Megan E. Capozzi
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View article: β Cell Gαs signaling is critical for physiological and pharmacological enhancement of insulin secretion
β Cell Gαs signaling is critical for physiological and pharmacological enhancement of insulin secretion Open
The incretin peptides glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors coordinate β cell secretion that is proportional to nutrient intake. This effect permits consistent and restricted glucose excursions …
View article: Ectopic, hepatic GLP-1R agonism enhances the weight loss efficacy of GLP-1 analogues
Ectopic, hepatic GLP-1R agonism enhances the weight loss efficacy of GLP-1 analogues Open
Objective Unimolecular triagonists drive substantial weight loss in patients with obesity (PwO) by engaging the glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) receptors to reduce food intake (FI) and…
View article: Development of a succinyl CoA:3-ketoacid CoA transferase inhibitor selective for peripheral tissues that improves glycemia in obesity
Development of a succinyl CoA:3-ketoacid CoA transferase inhibitor selective for peripheral tissues that improves glycemia in obesity Open
Many individuals with type 2 diabetes (T2D) cannot take current therapies due to their adverse effects. Thus, new glucose-lowering agents targeting unique mechanisms are needed. Studies have demonstrated that decreasing ketone oxidation, s…
View article: Induction, amplification, and propagation of diabetic retinopathy-associated inflammatory cytokines between human retinal microvascular endothelial and Müller cells and in the mouse retina
Induction, amplification, and propagation of diabetic retinopathy-associated inflammatory cytokines between human retinal microvascular endothelial and Müller cells and in the mouse retina Open
View article: Pancreas-derived DPP4 is not essential for glucose homeostasis under metabolic stress
Pancreas-derived DPP4 is not essential for glucose homeostasis under metabolic stress Open
Mice systemically lacking dipeptidyl peptidase-4 (DPP4) have improved islet health, glucoregulation, and reduced obesity with high-fat diet (HFD) feeding compared to wild-type mice. Some, but not all, of this improvement can be linked to t…
View article: The ubiquitination status of the glucagon receptor determines signal bias
The ubiquitination status of the glucagon receptor determines signal bias Open
View article: Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis
Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis Open
View article: The past, present, and future physiology and pharmacology of glucagon
The past, present, and future physiology and pharmacology of glucagon Open
View article: GLP-1-mediated delivery of tesaglitazar improves obesity and glucose metabolism in male mice
GLP-1-mediated delivery of tesaglitazar improves obesity and glucose metabolism in male mice Open
View article: Author Correction: Cytochrome P450-epoxygenated fatty acids inhibit Müller glial inflammation
Author Correction: Cytochrome P450-epoxygenated fatty acids inhibit Müller glial inflammation Open
View article: Nuclear factor of activated T-cells (NFAT) regulation of IL-1β-induced retinal vascular inflammation
Nuclear factor of activated T-cells (NFAT) regulation of IL-1β-induced retinal vascular inflammation Open
View article: Cytochrome P450-epoxygenated fatty acids inhibit Müller glial inflammation
Cytochrome P450-epoxygenated fatty acids inhibit Müller glial inflammation Open
Free fatty acid dysregulation in diabetics may elicit the release of inflammatory cytokines from Müller cells (MC), promoting the onset and progression of diabetic retinopathy (DR). Palmitic acid (PA) is elevated in the sera of diabetics a…
View article: GIP mediates the incretin effect and glucose tolerance by dual actions on α cells and β cells
GIP mediates the incretin effect and glucose tolerance by dual actions on α cells and β cells Open
GIPR activity in α cells is required for the complete metabolic response to a meal.
