Clinical Trials as Topic; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Endocrinology; Glucose; Hypoglycemia; Insulin
Obesity Research Working Group
Reversal of defective defenses against hypoglycemia in diabetes requires a better understanding of the mechanisms used to sense hypoglycemia and trigger defenses against hypoglycemia.
Specialized Terms: Glucose counterregulation; Brain fuel metabolism; Effect of insulin on brain function; Immune mechanisms leading to type 1 diabetes.
Extensive Research Description
Reversal of defective defenses against hypoglycemia in diabetes requires a better understanding of the mechanisms used to sense hypoglycemia and trigger glucose counterregulation. Dr. Sherwin’s laboratory has provided strong evidence that the ventromedial hypothalamus (VMH) plays a critical glucose-sensing role. Experiments in rodents exposed to recurrent hypoglycemia indicated that defective hormone secretion induced by antecedent iatrogenic hypoglycemia in diabetes could be explained by a failure of the VMH to activate counterregulatory responses. His laboratory is now focused on the molecular mechanisms used by the VMH to sense glucose, an area of importance not only for glucose counteregulation, but also for the regulation of feeding. He is testing the intriguing hypothesis that the VMH senses glucose via mechanisms similar to those used by the beta cell and that GABA neurotransmission is involved. This concept is supported by studies showing that like the beta cell local glucose availability regulates KATP channels in the VMH, which in turn modulate the release of counterregulatory hormones. A link with local VHM GABA neurotransmission is supported by data showing the activation state of VMH KATP channels modulates GABA levels in the VMH interstitial fluid. Thus, GABA release by beta cell-like neurons in the VMH could play an important role in modulating hormonal responses to hypoglycemia. The lab has also generated interesting data suggesting that this is not be the whole story. Some VMH glucose sensing neurons appear to use the enzyme AMP-K, which serves as a “fuel gauge” in a variety of cells in peripheral tissues, such as muscle. Reduction of AMP-K gene expression (bilateral VMH injection of AMP-K siRNA) suppresses glucose counterregulation. The lab is also examining the mechanism mediating defective glucose counterregulation after intensive treatment of diabetes., the major cause of severe hypoglycemia in patients. These studies suggest that multiple adaptive mechanisms may be involved including: upregulation of VMH CRFR2 recectors , increased VMH GABA tone and AMP-Kinase activity. These studies have generated plans for several novel therapeutic interventions to reduce hypoglycemia risk.
Research in immunology focuses on molecular and cell biology, genetically modified (transgenic) rodents, and immunobiology. We have generated diabetogenic and disease suppressive T cells that recognize peptides derived from beta cell autoantigens (GAD, and insulin) and modify disease expressio.. In addition, we have generated transgenic mice that express HLA genes linked to type 1 diabetes and hope to use these genetically altered mice to isolate and clone diabetes producing T lymphocytes from humans. Such cells may provide a tool for developing new strategies for immunotherapy. Finally, we are testing the hypothesis that the early insult to beta cells initiates a vicious circle involving attempted islet cell regeneration followed by enhanced autoimmunity. One of the targets of this autoimmune-response we believe is a family of proteins termed Reg that support islet regeneration and paradoxically generate an autoimmune response against beta cells in spontaneously diabetic NOD mice as well as humans with type 1 diabetes. Understanding this process might significantly affect current approaches to therapies.
Lactate-Induced Release of GABA in the Ventromedial Hypothalamus Contributes to Counterregulatory Failure in Recurrent Hypoglycemia and Diabetes.
Chan O, Paranjape S; Horblitt A; Zhu W; Sherwin, R. Lactate-Induced Release of GABA in the Ventromedial Hypothalamus Contributes to Counterregulatory Failure in Recurrent Hypoglycemia and Diabetes. Diabetes 62: 4239-4246, 2013.
Interactions Within the Ventromedial Hypothalamus Influence Counterregulatory Hormone Release and Local Glutamine/Glutamate Balance During Hypoglycemia
Szepietowska B, Zhu W, Czyzyk J, Eid T, Sherwin RS. EphA5-EphrinA5 Interactions Within the Ventromedial Hypothalamus Influence Counterregulatory Hormone Release and Local Glutamine/Glutamate Balance During Hypoglycemia. Diabetes. 62(4):1282-1288, 2013.
