A5044916299- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Erythrocyte Function and Pathophysiology
- Cannabis and Cannabinoid Research
- Adipose Tissue and Metabolism
- Diabetes Treatment and Management
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Autism Spectrum Disorder Research
- Electrolyte and hormonal disorders
- Receptor Mechanisms and Signaling
- Neonatal Health and Biochemistry
- Genetics and Neurodevelopmental Disorders
- Adenosine and Purinergic Signaling
- Epigenetics and DNA Methylation
- Behavioral and Psychological Studies
- Cardiac Ischemia and Reperfusion
- Animal Behavior and Welfare Studies
University of Wisconsin–Madison
2020-2023
Madison Group (United States)
2021
Florida Institute of Technology
2018
Pyruvate kinase (PK) and the phosphoenolpyruvate (PEP) cycle play key roles in nutrient-stimulated KATP channel closure insulin secretion. To identify PK isoforms involved, we generated mice lacking β-cell PKm1, PKm2, mitochondrial PEP carboxykinase (PCK2) that generates PEP. Glucose metabolism was found to generate both glycolytic mitochondrially derived PEP, which triggers through local PKm1 PKm2 signaling at plasma membrane. Amino acids, without producing fructose 1,6-bisphosphate...
The ATP-sensitive K
Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined architecture of targets that regulate GLP-1 action male cells. cooperates with enhance cAMP production at plasma membrane and endosomes via: (1) increased mitochondrial CO2, activating HCO3−-sensitive soluble adenylate...
Resurgence is defined as the recurrence of a previously reinforced and then extinguished target response when reducing or eliminating more recently alternative response. In experiments with children pigeons, we evaluated patterns resurgence across within sessions through decreases in reinforcer availability by challenging responding extinction progressive‐ratio schedules. Phase 1, only responding. 2, while reinforcing an Finally, 3 assessed (a) extinguishing versus (b) introducing schedule...
Hallmarks of mature β cells are restricted proliferation and a highly energetic secretory state. Paradoxically, cyclin-dependent kinase 2 (CDK2) is synthesized throughout adulthood, its cytosolic localization raising the likelihood cell cycle-independent functions. In absence any changes in mass, maturity, or proliferation, genetic deletion Cdk2 adult enhanced insulin secretion from isolated islets improved glucose tolerance vivo. At single level, CDK2 restricts by increasing KATP...
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 pyruvate, underlies β-cell sensing of both glycolytic mitochondrial fuels. PK present at the plasma membrane is sufficient to close K channels initiate calcium influx. Small-molecule activators increase oscillation frequency potently amplify By cyclically depriving mitochondria ADP, restricts oxidative...
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 pyruvate, underlies β-cell sensing of both glycolytic mitochondrial fuels. PK present at the plasma membrane is sufficient to close KATP channels initiate calcium influx. Small-molecule activators increase oscillation frequency potently amplify By cyclically depriving mitochondria ADP, restricts oxidative...
SUMMARY Pyruvate kinase (PK) and the phosphoenolpyruvate (PEP) cycle play key roles in nutrient-stimulated K ATP channel closure insulin secretion. To identify PK isoforms involved, we generated mice lacking β-cell PKm1, PKm2, mitochondrial PEP carboxykinase (PCK2) that generates PEP. Glucose metabolism both glycolytic mitochondrially-derived PEP, which triggers through local PKm1 PKm2 signaling at plasma membrane. Amino acids, generate without producing fructose 1,6-bisphosphate to...
Summary The ATP-sensitive K + channel (K ATP ) is a key regulator of hormone secretion from pancreatic islet endocrine cells. Using direct measurements activity in β cells and the lesser-studied α cells, both humans mice, we demonstrate that glycolytic metabolon locally controls channels on plasma membrane. two ATP-consuming enzymes upper glycolysis, glucokinase phosphofructokinase, generate ADP activates . Substrate channeling fructose 1,6-bisphosphate through lower glycolysis fuels...
The ATP-sensitive K+ channel (KATP) is a key regulator of hormone secretion from pancreatic islet endocrine cells. Using direct measurements KATP activity in β cells and the lesser-studied α cells, both humans mice, we demonstrate that glycolytic metabolon locally controls channels on plasma membrane. two ATP-consuming enzymes upper glycolysis, glucokinase phosphofructokinase, generate ADP activates KATP. Substrate channeling fructose 1,6-bisphosphate through lower glycolysis fuels pyruvate...
Pancreatic β-cells couple nutrient metabolism with appropriate insulin secretion. Here, we examined the requirements of pyruvate kinase (PK) isoforms in fuel sensing through β-cell specific deletion consititutively active PKM1 and allosterically recruitable PKM2 (PKM1- βKO, PKM2-βKO). PEP carboxykinase (PCK2-βKO) was used to block mitochondrial production, leaving glycolytic production intact. In vivo, only PKM1-βKO mice showed glucose intolerance, ex vivo secretion correspondingly reduced....
The ATP-sensitive potassium channel (KATP) is a key regulator of membrane potential and islet hormone secretion. In ß-cells, it has been previously showed that the local activity pyruvate kinase (PK) can sufficiently raise ATP/ADP to induce KATP closure, thus providing another route trigger depolarization parallel mitochondrial oxidative phosphorylation. Here, using direct single-channel measurements in both ß-and lesser studied α-cells, we provide evidence for larger network metabolic...