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High plasma VEGF relates to low carbohydrate intake in patients with type 2 diabetes

International Journal of Obesity volume 30, pages 1356–1361 (2006)Cite this article

Abstract

Objective:

Vascular endothelial growth factor (VEGF) has been suggested to enhance glucose transport across the blood–brain barrier, thereby increasing brain glucose supply. Increased brain glucose concentration is known to suppress food intake and to decrease body mass via action on hypothalamic regulation centers. Based on the crucial role of VEGF on brain glucose supply, we hypothesized that higher VEGF concentrations are associated with lower food intake and body mass in humans.

Methods:

Intending to investigate subjects with high variance of blood glucose, we examined patients with type 2 diabetes mellitus. Our hypothesis was tested in a population-based cohort of 190 subjects with type 2 diabetes. Plasma VEGF levels in conjunction with other parameters known to modulate food intake were measured and subsequently correlated with food intake patterns at a breakfast buffet as well as with body mass.

Results:

We found that subjects with higher concentrations of plasma VEGF had 17% less carbohydrate intake (P=0.003) and 4.8% lower body mass (P=0.017) than those with lower VEGF concentrations. Intake of protein and fat did not correlate with VEGF concentrations. These associations of plasma VEGF were confirmed in multiple linear regression analyses controlling for several parameters interacting with food intake.

Conclusion:

We conclude that high plasma VEGF concentrations are associated with less carbohydrate intake and lower body mass in type 2 diabetes. The role VEGF plays in facilitating glucose access to the brain represents a new aspect of food intake regulation and energy homeostasis, with relevance for diseases with body mass disturbances.

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References

  1. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289: 76–79.

    Article  PubMed  Google Scholar 

  2. Peters A, Schweiger U, Fruhwald-Schultes B, Born J, Fehm HL . The Neuroendocrine Control of Glucose Allocation. Exp Clin Endocrinol Diabetes 2002; 110: 199–211.

    Article  CAS  PubMed  Google Scholar 

  3. Peters A, Schweiger U, Pellerin L, Hubold C, Oltmanns KM, Conrad M et al. The Selfish Brain: Competition for Energy Resources. Neurosci Biobehav Rev 2004; 28: 143–180.

    Article  CAS  PubMed  Google Scholar 

  4. Davis JD, Wirtshafter D, Asin KE, Brief D . Sustained Intracerebroventricular Infusion of Brain Fuels Reduces Body Weight and Food Intake in Rats. Science 3-4-1981; 212: 81–83.

    Article  Google Scholar 

  5. Oomura Y, Ooyama H, Sugimori M, Nakamura T, Yamada Y . Glucose Inhibition of the Glucose-Sensitive Neurone in the Rat Lateral Hypothalamus. Nature 1-2-1974; 247: 284–286.

    Article  Google Scholar 

  6. Pardridge WM, Boado RJ, Farrell CR . Brain-Type Glucose Transporter (GLUT-1) Is Selectively Localized to the Blood-Brain Barrier. Studies With Quantitative Western Blotting and in Situ Hybridization. J Biol Chem 1990; 265: 18035–18040.

    CAS  PubMed  Google Scholar 

  7. Mani N, Khaibullina A, Krum JM, Rosenstein JM . Activation of Receptor-Mediated Angiogenesis and Signaling Pathways After VEGF Administration in Fetal Rat CNS Explants. J Cereb Blood Flow Metab 2003; 23: 1420–1429.

    Article  CAS  PubMed  Google Scholar 

  8. Sone H, Deo BK, Kumagai AK . Enhancement of Glucose Transport by Vascular Endothelial Growth Factor in Retinal Endothelial Cells. Invest Ophthalmol Vis Sci 2000; 41: 1876–1884.

    CAS  PubMed  Google Scholar 

  9. Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP et al. Endothelial Cells in Physiology and in the Pathophysiology of Vascular Disorders. Blood 15-5-1998; 91: 3527–3561.

    Google Scholar 

  10. Ferrara N . Vascular Endothelial Growth Factor: Basic Science and Clinical Progress. Endocr Rev 2004; 25: 581–611.

    Article  CAS  PubMed  Google Scholar 

  11. Pekala P, Marlow M, Heuvelman D, Connolly D . Regulation of Hexose Transport in Aortic Endothelial Cells by Vascular Permeability Factor and Tumor Necrosis Factor-Alpha, but Not by Insulin. J Biol Chem 25-10-1990; 265: 18051–18054.

    Google Scholar 

  12. Wang W, Merrill MJ, Borchardt RT . Vascular Endothelial Growth Factor Affects Permeability of Brain Microvessel Endothelial Cells in Vitro. Am J Physiol 1996; 271 (6 Pt 1): C1973–C1980.

    Article  CAS  PubMed  Google Scholar 

  13. Dantz D, Bewersdorf J, Fruehwald-Schultes B, Kern W, Jelkmann W, Born J et al. Vascular Endothelial Growth Factor: a Novel Endocrine Defensive Response to Hypoglycemia. J Clin Endocrinol Metab 2002; 87: 835–840.

    Article  CAS  PubMed  Google Scholar 

  14. Gavin JR, Alberti KGMM, Davidson MB, DeFronzo RA, Drash A, Gabbe SG et al. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2003; 26 (Suppl 1): S5–S20.

    Google Scholar 

  15. Pudel V, Westenhoefer J . Fragebogen zum EĂźverhalten: Handanweisung. Goettingen: Hogrefe, 1989.

    Google Scholar 

  16. Karschin C, Ecke C, Ashcroft FM, Karschin A . Overlapping Distribution of K(ATP) Channel-Forming Kir6.2 Subunit and the Sulfonylurea Receptor SUR1 in Rodent Brain. FEBS Lett 1997; 401: 59–64.