Circulating glucose levels modulate neural control of desire for high-calorie foods in humans.
Page KA*, Seo D*, Belfort-DeAguiar R, Lacadie C, Dzuira J, Naik S, Amarnath S, Constable T, Sherwin RS*, Sinha R*. Circulating glucose levels modulate neural control of desire for high-calorie foods in humans. J Clin Invest; 121:4161-4169, 2011. *equal contribution.
Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways
Page KA, Chan O, Arora J, Belfort-Deaguiar R, Dzuira J, Roehmholdt B, Cline GW, Naik S, Sinha R, Constable RT, Sherwin RS. Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways. JAMA. 309: 63-70, 2013.
Lactate preserves neuronal metabolism an function following antecedent recurrent hypoglycemia
Herzog RI, Jiang L, Herman P, Zhao C, Sanganahalli BG, Mason GF, Hyder F, Rothman,DL, Sherwin RS, Behar KL. Lactate preserves neuronal metabolism an function following antecedent recurrent hypoglycemia. J Clin Invest. 123: 1988-1998, 2013.
Corticotrophin releasing factor (CRF) receptors within the ventromedial hypothalamus (VMH) regulate hypoglycemia-induced hormonal counterregulation
McCrimmon RJ, Song Z, Cheng H, McNay EC, Weikart-Yeckel C, Fan X, Routh VH, Sherwin, RS. Corticotrophin releasing factor (CRF) receptors within the ventromedial hypothalamus (VMH) regulate hypoglycemia-induced hormonal counterregulation. J Clin Invest, 116:1723-1730, 2006.
In vivo evidence for the contribution of HLA-DQ molecules to the development of diabetes.
Wen L, Wong FS, Tan J, Chen N-Y, Altieri M, David C, Flavell R, Sherwin R. In vivo evidence for the contribution of HLA-DQ molecules to the development of diabetes. J Exp Med, 191:97-104, 2000.
Full List of PubMed Publications
- Li NX, Brown S, Kowalski T, Wu M, Yang L, Dai G, Petrov A, Ding Y, Dlugos T, Woods HB, Wang L, Erion M, Sherwin R, Kelley DE: GPR119 Agonism Increases Glucagon Secretion During Insulin-Induced Hypoglycemia. Diabetes. 2018 Apr 18; 2018 Apr 18. PMID: 29669745
- Hwang JJ, Parikh L, 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 Apr 2; 2018 Mar 5. PMID: 29381484
- Belfort-DeAguiar RD, 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 Mar 23; 2018 Mar 23. PMID: 29590401
- Belfort-DeAguiar R, Seo D, Lacadie C, Naik S, Schmidt C, Lam W, Hwang J, Constable T, Sinha R, Sherwin RS: Obese Humans Have Disordered Brain Responses to Food Images During Physiological Hyperglycemia. Am J Physiol Endocrinol Metab. 2018 Jan 30; 2018 Jan 30. PMID: 29381374
- Hwang JJ, Jiang L, Hamza M, Sanchez Rangel E, Dai F, Belfort-DeAguiar R, Parikh L, Koo BB, Rothman DL, Mason G, Sherwin RS: Blunted rise in brain glucose levels during hyperglycemia in adults with obesity and T2DM. JCI Insight. 2017 Oct 19; 2017 Oct 19. PMID: 29046482
- Gubitosi-Klug RA, Braffett BH, White NH, Sherwin RS, Service FJ, Lachin JM, Tamborlane WV, Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group.: Risk of Severe Hypoglycemia in Type 1 Diabetes Over 30 Years of Follow-up in the DCCT/EDIC Study. Diabetes Care. 2017 Aug; 2017 May 26. PMID: 28550194
- Naik S, Belfort-DeAguiar R, Sejling AS, Szepietowska B, Sherwin RS: Evaluation of the counter-regulatory responses to hypoglycaemia in patients with type 1 diabetes during opiate receptor blockade with naltrexone. Diabetes Obes Metab. 2017 May; 2017 Feb 17. PMID: 27987236
