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View article: Altered immune and metabolic molecular pathways drive islet cell dysfunction in human type 1 diabetes
Altered immune and metabolic molecular pathways drive islet cell dysfunction in human type 1 diabetes Open
Type 1 diabetes (T1D) is characterized by the autoimmune destruction of most insulin-producing β cells, along with dysregulated glucagon secretion from pancreatic α cells. We conducted an integrated analysis that combines electrophysiologi…
View article: TMEM55A-mediated PI5P signalling regulates alpha cell actin depolymerisation and glucagon secretion
TMEM55A-mediated PI5P signalling regulates alpha cell actin depolymerisation and glucagon secretion Open
We reveal a novel pathway by which TMEM55A regulates alpha cell exocytosis by controlling intracellular PI5P and the F-actin network.
View article: TMEM55A-mediated PI5P signaling regulates α-cell actin depolymerization and glucagon secretion
TMEM55A-mediated PI5P signaling regulates α-cell actin depolymerization and glucagon secretion Open
Diabetes is associated with the dysfunction of glucagon-producing pancreatic islet α-cells, although the underlying mechanisms regulating glucagon secretion and α-cell dysfunction remain unclear. While insulin secretion from pancreatic β-c…
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: Retrospective Evaluation of a Pragmatic Deprescribing Initiative in a Skilled Nursing Facility System
Retrospective Evaluation of a Pragmatic Deprescribing Initiative in a Skilled Nursing Facility System Open
CONTEXT: Polypharmacy increases risk of adverse drug effects. OBJECTIVE: To retrospectively determine whether a pragmatic deprescribing protocol reduced 8 common classes of medications in two skilled nursing facilities (SNFs) in a single s…
View article: Zmiz1 is required for mature β-cell function and mass expansion upon high fat feeding
Zmiz1 is required for mature β-cell function and mass expansion upon high fat feeding Open
Genome-wide association studies have identified hundreds of signals for type 2 diabetes (T2D), most of which confer risk through effects on gene expression. We previously identified the transcription factor ZMIZ1 as a probable effector tra…
View article: β-cell responses to high fat feeding: A role and mechanism for redox sensing by SENP1
β-cell responses to high fat feeding: A role and mechanism for redox sensing by SENP1 Open
Pancreatic β-cells respond to metabolic stress by upregulating insulin secretion, however the underlying mechanisms remain unclear. In β-cells from overweight humans without diabetes, and mice fed a high-fat diet for 2 days, insulin exocyt…
View article: Impacts of the COVID-19 pandemic on a human research islet program
Impacts of the COVID-19 pandemic on a human research islet program Open
Designated a pandemic in March 2020, the spread of severe acute respiratory syndrome virus 2 (SARS-CoV2), the virus responsible for coronavirus disease 2019 (COVID-19), led to new guidelines and restrictions being implemented for individua…
View article: Impacts of the COVID-19 Pandemic on a Human Research Islet Program
Impacts of the COVID-19 Pandemic on a Human Research Islet Program Open
Designated a pandemic in March 2020, the spread of severe acute respiratory syndrome virus 2 (SARS-CoV2), the virus responsible for coronavirus disease 2019 (COVID-19), led to new guidelines and restrictions being implemented for individua…
View article: Impaired mRNA Based COVID-19 Vaccine Response in Patients with B-Cell Malignancies after CD19 Directed CAR-T Cell Therapy
Impaired mRNA Based COVID-19 Vaccine Response in Patients with B-Cell Malignancies after CD19 Directed CAR-T Cell Therapy Open
Introduction: Patients with hematologic malignancies are at an increased risk of morbidity and mortality from COVID-19 disease (Vijenthira, Blood 2020). This is likely a result of combination of immunodeficiency conferred by the disease an…
View article: β-Cell Knockout of SENP1 Reduces Responses to Incretins and Worsens Oral Glucose Tolerance in High-Fat Diet–Fed Mice
β-Cell Knockout of SENP1 Reduces Responses to Incretins and Worsens Oral Glucose Tolerance in High-Fat Diet–Fed Mice Open
SUMOylation reduces oxidative stress and preserves islet mass at the expense of robust insulin secretion. To investigate a role for the deSUMOylating enzyme sentrin-specific protease 1 (SENP1) following metabolic stress, we put pancreas/gu…
View article: Isolation of Human Pancreatic Islets of Langerhans for Research v3
Isolation of Human Pancreatic Islets of Langerhans for Research v3 Open
This protocol, and the five linked protocols, describe the equipment setup, solutions, and methodology for the isolation of pancreatic islets of Langerhans from human donor pancreas for research purposes. These protocols are employed by th…
View article: Heterogenous impairment of α-cell function in type 2 diabetes is linked to cell maturation state
Heterogenous impairment of α-cell function in type 2 diabetes is linked to cell maturation state Open