    Article  CAS  PubMed  Google Scholar 

  17. Levin BE, Dunn-Meynell AA, Routh VH . Brain Glucose Sensing and Body Energy Homeostasis: Role in Obesity and Diabetes. Am J Physiol 1999; 276 (5 Pt 2): R1223–R1231.

    CAS  PubMed  Google Scholar 

  18. Sergeyev V, Broberger C, Gorbatyuk O, Hokfelt T . Effect of 2-Mercaptoacetate and 2-Deoxy-D-Glucose Administration on the Expression of NPY, AGRP, POMC, MCH and Hypocretin/Orexin in the Rat Hypothalamus. Neuroreport 17-1-2000; 11: 117–121.

    Article  Google Scholar 

  19. Miselis RR, Epstein AN . Feeding Induced by Intracerebroventricular 2-Deoxy-D-Glucose in the Rat. Am J Physiol 1975; 229: 1438–1447.

    Article  CAS  PubMed  Google Scholar 

  20. Thompson DA, Campbell RG . Hunger in humans induced by 2-Deoxy-D-Glucose: glucoprivic control of taste preference and food intake. Science 1977; 198: 1065–1068.

    Article  CAS  PubMed  Google Scholar 

  21. Proescholdt MA, Jacobson S, Tresser N, Oldfield EH, Merrill MJ . Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats. J Neuropathol Exp Neurol 2002; 61: 914–925.

    Article  CAS  PubMed  Google Scholar 

  22. Schwartz MW, Woods SC, Porte Jr D, Seeley RJ, Baskin DG . Central nervous system control of food intake. Nature 2000; 404: 661–671.

    CAS  PubMed  Google Scholar 

  23. Gielkens HA, Verkijk M, Lam WF, Lamers CB, Masclee AA . Effects of hyperglycemia and hyperinsulinemia on satiety in humans. Metabolism 1998; 47: 321–324.

    Article  CAS  PubMed  Google Scholar 

  24. Mayer J, Thomas DW . Regulation of food intake and obesity. Science 1967; 156: 328–337.

    Article  CAS  PubMed  Google Scholar 

  25. Gold PW, Chrousos GP . Organization of the stress system and its dysregulation in melancholic and atypical depression: High Vs Low CRH/NE States. Mol Psychiatry 2002; 7: 254–275.

    Article  CAS  PubMed  Google Scholar 

  26. Arase K, York DA, Shimizu H, Shargill N, Bray GA . Effects of corticotropin-releasing factor on food intake and brown adipose tissue thermogenesis in rats. Am J Physiol 1988; 255 (3 Pt 1): E255–E259.

    CAS  PubMed  Google Scholar 

  27. Hamilton CL, Lewis D . Feeding behavior in monkeys with spontaneous diabetes mellitus. J Med Primatol 1975; 4: 145–153.

    Article  CAS  PubMed  Google Scholar 

  28. Ferrara N, Henzel WJ . Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 1989; 161: 851–858.

    Article  CAS  PubMed  Google Scholar 

  29. Gaillard I, Keramidas M, Liakos P, Vilgrain I, Feige JJ, Vittet D . ACTH-regulated expression of vascular endothelial growth factor in the adult bovine adrenal cortex: a possible role in the maintenance of the microvasculature. J Cell Physiol 2000; 185: 226–234.

    Article  CAS  PubMed  Google Scholar 

  30. Jakeman LB, Winer J, Bennett GL, Altar CA, Ferrara N . Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. J Clin Invest 1992; 89: 244–253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Leybaert L . Neurobarrier coupling in the brain: a partner of neurovascular and neurometabolic coupling? J Cereb Blood Flow Metab 2005; 25: 2–16.

    Article  CAS  PubMed  Google Scholar 

  32. Aiello LP, Pierce EA, Foley ED, Takagi H, Chen H, Riddle L et al. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci USA 1995; 92: 10457–10461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. De Vriese AS, Tilton RG, Elger M, Stephan CC, Kriz W, Lameire NH . Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. J Am Soc Nephrol 2001; 12: 993–1000.

    CAS  Google Scholar 

  34. Rivard A, Silver M, Chen D, Kearney M, Magner M, Annex B et al. Rescue of diabetes-related impairment of angiogenesis by intramuscular gene therapy with Adeno-VEGF. Am J Pathol 1999; 154: 355–363.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Schratzberger P, Walter DH, Rittig K, Bahlmann FH, Pola R, Curry C et al. Reversal of experimental diabetic neuropathy by VEGF gene transfer. J Clin Invest 2001; 107: 1083–1092.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Dr Aja Marxsen, Oliver Korn, Stefan Sopke and Christina Blum for their expert assistance and invaluable work.

Author information

Author notes

  1. C Hubold and K M Oltmanns: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine I, University of Luebeck, Luebeck, Germany

    C Hubold, B Schultes, H L Fehm & A Peters

  2. Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany

    K M Oltmanns & U Schweiger

  3. Department of Neuroendocrinology, University of Luebeck, Luebeck, Germany

    K M Oltmanns & J Born

  4. Department of Physiology, University of Luebeck, Luebeck, Germany

    W Jelkmann

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  1. C Hubold
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  2. K M Oltmanns
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  5. J Born
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  6. H L Fehm
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  7. U Schweiger
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  8. A Peters
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Correspondence to C Hubold.

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Hubold, C., Oltmanns, K., Schultes, B. et al. High plasma VEGF relates to low carbohydrate intake in patients with type 2 diabetes. Int J Obes 30, 1356–1361 (2006). https://doi.org/10.1038/sj.ijo.0803293

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  • DOI: https://doi.org/10.1038/sj.ijo.0803293

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