- Hwang JJ, Jiang L, Hamza M, Dai F, Belfort-DeAguiar R, Cline G, Rothman DL, Mason G, Sherwin RS: The human brain produces fructose from glucose. JCI Insight. 2017 Feb 23; 2017 Feb 23. PMID: 28239653
- Jastreboff AM, Sinha R, Arora J, Giannini C, Kubat J, Malik S, Van Name MA, Santoro N, Savoye M, Duran EJ, Pierpont B, Cline G, Constable RT, Sherwin RS, Caprio S: Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents. Diabetes. 2016 Jul; 2016 Apr 5. PMID: 27207544
- Stoeckel LE, Arvanitakis Z, Gandy S, Small D, Kahn CR, Pascual-Leone A, Pawlyk A, Sherwin R, Smith P: Complex mechanisms linking neurocognitive dysfunction to insulin resistance and other metabolic dysfunction. F1000Res. 2016; 2016 Mar 15. PMID: 27303627
- Reno CM, Ding Y, Sherwin R: Leptin acts in the brain to influence hypoglycemic counterregulation: disparate effects of acute and recurrent hypoglycemia on glucagon release. Am J Physiol Endocrinol Metab. 2015 Dec 15; 2015 Oct 27. PMID: 26506851
- Fan X, Chan O, Ding Y, Zhu W, Mastaitis J, Sherwin R: Reduction in SGLT1 mRNA Expression in the Ventromedial Hypothalamus Improves the Counterregulatory Responses to Hypoglycemia in Recurrently Hypoglycemic and Diabetic Rats. Diabetes. 2015 Oct; 2015 Jun 30. PMID: 26130763
- Belfort-DeAguiar RD, Naik S, Hwang J, Szepietowska B, Sherwin RS: Inhaled Formoterol Diminishes Insulin-Induced Hypoglycemia in Type 1 Diabetes. Diabetes Care. 2015 Sep; 2015 Jul 7. PMID: 26153273
- Hwang JJ, Johnson A, Cline G, Belfort-DeAguiar R, Snegovskikh D, Khokhar B, Han CS, Sherwin RS: Fructose levels are markedly elevated in cerebrospinal fluid compared to plasma in pregnant women. PLoS One. 2015; 2015 Jun 2. PMID: 26035307
- Hwang JJ, Yeckel CW, Gallezot JD, Aguiar RB, Ersahin D, Gao H, Kapinos M, Nabulsi N, Huang Y, Cheng D, Carson RE, Sherwin R, Ding YS: Imaging human brown adipose tissue under room temperature conditions with (11)C-MRB, a selective norepinephrine transporter PET ligand. Metabolism. 2015 Jun; 2015 Mar 5. PMID: 25798999
- Sun X, Kroemer NB, Veldhuizen MG, Babbs AE, de Araujo IE, Gitelman DR, Sherwin RS, Sinha R, Small DM: Basolateral amygdala response to food cues in the absence of hunger is associated with weight gain susceptibility. J Neurosci. 2015 May 20. PMID: 25995480
- Van Name M, Giannini C, Santoro N, Jastreboff AM, Kubat J, Li F, Kursawe R, Savoye M, Duran E, Dziura J, Sinha R, Sherwin RS, Cline G, Caprio S: Blunted suppression of acyl-ghrelin in response to fructose ingestion in obese adolescents: the role of insulin resistance. Obesity (Silver Spring). 2015 Mar; 2015 Feb 3. PMID: 25645909
- Jastreboff AM, Sinha R, Lacadie CM, Balodis IM, Sherwin R, Potenza MN: Blunted striatal responses to favorite-food cues in smokers. Drug Alcohol Depend. 2015 Jan 1; 2014 Sep 18. PMID: 25444233
- Jastreboff AM, Lacadie C, Seo D, Kubat J, Van Name MA, Giannini C, Savoye M, Constable RT, Sherwin RS, Caprio S, Sinha R: Leptin is associated with exaggerated brain reward and emotion responses to food images in adolescent obesity. Diabetes Care. 2014 Nov; 2014 Aug 19. PMID: 25139883
