Relationship Between Insulin Secretion and Insulin Sensitivity and its Role in Development of Type 2 Diabetes Mellitus: Beyond the Disposition Index

Relationship Between Insulin Secretion and Insulin Sensitivity and its Role in Development of Type 2 Diabetes Mellitus: Beyond the Disposition Index james freeman diabetes freedom We assessed whether the relationship between insulin secretion and sensitivity predicted development of type 2 Read more

Active Brown Adipose Tissue is Associated With a Healthier Metabolic Phenotype in Obesity

Active Brown Adipose Tissue is Associated With a Healthier Metabolic Phenotype in Obesity james freeman diabetes freedom Obesity is associated with increasing cardiometabolic morbidity and mortality worldwide. Not everyone with obesity, however, develops metabolic complications. Brown adipose tissue (BAT) has Read more

Novel Human Insulin Isoforms and C{alpha}-peptide Product in Islets of Langerhans and Choroid Plexus

Novel Human Insulin Isoforms and C{alpha}-peptide Product in Islets of Langerhans and Choroid Plexus james freeman diabetes freedom Human insulin (INS) gene diverged from the ancestral genes of invertebrate and mammalian species millions of years ago. We previously found that Read more

Empagliflozin Treatment is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes

Empagliflozin Treatment is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes james freeman diabetes freedom Sodium—glucose-cotransporter-2 (SGLT2) inhibitors reduce the risk of major adverse CV events and hospitalization Read more

Reduced Follicular Regulatory T Cells in Spleen and Pancreatic Lymph Nodes of Patients With Type 1 Diabetes

Reduced Follicular Regulatory T Cells in Spleen and Pancreatic Lymph Nodes of Patients With Type 1 Diabetes james freeman diabetes freedom In the attempt to understand the origin of autoantibody (AAb) production in patients with and at-risk for T1D, multiple Read more

Increased Energy Expenditure and Protection from Diet-Induced Obesity in Mice Lacking the cGMP-Specific Phosphodiesterase PDE9

Increased Energy Expenditure and Protection from Diet-Induced Obesity in Mice Lacking the cGMP-Specific Phosphodiesterase PDE9 james freeman diabetes freedom Cyclic nucleotides, cAMP and cGMP, are important second messengers for the regulation of adaptive thermogenesis. Their levels are controlled not only Read more

Possible Involvement of Adipose Tissue in Older and Obese Diabetic Patients with Coronavirus SARS-CoV-2 Infection (COVID-19) via GRP78 (BIP/HSPA5): Significance of Hyperinsulinemia Management in COVID-19

Possible Involvement of Adipose Tissue in Older and Obese Diabetic Patients with Coronavirus SARS-CoV-2 Infection (COVID-19) via GRP78 (BIP/HSPA5): Significance of Hyperinsulinemia Management in COVID-19 james freeman diabetes freedom Aging, obesity and diabetes are major risk factors for the severe Read more

The Tetracycline-Controlled Transactivator (Tet-On/Off) System in Beta Cells Reduces Insulin Expression and Secretion in Mice

The Tetracycline-Controlled Transactivator (Tet-On/Off) System in Beta Cells Reduces Insulin Expression and Secretion in Mice james freeman diabetes freedom Controllable genetic manipulation is an indispensable tool in research, greatly advancing our understanding of cell biology and physiology. However in beta Read more

Genetic Studies of Metabolomics Change After a Liquid Meal Illuminate Novel Pathways for Glucose and Lipid Metabolism

Genetic Studies of Metabolomics Change After a Liquid Meal Illuminate Novel Pathways for Glucose and Lipid Metabolism james freeman diabetes freedom Humans spend the greater part of the day in a postprandial state. However, the genetic basis of postprandial blood Read more

Empagliflozin Treatment is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes

Empagliflozin Treatment is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes james freeman diabetes freedom Sodium—glucose-cotransporter-2 (SGLT2) inhibitors reduce the risk of major adverse CV events and hospitalization Read more

Diabetes, Drug Treatment and Mortality in COVID-19: A Multinational Retrospective Cohort Study

Diabetes, Drug Treatment and Mortality in COVID-19: A Multinational Retrospective Cohort Study james freeman diabetes freedom Patients with type 2 diabetes mellitus (T2DM) are at increased risk of severe COVID-19 outcomes possibly due to dysregulated inflammatory responses. Glucose-regulating medications such Read more

Imeglimin ameliorates {beta}-cell apoptosis by modulating the endoplasmic reticulum homeostasis pathway

Imeglimin ameliorates {beta}-cell apoptosis by modulating the endoplasmic reticulum homeostasis pathway james freeman diabetes freedom The effects of imeglimin, a novel anti-diabetes agent, on β-cell function remain unclear. Here, we unveiled the impact of imeglimin on β-cell survival. Treatment with Read more

