive immunotherapy with Tregs is a promising approach for prevention or treatment of type 1 diabetes. Islet antigen-specific Tregs have more potent therapeutic effects than polyclonal cells, but their low frequency is a barrier for cli…
View article: A small molecule improves diabetes in mice expressing human islet amyloid polypeptide
A small molecule improves diabetes in mice expressing human islet amyloid polypeptide Open
In recent years, the number of studies on islet and beta cell autophagy have substantially increased due to growing interest in the role of autophagy in maintaining cellular homeostasis in diabetes. In type 2 diabetes, human islet amyloid …
View article: Islet amyloid polypeptide does not suppress pancreatic cancer
Islet amyloid polypeptide does not suppress pancreatic cancer Open
View article: Deletion of carboxypeptidase E in beta cells disrupts proinsulin processing and alters beta cell identity in mice
Deletion of carboxypeptidase E in beta cells disrupts proinsulin processing and alters beta cell identity in mice Open
Carboxypeptidase E (CPE) facilitates the conversion of prohormones into mature hormones and is highly expressed in multiple neuroendocrine tissues. Carriers of CPE mutations have elevated plasma proinsulin and develop severe obesity and hy…
View article: SORLA mediates endocytic uptake of proIAPP and protects against islet amyloid deposition
SORLA mediates endocytic uptake of proIAPP and protects against islet amyloid deposition Open
View article: Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction
Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction Open
Hyperglycemia and type 2 diabetes (T2D) are caused by failure of pancreatic beta cells. The role of the gut microbiota in T2D has been studied, but causal links remain enigmatic. Obese individuals with or without T2D were included from two…