- Sun X, Veldhuizen MG, Wray AE, de Araujo IE, Sherwin RS, Sinha R, Small DM: The neural signature of satiation is associated with ghrelin response and triglyceride metabolism. Physiol Behav. 2014 Sep; 2014 Apr 13. PMID: 24732416
- Chan O, Sherwin RS: Is there cross talk between portal and hypothalamic glucose-sensing circuits? Diabetes. 2014 Aug. PMID: 25060894
- Szepietowska B, Horvath TL, Sherwin RS: Role of synaptic plasticity and EphA5-ephrinA5 interaction within the ventromedial hypothalamus in response to recurrent hypoglycemia. Diabetes. 2014 Mar; 2013 Nov 12. PMID: 24222347
- Belfort-Deaguiar R, Constable RT, Sherwin RS: Functional MRI signal fluctuations: a preclinical biomarker for cognitive impairment in type 2 diabetes? Diabetes. 2014 Feb. PMID: 24464717
- Chan O, Paranjape SA, Horblitt A, Zhu W, Sherwin RS: Lactate-induced release of GABA in the ventromedial hypothalamus contributes to counterregulatory failure in recurrent hypoglycemia and diabetes. Diabetes. 2013 Dec; 2013 Aug 12. PMID: 23939392
- Chan O, Sherwin R: Influence of VMH fuel sensing on hypoglycemic responses. Trends Endocrinol Metab. 2013 Dec; 2013 Sep 21. PMID: 24063974
- Szepietowska B, Zhu W, Sherwin RS: β2-Adrenergic receptor agonist administration promotes counter-regulatory responses and recovery from hypoglycaemia in rats. Diabetologia. 2013 Nov; 2013 Aug 10. PMID: 23933834
- Gulanski BI, De Feyter HM, Page KA, Belfort-DeAguiar R, Mason GF, Rothman DL, Sherwin RS: Increased brain transport and metabolism of acetate in hypoglycemia unawareness. J Clin Endocrinol Metab. 2013 Sep; 2013 Jun 24. PMID: 23796565
- Gurr W, Shaw M, Herzog RI, Li Y, Sherwin R: Vaccination with single chain antigen receptors for islet-derived peptides presented on I-A(g7) delays diabetes in NOD mice by inducing anergy in self-reactiveT-cells. PLoS One. 2013; 2013 Jul 24. PMID: 23894487
- Herzog RI, Jiang L, Herman P, Zhao C, Sanganahalli BG, Mason GF, Hyder F, Rothman DL, Sherwin RS, Behar KL: Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia. J Clin Invest. 2013 May; 2013 Apr 1. PMID: 23543056
- Szepietowska B, Zhu W, Czyzyk J, Eid T, Sherwin RS: EphA5-EphrinA5 interactions within the ventromedial hypothalamus influence counterregulatory hormone release and local glutamine/glutamate balance during hypoglycemia. Diabetes. 2013 Apr; 2012 Dec 28. PMID: 23274893
- Singh R, De Aguiar RB, Naik S, Mani S, Ostadsharif K, Wencker D, Sotoudeh M, Malekzadeh R, Sherwin RS, Mani A: LRP6 enhances glucose metabolism by promoting TCF7L2-dependent insulin receptor expression and IGF receptor stabilization in humans. Cell Metab. 2013 Feb 5. PMID: 23395167
- Jastreboff AM, Sinha R, Lacadie C, Small DM, Sherwin RS, Potenza MN: Neural correlates of stress- and food cue-induced food craving in obesity: association with insulin levels. Diabetes Care. 2013 Feb; 2012 Oct 15. PMID: 23069840
- Page KA, Chan O, Arora J, Belfort-Deaguiar R, Dzuira J, Roehmholdt B, Cline GW, Naik S, Sinha R, Constable RT, Sherwin RS: Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways. JAMA. 2013 Jan 2. PMID: 23280226