Diabetes, Drug Treatment and Mortality in COVID-19: A Multinational Retrospective Cohort Study

Diabetes, Drug Treatment and Mortality in COVID-19: A Multinational Retrospective Cohort Study james freeman diabetes freedom Patients with type 2 diabetes mellitus (T2DM) are at increased risk of severe COVID-19 outcomes possibly due to dysregulated inflammatory responses. Glucose-regulating medications such Read more

CD8+ T cells variably recognize native versus citrullinated GRP78 epitopes in type 1 diabetes

CD8+ T cells variably recognize native versus citrullinated GRP78 epitopes in type 1 diabetes james freeman diabetes freedom In type 1 diabetes, autoimmune β-cell destruction may be favored by neo-antigens harboring post-translational modifications such as citrullination. We studied the recognition Read more

CD8+ T cells variably recognize native versus citrullinatedGRP78 epitopes in type 1 diabetes

CD8+ T cells variably recognize native versus citrullinatedGRP78 epitopes in type 1 diabetes james freeman diabetes freedom In type 1 diabetes, autoimmune β-cell destruction may be favored by neo-antigens harboring post-translational modifications such as citrullination. We studied the recognition of Read more

Contraction-Mediated Glucose Transport in Skeletal Muscle is Regulated by a Framework of AMPK, TBC1D1/4 and Rac1

Contraction-Mediated Glucose Transport in Skeletal Muscle is Regulated by a Framework of AMPK, TBC1D1/4 and Rac1 james freeman diabetes freedom The two closely related RabGTPase-activating proteins (RabGAPs) TBC1D1 and TBC1D4, both substrates for the AMP-activated protein kinase AMPK, play important Read more

Syntaxin 4 enrichment in {beta}-cells prevents conversion to autoimmune diabetes in non-obese diabetic (NOD) mice

Syntaxin 4 enrichment in {beta}-cells prevents conversion to autoimmune diabetes in non-obese diabetic (NOD) mice james freeman diabetes freedom Syntaxin 4 (STX4), a plasma membrane-localized SNARE protein, regulates human islet β-cell insulin secretion and preservation of β-cell mass. We found Read more

Gene Panel Sequencing of Patients With Monogenic Diabetes Brings to Light Genes Typically Associated With Syndromic Presentations

Gene Panel Sequencing of Patients With Monogenic Diabetes Brings to Light Genes Typically Associated With Syndromic Presentations james freeman diabetes freedom Gene panel sequencing (NGS) offers the possibility to analyze rare forms of monogenic diabetes (MgD). To that end, 18 Read more

Developmental Timing of High Fat Diet Exposure Impacts Glucose Homeostasis in Mice in a Sex-Specific Manner

Developmental Timing of High Fat Diet Exposure Impacts Glucose Homeostasis in Mice in a Sex-Specific Manner james freeman diabetes freedom We previously demonstrated that male, but not female, Swiss Webster mice are susceptible to diabetes, with incidence increased by early Read more

The Deterrence of Rapid Metabolic Decline within 3 Months after Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes

The Deterrence of Rapid Metabolic Decline within 3 Months after Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes james freeman diabetes freedom Endpoints that provide an early identification of treatment effects are needed to implement type 1 Read more

Developmental Timing of High Fat Diet Exposure Impacts Glucose Homeostasis in Mice in a Sex-Specific Manner

Developmental Timing of High Fat Diet Exposure Impacts Glucose Homeostasis in Mice in a Sex-Specific Manner james freeman diabetes freedom We previously demonstrated that male, but not female, Swiss Webster mice are susceptible to diabetes, with incidence increased by early Read more

Different effects of lifestyle intervention in high- and low-risk prediabetes

Different effects of lifestyle intervention in high- and low-risk prediabetes james freeman diabetes freedom Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested if prediabetic individuals with low risk benefit Read more

Activation of HIF1{alpha} Rescues the Hypoxic Response and Reverses Metabolic Dysfunction in the Diabetic Heart

Activation of HIF1{alpha} Rescues the Hypoxic Response and Reverses Metabolic Dysfunction in the Diabetic Heart james freeman diabetes freedom Type 2 diabetes (T2D) impairs Hypoxia-Inducible Factor (HIF)1α activation, a master transcription factor that drives cellular adaptation to hypoxia. Reduced activation Read more

Spatial Regulation of Reactive Oxygen Species via G6PD in Brown Adipocytes Supports Thermogenic Function