View article: Cytochrome P450-Epoxygenated Fatty Acids Inhibit Müller Glial Inflammation
Cytochrome P450-Epoxygenated Fatty Acids Inhibit Müller Glial Inflammation Open
BackgroundMüller cell (MC) inflammation is an early pathogenic step in the vision-threatening disease diabetic retinopathy (DR). Recent evidence indicates that diabetes-induced free fatty acid (FFA) dysregulation can elicit the release of …
View article: Pyruvate Kinase Controls Signal Strength in the Insulin Secretory Pathway
Pyruvate Kinase Controls Signal Strength in the Insulin Secretory Pathway Open
9 - Regulation of Glucose Metabolism via the Intra-Islet DPP4/Incretin Axis Open
View article: Repositioning the Alpha Cell in Postprandial Metabolism
Repositioning the Alpha Cell in Postprandial Metabolism Open
Glucose homeostasis is maintained in large part due to the actions of the pancreatic islet hormones insulin and glucagon, secreted from β- and α-cells, respectively. The historical narrative positions these hormones in opposition, with ins…
View article: Sustained release of a GLP-1 and FGF21 dual agonist from an injectable depot protects mice from obesity and hyperglycemia
Sustained release of a GLP-1 and FGF21 dual agonist from an injectable depot protects mice from obesity and hyperglycemia Open
A type 2 diabetes therapeutic merges two complementary drugs with a depot-forming linker to enable once-weekly dosing.
View article: Could micro changes in β-cells enable major changes in metabolism?
Could micro changes in β-cells enable major changes in metabolism? Open
View article: Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist
Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist Open
Tirzepatide (LY3298176) is a dual GIP and GLP-1 receptor agonist under development for the treatment of type 2 diabetes mellitus (T2DM), obesity, and nonalcoholic steatohepatitis. Early phase trials in T2DM indicate that tirzepatide improv…
View article: Discordance between GLP-1R gene and protein expression in mouse pancreatic islet cells
Discordance between GLP-1R gene and protein expression in mouse pancreatic islet cells Open
View article: Pimozide Alleviates Hyperglycemia in Diet-Induced Obesity by Inhibiting Skeletal Muscle Ketone Oxidation
Pimozide Alleviates Hyperglycemia in Diet-Induced Obesity by Inhibiting Skeletal Muscle Ketone Oxidation Open
View article: The Limited Role of Glucagon for Ketogenesis During Fasting or in Response to SGLT2 Inhibition
The Limited Role of Glucagon for Ketogenesis During Fasting or in Response to SGLT2 Inhibition Open
Glucagon is classically described as a counterregulatory hormone that plays an essential role in the protection against hypoglycemia. In addition to its role in the regulation of glucose metabolism, glucagon has been described to promote k…
View article: Pyruvate kinase controls signal strength in the insulin secretory pathway
Pyruvate kinase controls signal strength in the insulin secretory pathway Open
SUMMARY Pancreatic β-cells couple nutrient metabolism with appropriate insulin secretion. Here, we show that pyruvate kinase (PK), which converts ADP and phosphoenolpyruvate (PEP) into ATP and pyruvate, underlies β-cell sensing of both gly…
View article: Pyruvate Kinase Controls Signal Strength in the Insulin Secretory Pathway
Pyruvate Kinase Controls Signal Strength in the Insulin Secretory Pathway Open
View article: Pharmacological antagonism of the incretin system protects against diet-induced obesity
Pharmacological antagonism of the incretin system protects against diet-induced obesity Open
View article: The peroxisome proliferator-activated receptor-β/δ antagonist GSK0660 mitigates retinal cell inflammation and leukostasis
The peroxisome proliferator-activated receptor-β/δ antagonist GSK0660 mitigates retinal cell inflammation and leukostasis Open
View article: Glucagon lowers glycemia when β cells are active
Glucagon lowers glycemia when β cells are active Open
Glucagon and insulin are commonly believed to have counteracting effects on blood glucose levels. However, recent studies have demonstrated that glucagon has a physiologic role to activate β-cells and enhance insulin secretion. To date, th…
View article: Repositioning Glucagon Action in the Physiology and Pharmacology of Diabetes
Repositioning Glucagon Action in the Physiology and Pharmacology of Diabetes Open
Glucagon is historically described as the counterregulatory hormone to insulin, induced by fasting/hypoglycemia to raise blood glucose through action mediated in the liver. However, it is becoming clear that the biology of glucagon is much…
View article: β Cell tone is defined by proglucagon peptides through cAMP signaling
β Cell tone is defined by proglucagon peptides through cAMP signaling Open
Paracrine interactions between pancreatic islet cells have been proposed as a mechanism to regulate hormone secretion and glucose homeostasis. Here, we demonstrate the importance of proglucagon-derived peptides (PGDPs) for α to β cell comm…