Linagliptin treatment improves cerebrovascular function and remodeling and restores reduced cerebral perfusion in Type 2 diabetes

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volumn 311, Issue 3, 2016, Pages R466-R477

  Hardigan, Trevor ^b   Yasir, Abdul ^b   Abdelsaid, Mohammed ^a,b   Coucha, Maha ^a,b   El Shaffey, Sally ^b   Li, Weiguo ^a,b   Johnson, Maribeth H ^c   Ergul, Adviye ^a,b  

^a VETERANS AFFAIRS MEDICAL CENTER   (United States)

^b MEDICAL COLLEGE OF GEORGIA   (United States)

^c AUGUSTA UNIVERSITY   (United States)

Author keywords

Cerebrovascular; Cognitive impairment; Diabetes; Dipeptidyl peptidase 4; Linagliptin

Indexed keywords

DIPEPTIDYL PEPTIDASE IV; GLUCOSE; INSULIN; LINAGLIPTIN; ANTIDIABETIC AGENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN ANGIOGRAPHY; BRAIN PERFUSION; CEREBROVASCULAR DISEASE; CONTROLLED STUDY; DOSE RESPONSE; ENZYME ACTIVITY; ENZYME BLOOD LEVEL; ENZYME INHIBITION; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; HIPPOCAMPUS; INSULIN BLOOD LEVEL; LASER DOPPLER FLOWMETRY; MALE; MIDDLE CEREBRAL ARTERY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NOVEL OBJECT RECOGNITION TEST; PRIORITY JOURNAL; RAT; REPEATED DRUG DOSE; VASCULAR REMODELING; VASODILATATION; ANIMAL; BLOOD FLOW VELOCITY; BRAIN CIRCULATION; CEREBROVASCULAR DISORDERS; COGNITION; COMPLICATION; DIABETES MELLITUS, TYPE 2; DRUG EFFECTS; PATHOPHYSIOLOGY; TREATMENT OUTCOME;

ANIMALS; BLOOD FLOW VELOCITY; CEREBROVASCULAR CIRCULATION; CEREBROVASCULAR DISORDERS; COGNITION; DIABETES MELLITUS, TYPE 2; DOSE-RESPONSE RELATIONSHIP, DRUG; HYPOGLYCEMIC AGENTS; LINAGLIPTIN; MALE; RATS; TREATMENT OUTCOME; VASCULAR REMODELING;

EID: 84986550362     PISSN: 03636119     EISSN: 15221490     Source Type: Journal    
DOI: 10.1152/ajpregu.00057.2016     Document Type: Article

References (50)