Spatial Regulation of Reactive Oxygen Species via G6PD in Brown Adipocytes Supports Thermogenic Function james freeman diabetes freedom Reactive oxygen species (ROS) are associated with various roles of brown adipocytes. Glucose-6-phosphate dehydrogenase (G6PD) controls cellular redox potentials by producing NADPH. Read more

Coxsackievirus B Vaccines Prevent Infection-Accelerated Diabetes in NOD Mice and Have No Disease-Inducing Effect

Coxsackievirus B Vaccines Prevent Infection-Accelerated Diabetes in NOD Mice and Have No Disease-Inducing Effect james freeman diabetes freedom Enteroviruses, including the Coxsackievirus Bs (CVB), have been implicated as causal agents in human type 1 diabetes. Immunization of at-risk individuals with Read more

Chromogranin A Deficiency Confers Protection from Autoimmune Diabetes Via Multiple Mechanisms

Chromogranin A Deficiency Confers Protection from Autoimmune Diabetes Via Multiple Mechanisms james freeman diabetes freedom Recognition of beta-cell antigens by autoreactive T cells is a critical step in the initiation of autoimmune Type1 diabetes (T1D). A complete protection from diabetes Read more

Hepatocytic Activating Transcription Factor 3 Protects Against Steatohepatitis Via Hepatocyte Nuclear Factor 4{alpha}

Hepatocytic Activating Transcription Factor 3 Protects Against Steatohepatitis Via Hepatocyte Nuclear Factor 4{alpha} james freeman diabetes freedom Activating transcription factor 3 (ATF3) has been shown to play an important role in HDL metabolism, yet the role of hepatocytic ATF3 in Read more

Effect of Systemic Hypertension on Peripapillary RNFL Thickness in Diabetic Patients Without Diabetic Retinopathy

Effect of Systemic Hypertension on Peripapillary RNFL Thickness in Diabetic Patients Without Diabetic Retinopathy james freeman diabetes freedom Type 2 diabetes (T2DM) and hypertension (HTN) are both relatively common systemic diseases and cause damage to the retina, such as inner Read more

{beta}-Cell Knockout of SENP1 Reduces Responses to Incretins and Worsens Oral Glucose Tolerance in High Fat Diet-Fed Mice

{beta}-Cell Knockout of SENP1 Reduces Responses to Incretins and Worsens Oral Glucose Tolerance in High Fat Diet-Fed Mice james freeman diabetes freedom SUMOylation reduces oxidative stress and preserves islet mass at the expense of robust insulin secretion. To investigate a Read more

OGT Regulates Mitochondrial Biogenesis and Function via Diabetes Susceptibility Gene Pdx1

OGT Regulates Mitochondrial Biogenesis and Function via Diabetes Susceptibility Gene Pdx1 james freeman diabetes freedom O-GlcNAc transferase (OGT), a nutrient-sensor sensitive to glucose flux, is highly expressed in the pancreas. However, the role of OGT in the mitochondria of β-cells Read more

Predisposition to Proinsulin Misfolding as a Genetic Risk to Diet-Induced Diabetes

Predisposition to Proinsulin Misfolding as a Genetic Risk to Diet-Induced Diabetes james freeman diabetes freedom Throughout evolution, proinsulin has exhibited significant sequence variation in both C-peptide and insulin moieties. As the proinsulin coding sequence evolves, the gene product continues to Read more

Leukocyte Counts and T Cell Frequencies Differ Between Novel Subgroups of Diabetes and Associate with Metabolic Parameters and Biomarkers of Inflammation

Leukocyte Counts and T Cell Frequencies Differ Between Novel Subgroups of Diabetes and Associate with Metabolic Parameters and Biomarkers of Inflammation james freeman diabetes freedom Frequencies of circulating immune cells are altered in type 1 and type 2 diabetes compared Read more

Lipid Droplets Protect Human {beta} Cells from Lipotoxic-Induced Stress and Cell Identity Changes

Lipid Droplets Protect Human {beta} Cells from Lipotoxic-Induced Stress and Cell Identity Changes james freeman diabetes freedom Free fatty acids (FFAs) are often stored in lipid droplet (LD) depots for eventual metabolic and/or synthetic use in many cell types, such Read more

Sleeve Gastrectomy Suppresses Hepatic Glucose Production and Increases Hepatic Insulin Clearance Independent of Weight Loss

Sleeve Gastrectomy Suppresses Hepatic Glucose Production and Increases Hepatic Insulin Clearance Independent of Weight Loss james freeman diabetes freedom Bariatric operations induce weight loss, which is associated with an improvement in hepatic steatosis and a reduction in hepatic glucose production. Read more

LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes

LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes james freeman diabetes freedom Diabetes is a known risk factor for severe coronavirus disease 2019 (COVID-19), the disease caused by the new coronavirus severe acute respiratory Read more