- Sherwin R, Slayman C, Rockwell S, Herold K, Williams K, Carson R, Mane S, Seow H, Max J, Johnson T: Yale Center for Clinical Investigation: leveraging industry partnerships and research cores. Clin Transl Sci. 2012 Dec. PMID: 23253663
- Lin SF, Fan X, Yeckel CW, Weinzimmer D, Mulnix T, Gallezot JD, Carson RE, Sherwin RS, Ding YS: Ex vivo and in vivo evaluation of the norepinephrine transporter ligand [11C]MRB for brown adipose tissue imaging. Nucl Med Biol. 2012 Oct; 2012 May 16. PMID: 22595487
- Chan O, Sherwin RS: Hypothalamic regulation of glucose-stimulated insulin secretion. Diabetes. 2012 Mar. PMID: 22354931
- Herzog RI, Sherwin RS: Diabetes. Can tight glycemic control in diabetes benefit cognition? Nat Rev Neurol. 2012 Jan 31; 2012 Jan 31. PMID: 22290574
- Szepietowska B, Zhu W, Chan O, Horblitt A, Dziura J, Sherwin RS: Modulation of β-adrenergic receptors in the ventromedial hypothalamus influences counterregulatory responses to hypoglycemia. Diabetes. 2011 Dec; 2011 Oct 19. PMID: 22013013
- Paranjape SA, Chan O, Zhu W, Horblitt AM, Grillo CA, Wilson S, Reagan L, Sherwin RS: Chronic reduction of insulin receptors in the ventromedial hypothalamus produces glucose intolerance and islet dysfunction in the absence of weight gain. Am J Physiol Endocrinol Metab. 2011 Nov; 2011 Aug 9. PMID: 21828334
- Wira CR 3rd, Rivers E, Martinez-Capolino C, Silver B, Iyer G, Sherwin R, Lewandowski C: Cardiac complications in acute ischemic stroke. West J Emerg Med. 2011 Nov. PMID: 22224130
- Page KA, Seo D, Belfort-DeAguiar R, Lacadie C, Dzuira J, Naik S, Amarnath S, Constable RT, Sherwin RS, Sinha R: Circulating glucose levels modulate neural control of desire for high-calorie foods in humans. J Clin Invest. 2011 Oct; 2011 Sep 19. PMID: 21926468
- Herzog RI, Sherwin RS, Rothman DL: Insulin-induced hypoglycemia and its effect on the brain: unraveling metabolism by in vivo nuclear magnetic resonance. Diabetes. 2011 Jul. PMID: 21709281
- Tai N, Yasuda H, Xiang Y, Zhang L, Rodriguez-Pinto D, Yokono K, Sherwin R, Wong FS, Nagata M, Wen L: IL-10-conditioned dendritic cells prevent autoimmune diabetes in NOD and humanized HLA-DQ8/RIP-B7.1 mice. Clin Immunol. 2011 Jun; 2011 Mar 9. PMID: 21458378
- Chan O, Paranjape S, Czyzyk D, Horblitt A, Zhu W, Ding Y, Fan X, Seashore M, Sherwin R: Increased GABAergic output in the ventromedial hypothalamus contributes to impaired hypoglycemic counterregulation in diabetic rats. Diabetes. 2011 May; 2011 Mar 16. PMID: 21411513
- Jastreboff AM, Potenza MN, Lacadie C, Hong KA, Sherwin RS, Sinha R: Body mass index, metabolic factors, and striatal activation during stressful and neutral-relaxing states: an FMRI study. Neuropsychopharmacology. 2011 Feb; 2010 Nov 3. PMID: 21048702
- Paranjape SA, Chan O, Zhu W, Horblitt AM, McNay EC, Cresswell JA, Bogan JS, McCrimmon RJ, Sherwin RS: Influence of insulin in the ventromedial hypothalamus on pancreatic glucagon secretion in vivo. Diabetes. 2010 Jun; 2010 Mar 18. PMID: 20299468
- Zhu W, Czyzyk D, Paranjape SA, Zhou L, Horblitt A, Szabó G, Seashore MR, Sherwin RS, Chan O: Glucose prevents the fall in ventromedial hypothalamic GABA that is required for full activation of glucose counterregulatory responses during hypoglycemia. Am J Physiol Endocrinol Metab. 2010 May; 2010 Feb 9. PMID: 20304763