1. Abdelsaid M, Kaczmarek J, Coucha M, Ergul A. Dual endothelin receptor antagonism with bosentan reverses established vascular remodeling and dysfunctional angiogenesis in diabetic rats: relevance to glycemic control. Life Sci 118: 268-273, 2014.
2. Abdelsaid M, Ma H, Coucha M, Ergul A. Late dual endothelin receptor blockade with bosentan restores impaired cerebrovascular function in diabetes. Life Sci 118: 263-267, 2014.
3. Albasser MM, Chapman RJ, Amin E, Iordanova MD, Vann SD, Aggleton JP. New behavioral protocols to extend our knowledge of rodent object recognition memory. Learn Mem 17: 407-419, 2010.
4. American Diabetes Association. National Diabetes Fact Sheet [Online]. http://www.diabetes.org/diabetes-basics/statistics/.
5. Cipolla M, McCall A, Lessov N, Porter J. Reperfusion decreases myogenic reactivity and alters middle cerebral artery function after focal cerebral ischemia in rats. Stroke 28: 176-80, 1997.
6. Coucha M, Li W, Johnson MH, Fagan SC, Ergul A. Protein nitration impairs the myogenic tone of rat middle cerebral arteries in both ischemic and nonischemic hemispheres after ischemic stroke. Am J Physiol Heart Circ Physiol 305: H1726-H1735, 2013.
7. Darsalia V, Larsson M, Lietzau G, Nathanson D, Science C, Institutet K. Gliptins-mediated neuroprotection against stroke requires chronic pretreatment and is glucagon-like peptide-1 receptor independent. Diabetes Obes Metab 18: 537-541, 2016.
8. Darsalia V, Ortsäter H, Olverling A, Darlöf E, Wolbert P, Nyström T, Klein T, Sjöholm Å, Patrone C. The DPP-4 inhibitor linagliptin counteracts stroke in the normal and diabetic mouse brain: A comparison with glimepiride. Diabetes 62: 1289-1296, 2013.
9. Davis MJ, Hill MA. Signaling mechanisms underlying the vascular myogenic response. Physiol Rev 79: 387-423, 1999.
10. Dokken BB, Piermarini CV, Teachey MK, Gura MT, Dameff CJ, Heller BD, Krate J, Ashgar AM, Querin L, Mitchell JL, Hilwig RW, Kern KB. Glucagon-like peptide-1 preserves coronary microvascular endothelial function after cardiac arrest and resuscitation: potential antioxidant effects. Am J Physiol Heart Circ Physiol 304: H538-H546, 2013.
11. Doupis J. Linagliptin: From bench to bedside. Drug Des Devel Ther 8: 431-446, 2014.
12. Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF. Glucagonlike peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci USA 84: 3434-3438, 1987.
13. Erdös B, Snipes JA, Miller AW, Busija DW. Cerebrovascular dysfunction in Zucker obese rats is mediated by oxidative stress and protein kinase C. Diabetes 53: 1352-1359, 2004.
14. Ergul A, Abdelsaid M, Fouda AY, Fagan SC. Cerebral neovascularization in diabetes: implications for stroke recovery and beyond. J Cereb Blood Flow Metab 34: 553-563, 2014.
15. Ergul A, Kelly-Cobbs A, Abdalla M, Fagan SC. Cerebrovascular complications of diabetes: focus on stroke. Endocr Metab Immune Disord Drug Targets 12: 148-158, 2012.
16. Ergul A, Li W, Elgebaly MM, Bruno A, Fagan SC. Hyperglycemia, diabetes and stroke: Focus on the cerebrovasculature. Vascul Pharmacol 51: 44-49, 2009.
17. Faraci F, Heistad D. Regulation of the cerebral circulation: role of endothelium and potassium channels. Physiol Rev 78: 53-97, 1998.
18. Faraci FM, Heistad DD. Regulation of large cerebral arteries and cerebral microvascular pressure. Circ Res 66: 8-17, 1990.
19. Ferreira L, Teixeira-de-Lemos E, Pinto F., Parada B, Mega C, Vala H, Pinto R, Garrido P, Sereno J, Fernandes R, Santos P, Velada I, Melo A, Nunes S, Teixeira F, Reis F. Effects of sitagliptin tTreatment on dysmetabolism, inflammation, and oxidative stress in an animal model of Type 2 diabetes (ZDF rat). Mediators Inflamm 2010: 1-11, 2010.
20. Gault VA, Lennox R, Flatt PR. Sitagliptin, a dipeptidyl peptidase-4 inhibitor, improves recognition memory, oxidative stress and hippocampal neurogenesis and upregulates key genes involved in cognitive decline. Diabetes Obes Metab 17: 403-413, 2015.
21. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Heart Disease and Stroke Statistics—2014 Update: A Report From the American Heart Association. Circulation 129: e28-e292, 2014.
22. Harris AK, Hutchinson JR, Sachidanandam Kamakshi Johnson MH, Dorrance AM, Stepp DW, Fagan SC, Ergul A. Type 2 diabetes causes remodeling of cerebrovasculature via differential regulation of matrix metalloproteinases and collagen synthesis role of endothelin-1 [Online]. Diabetes 54: 2638-2644, 2005.
23. Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci 5: 347-360, 2004.
24. Iadecola C. The pathobiology of vascular dementia. Neuron 80: 844-866, 2013.
25. Kalani M. The importance of endothelin-1 for microvascular dysfunction in diabetes. Vasc Health Risk Manag 4: 1061-1068, 2008.
26. Katakam PVG, Domoki F, Lenti L, Gáspár T, Institoris A, Snipes JA, Busija DW. Cerebrovascular responses to insulin in rats. J Cereb Blood Flow Metab 29: 1955-1967, 2009.
