Publications

Google Scholar

Investigating the impact of obesity, insulin resistance and Type 2 Diabetes Mellitus (T2DM) on cerebral metabolism and function. Recently, work in our lab has observed that individuals with poorly controlled T2DM have altered brain glucose transport kinetics suggestive of adaptive mechanisms to chronic hyperglycemia. Furthermore, we have also observed that individuals with obesity, who do not have diabetes or hyperglycemia, also have decreased brain glucose transport kinetics. The potential mechanisms underlying these observations are the subject of several ongoing translational projects in our lab.

  • Gunawan F, Matson B, Coppoli A, Jiang L, Perry R, Sanchez-Rangel E, Belfort DeAguiar, Behar K, Rothman D, Mason GF, Hwang, JJ. Deficits in brain glucose transport amongst younger adults with obesity. Obesity 2024 1-10 PMID

  • Sanchez Rangel E, Gunawan F, Jiang L, Savoye M, Dai F, Coppoli A, Rothman DL, Mason GF, Hwang JJ. Reversibility of brain glucose kinetics in type 2 diabetes mellitus. Diabetologia 2022. PMID: 35247067.

  • Hwang, JJ, Jiang L, Hamza M, Belfort-DeAguiar R, Dai F, Koo B, Rothman D, Mason G, Sherwin RS. Blunted rise in brain glucose in obesity and T2DM. J Clin Invest Insight 2017 2(20). PMID: 29046482.

  • Belfort-DeAguiar R, Seo D, Lacadie C, Naik S, Schmidt C, Lam W, Hwang J, Constable T, Sinha R, Sherwin RS. Humans with obesity have disordered brain responses to food images during physiological hyperglycemia. Am J Physiol Endocrinol Metab. 2018 May 1;314(5):E522-E529. PMID: 29381374.

Investigating the impact of Type 1 Diabetes Mellitus (T1DM) and hypoglycemic unawareness on cerebral metabolism and function. Repeated exposure to hypoglycemia often leads to unawareness of hypoglycemia. Using state of the art neuroimaging technology including functional MRI and magnetic resonance spectroscopy coupled with classic human metabolic phenotyping methodologies, my group has conducted a series of experiments to show that glucose transport into the brain amongst individuals with T1DM can be modified by a variety of factors including hyperglycemia, hypoglycemia, and glycemic variability. These findings and ongoing work in the lab may have important implications for understanding the neurocognitive changes associated with T1DM.

  • Parikh L, Seo D, Lacadie C, Belfort DeAguiar R, Groskreutz D, Hamza M, Dai F, Scheinost D, Sinha R, Constable RT, Sherwin RS, Hwang JJ. Differential resting state connectivity responses to glycemic state in type 1 diabetes. J Clin Endocrinol Metab. 2020 105(1). PMID: 31511876.

  • Hwang JJ, Jiang L, Rangel ES,  Fan X,  Ding  Y,  Lam W, Leventhal J,  Dai  F,  Rothman DL,  Mason GF, Sherwin RS. Glycemic variability and brain glucose levels in T1DM. Diabetes 2019 68:163. PMID: 30327383.

  • Hwang JJ, Parikh, Lacadie C, Seo D, Lam W, Hamza M, Schmidt C, Dai F, Sejling AS, Belfort-DeAguiar R, Constable RT, Sinha R, Sherwin R. Hypoglycemia unawareness in Type 1 diabetes suppresses brain responses to hypoglycemia. J Clin Invest  2018 128(4):1485-1495. PMID: 29381484.

  • Belfort-DeAguiar R, Gallezot JD, Hwang JJ, Elshafie A, Yeckel CW, Chan O, Carson RE, Ding YS, Sherwin RS. Noradrenergic Activity in the Human Brain: A Mechanism Supporting the Defense Against Hypoglycemia. J Clin Endocrinol Metab. 2018 Jun 1;103(6):2244-2252. PMID: 29590401.

Endogenous central nervous system fructose production in the human brain. Although fructose has been implicated in the pathogenesis of obesity and type 2 diabetes (T2DM) and studies have suggested that fructose and glucose have differential central nervous system effects on feeding behavior, whether dietary fructose crosses the blood-brain barrier in levels sufficient to generate its CNS effects remains unclear. I have worked to understand the contribution of the polyol pathway, an alternate glucose pathway that bypasses glycolysis, to endogenous human brain fructose production. Our group showed that cerebrospinal fluid (CSF) fructose levels were nearly 20-times higher than plasma levels and correlated positively with CSF glucose and CSF sorbitol.

  • Hwang JJ, Johnson A, Belfort R, Cline G, Khokhar B, Snegovskikh D, Han C, and Sherwin RS. Fructose levels are significantly elevated in cerebrospinal fluid compared to plasma in pregnant women PLoS One 2015 Jun 2 10(6):e0128582. PMID: 26035307.

  • Hwang, JJ, Jiang L, Hamza M, Belfort-DeAguiar R, Dai F, Cline G, Rothman D, Mason G, Sherwin RS. The human brain produces fructose from glucose. J Clin Invest Insight 2017 2(4):e90508. PMID: 28239653.

Developing a novel PET radioligand for assessment of sympathetic nervous system with applications for metabolic disease. Brown adipose tissue (BAT) activity is tightly regulated by the sympathetic nervous system (SNS), and basal sympathetic tone of BAT is critical to all aspects of BAT function including browning of white adipose tissue (WAT), brown adipocyte differentiation and proliferation as well as determining the maximal thermogenic capacity of BAT. In a close collaboration with investigators in the Yale PET center, I validated the use of 11C-MRB ((S,S)-11C-O- methylreboxetine), a highly selective PET ligand for the norepinephrine transporter (NET), for imaging human BAT under room temperature conditions.

  • Hwang JJ, Yeckel C, Gallezot JD, Belfort R, Ersahim D, Goa H, Kapinos M, Nabulsi N, Huang Y, Cheng D, Carson R, Sherwin RS, Ding Y. Imaging human brown adipose tissue under room temperature conditions with 11C-MRB, a selective norepinephrine transporter PET ligand. Metabolism 2015 64(6):747-55. PMID: 25798999.

  • Sanchez-Rangel E, Gallezot J, Yeckel C, Lam W, Belfort-DeAguiar R, Chen M, Carson R, Sherwin R, Hwang JJ. Norepinephrine transporter availability in brown fat is reduced in obesity: A human PET study with [11C] MRB. Int J Obes (Lond). 2020 44(4):964. PMID: 31636373.

Contact Us

Brain Metabolism Lab at UNC School of Medicine

Division of the Endocrinology and Metabolism

BrainMetabolismLab@med.unc.edu

 

Biomedical Research Imaging Center at UNC

125 Mason Farm Road Marsico, Hall, Chapel Hill, NC 27514

 

Brain Metabolism Lab

Burnett-Womack Building, 160 Dental Cir, Chapel Hill, NC 27514