- Jiang L, Herzog RI, Mason GF, de Graaf RA, Rothman DL, Sherwin RS, Behar KL: Recurrent antecedent hypoglycemia alters neuronal oxidative metabolism in vivo. Diabetes. 2009 Jun; 2009 Mar 10. PMID: 19276443
- Page KA, Williamson A, Yu N, McNay EC, Dzuira J, McCrimmon RJ, Sherwin RS: Medium-chain fatty acids improve cognitive function in intensively treated type 1 diabetic patients and support in vitro synaptic transmission during acute hypoglycemia. Diabetes. 2009 May; 2009 Feb 17. PMID: 19223595
- Page KA, Arora J, Qiu M, Relwani R, Constable RT, Sherwin RS: Small decrements in systemic glucose provoke increases in hypothalamic blood flow prior to the release of counterregulatory hormones. Diabetes. 2009 Feb; 2008 Nov 18. PMID: 19017765
- Fan X, Ding Y, Cheng H, Gram DX, Sherwin RS, McCrimmon RJ: Amplified hormonal counterregulatory responses to hypoglycemia in rats after systemic delivery of a SUR-1-selective K(+) channel opener? Diabetes. 2008 Dec; 2008 Sep 5. PMID: 18776135
- Sherwin RS: Bringing light to the dark side of insulin: a journey across the blood-brain barrier. Diabetes. 2008 Sep. PMID: 18753671
- Chan O, Cheng H, Herzog R, Czyzyk D, Zhu W, Wang A, McCrimmon RJ, Seashore MR, Sherwin RS: Increased GABAergic tone in the ventromedial hypothalamus contributes to suppression of counterregulatory responses after antecedent hypoglycemia. Diabetes. 2008 May; 2008 Mar 28. PMID: 18375441
- Herzog RI, Chan O, Yu S, Dziura J, McNay EC, Sherwin RS: Effect of acute and recurrent hypoglycemia on changes in brain glycogen concentration. Endocrinology. 2008 Apr; 2008 Jan 10. PMID: 18187548
- McCrimmon RJ, Shaw M, Fan X, Cheng H, Ding Y, Vella MC, Zhou L, McNay EC, Sherwin RS: Key role for AMP-activated protein kinase in the ventromedial hypothalamus in regulating counterregulatory hormone responses to acute hypoglycemia. Diabetes. 2008 Feb; 2007 Oct 31. PMID: 17977955
- Cheng H, Zhou L, Zhu W, Wang A, Tang C, Chan O, Sherwin RS, McCrimmon RJ: Type 1 corticotropin-releasing factor receptors in the ventromedial hypothalamus promote hypoglycemia-induced hormonal counterregulation. Am J Physiol Endocrinol Metab. 2007 Sep; 2007 Jun 19. PMID: 17578887
- Chan O, Lawson M, Zhu W, Beverly JL, Sherwin RS: ATP-sensitive K(+) channels regulate the release of GABA in the ventromedial hypothalamus during hypoglycemia. Diabetes. 2007 Apr; 2007 Jan 24. PMID: 17251273
- Driesen NR, Goldberg PA, Anderson AW, Tang L, Flanagan DE, Sherwin RS, Gore JC: Hypoglycemia reduces the blood-oxygenation level dependent signal in primary auditory and visual cortex: a functional magnetic resonance imaging study. J Neurosci Res. 2007 Feb 15. PMID: 17154420
- Gurr W, Shaw M, Li Y, Sherwin R: RegII is a beta-cell protein and autoantigen in diabetes of NOD mice. Diabetes. 2007 Jan. PMID: 17192462
- McCrimmon RJ, Fan X, Cheng H, McNay E, Chan O, Shaw M, Ding Y, Zhu W, Sherwin RS: Activation of AMP-activated protein kinase within the ventromedial hypothalamus amplifies counterregulatory hormone responses in rats with defective counterregulation. Diabetes. 2006 Jun. PMID: 16731839