In diabetes, glucagon secretion from pancreatic α-cells is dysregulated. We examined α-cells from human donors and mice using combined electrophysiological, transcriptomic, and computational approaches. Rising glucose suppresses α-cell exo…
View article: β-cell SENP1 facilitates responsiveness to incretins and limits oral glucose intolerance in high fat fed mice
β-cell SENP1 facilitates responsiveness to incretins and limits oral glucose intolerance in high fat fed mice Open
SUMOylation reduces oxidative stress and preserves islet mass; but this happens at the expense of robust insulin secretion. To investigate a role for the deSUMOylating enzyme sen trin-specific p rotease 1 (SENP1) in glycemia following meta…
View article: Improved glucose tolerance with DPPIV inhibition requires β‐cell SENP1 amplification of glucose‐stimulated insulin secretion
Improved glucose tolerance with DPPIV inhibition requires β‐cell SENP1 amplification of glucose‐stimulated insulin secretion Open
Pancreatic islet insulin secretion is amplified by both metabolic and receptor-mediated signaling pathways. The incretin-mimetic and DPPIV inhibitor anti-diabetic drugs increase insulin secretion, but in humans this can be variable both in…
View article: A role for PKD1 in insulin secretion downstream of P2Y <sub>1</sub> receptor activation in mouse and human islets
A role for PKD1 in insulin secretion downstream of P2Y <sub>1</sub> receptor activation in mouse and human islets Open
Along with insulin, β-cells co-secrete the neurotransmitter ATP which acts as a positive autocrine signal via P2Y1 receptors to activate phospholipase C and increase the production of diacylglycerol (DAG). However, the downstream signaling…
View article: Isolation of Human Pancreatic Islets of Langerhans for Research v2
Isolation of Human Pancreatic Islets of Langerhans for Research v2 Open
This protocol, and the five linked protocols, describe the equipment setup, solutions, and methodology for the isolation of pancreatic islets of Langerhans from human donor pancreas for research purposes. These protocols are employed by th…
View article: IP Glucose Tolerance Test in Mouse v1
IP Glucose Tolerance Test in Mouse v1 Open
This protocol details the IP glucose tolerance test in mice. This is performed on C57Bl6, transgenic SENP1 KO and ZMIZ1 KO mouse models. Typically GTT's are done at 12 weeks of age. Following the GTT on chow diet, some mice are put on high…
View article: Insulin Tolerance Test in Mouse v1
Insulin Tolerance Test in Mouse v1 Open
This protocol details the insulin tolerance test in mice. This is performed on C57Bl6, transgenic SENP1 KO and ZMIZ1 KO mouse models. Typically glucose tolerance tests (GTTs) are performed at 12 weeks of age, followed by an ITT 2 weeks lat…
View article: Purification of Mouse Pancreatic Islets using Histopaque Gradient Centrifugation v1
Purification of Mouse Pancreatic Islets using Histopaque Gradient Centrifugation v1 Open
This protocol details the purification of mouse pancreatic islets using histopaque gradient centrifugation.
View article: Oral Glucose Tolerance Test in Mouse v1
Oral Glucose Tolerance Test in Mouse v1 Open
This protocol details the oral glucose tolerance test in mice. This is performed on C57Bl6, transgenic SENP1 KO and ZMIZ1 KO mouse models. Typically GTT's are done at 12 weeks of age. Following the GTT on chow diet, some mice are put on hi…
View article: Mouse Pancreatic Islet Isolation v1
Mouse Pancreatic Islet Isolation v1 Open
This protocol details islet isolation from mouse pancreas. The protocol is divided into 3 main parts; in situ perfusion of pancreas with collagenase, pancreas digestion, and islet purification. A link is provided for the purification using…
View article: SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells
SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human ß cells Open
Insulin secretion from pancreatic ß cells is a multistep process that requires the coordination of exocytotic proteins that integrate diverse signals. These include signals derived from metabolic control of post-translational SUMOylation a…
View article: Association Between Weight Change, Clinical Outcomes, and Health Care Costs in Patients with Type 2 Diabetes
Association Between Weight Change, Clinical Outcomes, and Health Care Costs in Patients with Type 2 Diabetes Open
This study was sponsored by AstraZeneca and Bristol-Myers Squibb. Truven Health Analytics received funding from Bristol-Myers Squibb and AstraZeneca to conduct this study. Mukherjee is an employee of Bristol-Myers Squibb. Bell and Sternhuf…
View article: Interleukin-1 signaling contributes to acute islet compensation
Interleukin-1 signaling contributes to acute islet compensation Open
IL-1β is a well-established inducer of both insulin resistance and impaired pancreatic islet function. Despite this, findings examining IL-1 receptor deficiency or antagonism in in vivo animal models, as well as in clinical studies of type…