27. Katakam PVG, Snipes JA, Steed MM, Busija DW. Insulin-induced generation of reactive oxygen species and uncoupling of nitric oxide synthase underlie the cerebrovascular insulin resistance in obese rats. J Cereb Blood Flow Metab 32: 792-804, 2012.
28. Kelly-Cobbs AI, Prakash R, Coucha M, Knight a R, Li W, Ogbi SN, Johnson M, Ergul A. Cerebral myogenic reactivity and blood flow in type 2 diabetic rats: role of peroxynitrite in hypoxia-mediated loss of myogenic tone. J Pharmacol Exp Ther 342: 407-415, 2012.
29. Kelly-Cobbs A, Elgebaly M, Li W, Ergul A. Pressure-independent cerebrovascular remodelling and changes in myogenic reactivity in diabetic Goto-Kakizaki rat in response to glycaemic control. Acta Physiol 203: 245-251, 2011.
30. Kim YS, Immink RV, Stok WJ, Karemaker JM, Secher NH, van Lieshout JJ. Dynamic cerebral autoregulatory capacity is affected early in Type 2 diabetes. Clin Sci (Lond) 115: 255-262, 2008.
31. Kodl CT, Seaquist ER. Cognitive dysfunction and diabetes mellitus. Endocr Rev 29: 494-511, 2008.
32. Koibuchi N, Hasegawa Y, Katayama T, Toyama K, Uekawa K, Sueta D, Kusaka H, Ma M, Nakagawa T, Lin B, Kim-Mitsuyama S. DPP-4 inhibitor linagliptin ameliorates cardiovascular injury in salt-sensitive hypertensive rats independently of blood glucose and blood pressure. Cardiovasc Diabetol 13: 157, 2014.
33. Koliaki C, Doupis J. Incretin-based therapy: a powerful and promising weapon in the treatment of type 2 diabetes mellitus. Diabetes Ther 2: 101-121, 2011.
34. Kröller-Schön S, Knorr M, Hausding M, Oelze M, Schuff A, Schell R, Sudowe S, Scholz A, Daub S, Karbach S, Kossmann S, Gori T, Wenzel P, Schulz E, Grabbe S, Klein T, Münzel T, Daiber A. Glucoseindependent improvement of vascular dysfunction in experimental sepsis by dipeptidyl-peptidase 4 inhibition. Cardiovasc Res 96: 140-149, 2012.
35. Li W, Qu Z, Prakash R, Chung C, Ma H, Hoda N, Fagan SC, Ergul A. Comparative analysis of the neurovascular injury and functional outcomes in experimental stroke models in diabetic Goto-Kakizaki rats. Brain Res 1541: 106-114, 2013.
36. Ma M, Hasegawa Y, Koibuchi N, Toyama K, Uekawa K, Nakagawa T, Lin B, Kim-Mitsuyama S. DPP-4 inhibition with linagliptin ameliorates cognitive impairment and brain atrophy induced by transient cerebral ischemia in type 2 diabetic mice. Cardiovasc Diabetol 14: 54, 2015.
37. Matsubara J, Sugiyama S, Sugamura K, Nakamura T, Fujiwara Y, Akiyama E, Kurokawa H, Nozaki T, Ohba K, Konishi M, Maeda H, Izumiya Y, Kaikita K, Sumida H, Jinnouchi H, Matsui K, Kim-Mitsuyama S, Takeya M, Ogawa H. A dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin, improves endothelial function and reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice. J Am Coll Cardiol 59: 265-76, 2012.
38. Owens WB. Blood pressure control in acute cerebrovascular disease. J Clin Hypertens 13: 205-211, 2011.
39. Palomares SM, Gardner-Morse I, Sweet JG, Cipolla MJ. Peroxynitrite decomposition with FeTMPyP improves plasma-induced vascular dysfunction and infarction during mild but not severe hyperglycemic stroke. J Cereb Blood Flow Metab 32: 1035-1045, 2012.
40. Palomares SM, Cipolla M J. Vascular protection following cerebral ischemia and reperfusion. J Neurol Neurophysiol 01: 1-12, 2011.
41. Paulson O, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev 2: 161-92, 1990.
42. Peterson EC, Wang Z, Britz G. Regulation of cerebral blood flow. Int J Vasc Med 2011: 1-8, 2011.
43. Phillips SA, Sylvester FA, Frisbee JC. Oxidant stress and constrictor reactivity impair cerebral artery dilation in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 288: R522-R530, 2005.
44. Polonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest 81: 442-448, 1988.
45. Prakash R, Li W, Qu Z, Johnson a M., Fagan SC, Ergul A. Vascularization pattern after ischemic stroke is different in control versus diabetic rats relevance to stroke recovery. Stroke 44: 2875-2882, 2013.
46. Sachidanandam K, Hutchinson JR, Elgebaly MM, Mezzetti EM, Dorrance AM, Motamed K, Ergul A. Glycemic control prevents microvascular remodeling and increased tone in type 2 diabetes: link to endothelin-1. Am J Physiol Regul Integr Comp Physiol 296: R952-R959, 2009.
47. Schuit F, Huypens P, Heimberg H, Pipeleers D. Glucose sensing in pancreatic β-cells [Online]. Diabetes 50: 1-11, 2001. http://diabetes.diabetesjournals.org/content/50/1/1.short.
48. Shah Z, Pineda C, Kampfrath T, Maiseyeu A, Ying Z, Racoma I, Deiuliis J, Xu X, Sun Q, Moffatt-Bruce S, Villamena F, Rajagopalan S. Acute DPP-4 inhibition modulates vascular tone through GLP-1 independent pathways. Vascul Pharmacol 55: 2-9, 2011.
49. Takasawa W, Ohnuma K, Hatano R, Endo Y, Dang NH, Morimoto C. Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines. Biochem Biophys Res Commun 401: 7-12, 2010.
50. Zhong J, Rao X, Rajagopalan S. An emerging role of dipeptidyl peptidase 4 (DPP4) beyond glucose control: Potential implications in cardiovascular disease. Atherosclerosis 226: 305-314, 2013.