- McCrimmon RJ, Song Z, Cheng H, McNay EC, Weikart-Yeckel C, Fan X, Routh VH, Sherwin RS: Corticotrophin-releasing factor receptors within the ventromedial hypothalamus regulate hypoglycemia-induced hormonal counterregulation. J Clin Invest. 2006 Jun. PMID: 16741581
- Du W, Wong FS, Li MO, Peng J, Qi H, Flavell RA, Sherwin R, Wen L: TGF-beta signaling is required for the function of insulin-reactive T regulatory cells. J Clin Invest. 2006 May. PMID: 16670772
- Goldberg PA, Weiss R, McCrimmon RJ, Hintz EV, Dziura JD, Sherwin RS: Antecedent hypercortisolemia is not primarily responsible for generating hypoglycemia-associated autonomic failure. Diabetes. 2006 Apr. PMID: 16567537
- McNay EC, Williamson A, McCrimmon RJ, Sherwin RS: Cognitive and neural hippocampal effects of long-term moderate recurrent hypoglycemia. Diabetes. 2006 Apr. PMID: 16567533
- Chan O, Zhu W, Ding Y, McCrimmon RJ, Sherwin RS: Blockade of GABA(A) receptors in the ventromedial hypothalamus further stimulates glucagon and sympathoadrenal but not the hypothalamo-pituitary-adrenal response to hypoglycemia. Diabetes. 2006 Apr. PMID: 16567532
- Diano S, Farr SA, Benoit SC, McNay EC, da Silva I, Horvath B, Gaskin FS, Nonaka N, Jaeger LB, Banks WA, Morley JE, Pinto S, Sherwin RS, Xu L, Yamada KA, Sleeman MW, Tschöp MH, Horvath TL: Ghrelin controls hippocampal spine synapse density and memory performance. Nat Neurosci. 2006 Mar; 2006 Feb 19. PMID: 16491079
- McNay EC, Canal CE, Sherwin RS, Gold PE: Modulation of memory with septal injections of morphine and glucose: effects on extracellular glucose levels in the hippocampus. Physiol Behav. 2006 Feb 28; 2005 Dec 15. PMID: 16343563
- McCrimmon RJ, Evans ML, Fan X, McNay EC, Chan O, Ding Y, Zhu W, Gram DX, Sherwin RS: Activation of ATP-sensitive K+ channels in the ventromedial hypothalamus amplifies counterregulatory hormone responses to hypoglycemia in normal and recurrently hypoglycemic rats. Diabetes. 2005 Nov. PMID: 16249441
- Inzucchi SE, Sherwin RS: The prevention of type 2 diabetes mellitus. Endocrinol Metab Clin North Am. 2005 Mar. PMID: 15752928
- Cavus I, Kasoff WS, Cassaday MP, Jacob R, Gueorguieva R, Sherwin RS, Krystal JH, Spencer DD, Abi-Saab WM: Extracellular metabolites in the cortex and hippocampus of epileptic patients. Ann Neurol. 2005 Feb. PMID: 15668975
- Yeckel CW, Taksali SE, Dziura J, Weiss R, Burgert TS, Sherwin RS, Tamborlane WV, Caprio S: The normal glucose tolerance continuum in obese youth: evidence for impairment in beta-cell function independent of insulin resistance. J Clin Endocrinol Metab. 2005 Feb; 2004 Nov 2. PMID: 15522932
- Evans ML, McCrimmon RJ, Flanagan DE, Keshavarz T, Fan X, McNay EC, Jacob RJ, Sherwin RS: Hypothalamic ATP-sensitive K + channels play a key role in sensing hypoglycemia and triggering counterregulatory epinephrine and glucagon responses. Diabetes. 2004 Oct. PMID: 15448082
- McCrimmon RJ, Fan X, Ding Y, Zhu W, Jacob RJ, Sherwin RS: Potential role for AMP-activated protein kinase in hypoglycemia sensing in the ventromedial hypothalamus. Diabetes. 2004 Aug. PMID: 15277372
- Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, Allen K, Lopes M, Savoye M, Morrison J, Sherwin RS, Caprio S: Obesity and the metabolic syndrome in children and adolescents. N Engl J Med. 2004 Jun 3. PMID: 15175438
