A5035893164- Pancreatic function and diabetes
- Diabetes Treatment and Management
- Diabetes and associated disorders
- Metabolism, Diabetes, and Cancer
- Diet and metabolism studies
- Receptor Mechanisms and Signaling
- Diet, Metabolism, and Disease
- Neuropeptides and Animal Physiology
- Chemical Synthesis and Analysis
- Sleep and Wakefulness Research
- Amino Acid Enzymes and Metabolism
- Cancer, Hypoxia, and Metabolism
- Diabetes Management and Research
- Biochemical Analysis and Sensing Techniques
- Adipose Tissue and Metabolism
- Regulation of Appetite and Obesity
Duke University
2020-2024
Duke University Hospital
2020-2023
Duke Medical Center
2020-2023
Indiana University School of Medicine
2020-2023
Indiana University – Purdue University Indianapolis
2020-2023
Indianapolis Zoo
2018
Abstract The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) mediate insulin responses that are proportionate to nutrient intake facilitate glucose tolerance . GLP-1 receptor (GLP-1R) is an established drug target for the treatment of diabetes obesity 2 , whereas therapeutic potential GIP (GIPR) a subject debate. Tirzepatide agonist at both GIPR GLP-1R highly effective type 3,4 However, although tirzepatide activates in cell lines mouse...
GIPR activity in α cells is required for the complete metabolic response to a meal.
Central glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) signaling is critical in GIP-based therapeutics’ ability to lower body weight, but pathways leveraged by GIPR pharmacology the brain remain incompletely understood. We explored role of Gipr neurons hypothalamus and dorsal vagal complex (DVC) — regions control energy balance. Hypothalamic expression was not necessary for synergistic effect GIPR/GLP-1R coagonism on weight. While chemogenetic stimulation both...
Glucagon is classically described as a counterregulatory hormone that plays an essential role in the protection against hypoglycemia. In addition to its regulation of glucose metabolism, glucagon has been promote ketosis fasted state. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are new class glucose-lowering drugs act primarily kidney, but some reports have direct effects SGLT2i on α-cells stimulate secretion. Interestingly, SGLT2 inhibition also results increased endogenous...
Glucose-dependent insulinotropic polypeptide (GIP) is one of the two major incretin factors that regulate metabolic homeostasis. Genetic ablation its receptor (GIPR) in mice confers protection against diet-induced obesity (DIO), while GIPR neutralizing antibodies produce additive weight reduction when combined with GLP-1R agonists preclinical models and clinical trials. Conversely, have been shown to promote loss rodents, dual GLP-1R/GIPR proven superior monoagonists for We sought develop a...
The insulinotropic actions of glucagon-like peptide 1 receptor (GLP-1R) in β-cells have made it a useful target to manage type 2 diabetes. Metabolic stress reduces β-cell sensitivity GLP-1, yet the underlying mechanisms are unknown. We hypothesized that Glp1r expression is heterogeneous among and metabolic decreases number GLP-1R-positive β-cells. Here, analyses publicly available single-cell RNA-Seq sequencing (scRNASeq) data from mouse human indicated significant populations do not express...
The pancreatic hormone glucagon activates the receptor (GCGR), a class B seven-transmembrane G protein-coupled that couples to stimulatory heterotrimeric protein and provokes PKA-dependent signaling cascades vital hepatic glucose metabolism islet insulin secretion. Glucagon-stimulation also initiates recruitment of endocytic adaptors, βarrestin1 βarrestin2, which regulate desensitization internalization GCGR. Unlike many other receptors, GCGR expressed at plasma membrane is constitutively...
12-Lipoxygenase (12-LOX) is a key enzyme in arachidonic acid metabolism, and alongside its major product, 12-HETE, plays role promoting inflammatory signaling during diabetes pathogenesis. Although 12-LOX proposed therapeutic target to protect pancreatic islets the setting of diabetes, little known about consequences blocking enzymatic activity embryonic development. Here, we have leveraged strengths zebrafish—genetic manipulation pharmacologic inhibition—to interrogate Lipidomics analysis...
ABSTRACT Type 1 Diabetes (T1D) is caused by autoimmune-mediated beta cell destruction. Following injury, the pancreas attempts to launch a cellular repair and regenerative program, yet it fails completely restore functional mass. One component of this program epidermal growth factor receptor (EGFR) signaling. However, upon irreparable damage, EGFR signaling dampened, disrupting mass maintain normoglycemia. We previously demonstrated that negative feedback inhibitor EGFR, Mitogen-inducible...
Following autoimmune-mediated destruction of insulin secreting β-cells in type 1 diabetes (T1D), regenerative and repair pathways aim to restore β-cell mass maintain euglycemia. However, these are often unable compensate for the loss mass, resulting insufficient secretion chronic hyperglycemia. Our lab previously demonstrated that this inability may be at least part due mitogen inducible gene 6 (Mig6), an anti-proliferative negative feedback inhibitor epithelial growth factor receptor...
Strategies to promote β cell neogenesis could be used restore functional mass in both type 1 and 2 diabetes. Here we examine the role of mitogen-inducible gene 6 (mig6, a.k.a. erffi1) regulation mass. mig6 is evolutionarily conserved encodes a protein that inhibits epidermal growth factor receptor (EGFR) classic feedback mechanism, suggesting potential cellular development. Based on studies mouse human, hypothesized required pancreatic ducts for pancreatogenesis function. We morpholino...