- Goldberg PA, Siegel MD, Russell RR, Sherwin RS, Halickman JI, Cooper DA, Dziura JD, Inzucchi SE: Experience with the continuous glucose monitoring system in a medical intensive care unit. Diabetes Technol Ther. 2004 Jun. PMID: 15198837
- McNay EC, Sherwin RS: Effect of recurrent hypoglycemia on spatial cognition and cognitive metabolism in normal and diabetic rats. Diabetes. 2004 Feb. PMID: 14747293
- Goldberg PA, Siegel MD, Sherwin RS, Halickman JI, Lee M, Bailey VA, Lee SL, Dziura JD, Inzucchi SE: Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit. Diabetes Care. 2004 Feb. PMID: 14747229
- McNay EC, Sherwin RS: From artificial cerebro-spinal fluid (aCSF) to artificial extracellular fluid (aECF): microdialysis perfusate composition effects on in vivo brain ECF glucose measurements. J Neurosci Methods. 2004 Jan 15. PMID: 14687673
- Weiss R, Dufour S, Taksali SE, Tamborlane WV, Petersen KF, Bonadonna RC, Boselli L, Barbetta G, Allen K, Rife F, Savoye M, Dziura J, Sherwin R, Shulman GI, Caprio S: Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning. Lancet. 2003 Sep 20. PMID: 14511928
- Enoksson S, Caprio SK, Rife F, Shulman GI, Tamborlane WV, Sherwin RS: Defective activation of skeletal muscle and adipose tissue lipolysis in type 1 diabetes mellitus during hypoglycemia. J Clin Endocrinol Metab. 2003 Apr. PMID: 12679430
- Borg MA, Tamborlane WV, Shulman GI, Sherwin RS: Local lactate perfusion of the ventromedial hypothalamus suppresses hypoglycemic counterregulation. Diabetes. 2003 Mar. PMID: 12606506
- Flanagan DE, Keshavarz T, Evans ML, Flanagan S, Fan X, Jacob RJ, Sherwin RS: Role of corticotrophin-releasing hormone in the impairment of counterregulatory responses to hypoglycemia. Diabetes. 2003 Mar. PMID: 12606499
- Flanagan DE, Evans ML, Monsod TP, Rife F, Heptulla RA, Tamborlane WV, Sherwin RS: The influence of insulin on circulating ghrelin. Am J Physiol Endocrinol Metab. 2003 Feb. PMID: 12531744
- Monsod TP, Flanagan DE, Rife F, Saenz R, Caprio S, Sherwin RS, Tamborlane WV: Do sensor glucose levels accurately predict plasma glucose concentrations during hypoglycemia and hyperinsulinemia? Diabetes Care. 2002 May. PMID: 11978686
- Evans ML, Sherwin RS: Blood glucose and the brain in diabetes: between a rock and a hard place? Curr Diab Rep. 2002 Apr. PMID: 12643129
- Wen L, Wong FS, Sherwin R, Mora C: Human DQ8 can substitute for murine I-Ag7 in the selection of diabetogenic T cells restricted to I-Ag7. J Immunol. 2002 Apr 1. PMID: 11907129
- Sinha R, Fisch G, Teague B, Tamborlane WV, Banyas B, Allen K, Savoye M, Rieger V, Taksali S, Barbetta G, Sherwin RS, Caprio S: Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med. 2002 Mar 14. PMID: 11893791
- Abi-Saab WM, Maggs DG, Jones T, Jacob R, Srihari V, Thompson J, Kerr D, Leone P, Krystal JH, Spencer DD, During MJ, Sherwin RS: Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia. J Cereb Blood Flow Metab. 2002 Mar. PMID: 11891432
- Gurr W, Yavari R, Wen L, Shaw M, Mora C, Christa L, Sherwin RS: A Reg family protein is overexpressed in islets from a patient with new-onset type 1 diabetes and acts as T-cell autoantigen in NOD mice. Diabetes. 2002 Feb. PMID: 11812740