Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Novel GLP-1 mimetics developed to treat type 2 diabetes promote progenitor cell proliferation in the brain
AU - Hamilton, A.
AU - Patterson, S.
AU - Porter, David
AU - Gault, Victor A.
AU - Hölscher, Christian
N1 - Copyright © 2011 Wiley-Liss, Inc.
PY - 2011/4
Y1 - 2011/4
N2 - One of the symptoms of diabetes is the progressive development of neuropathies. One mechanism to replace neurons in the CNS is through the activation of stem cells and neuronal progenitor cells. We have tested the effects of the novel GLP-1 mimetics exenatide (exendin-4; Byetta) and liraglutide (NN2211; Victoza), which are already on the market as treatments for type 2 diabetes, on the proliferation rate of progenitor cells and differentiation into neurons in the dentate gyrus of brains of mouse models of diabetes. GLP-1 analogues were injected subcutaneously for 4, 6, or 10 weeks once daily in three mouse models of diabetes: ob/ob mice, db/db mice, or high-fat-diet-fed mice. Twenty-four hours before perfusion, animals were injected with 5'-bromo-2'-deoxyuridine (BrdU) to mark dividing progenitor cells. By using immunohistochemistry and stereological methods, the number of progenitor cells or doublecortin-positive young neurons in the dentate gyrus was estimated. We found that, in all three mouse models, progenitor cell division was enhanced compared with nondiabetic controls after chronic i.p. injection of either liraglutide or exendin-4 by 100-150% (P
AB - One of the symptoms of diabetes is the progressive development of neuropathies. One mechanism to replace neurons in the CNS is through the activation of stem cells and neuronal progenitor cells. We have tested the effects of the novel GLP-1 mimetics exenatide (exendin-4; Byetta) and liraglutide (NN2211; Victoza), which are already on the market as treatments for type 2 diabetes, on the proliferation rate of progenitor cells and differentiation into neurons in the dentate gyrus of brains of mouse models of diabetes. GLP-1 analogues were injected subcutaneously for 4, 6, or 10 weeks once daily in three mouse models of diabetes: ob/ob mice, db/db mice, or high-fat-diet-fed mice. Twenty-four hours before perfusion, animals were injected with 5'-bromo-2'-deoxyuridine (BrdU) to mark dividing progenitor cells. By using immunohistochemistry and stereological methods, the number of progenitor cells or doublecortin-positive young neurons in the dentate gyrus was estimated. We found that, in all three mouse models, progenitor cell division was enhanced compared with nondiabetic controls after chronic i.p. injection of either liraglutide or exendin-4 by 100-150% (P
KW - Animals
KW - Brain
KW - Cell Differentiation
KW - Cell Proliferation
KW - Dentate Gyrus
KW - Diabetes Mellitus, Type 2
KW - Disease Models, Animal
KW - Glucagon-Like Peptide 1
KW - Hypoglycemic Agents
KW - Immunohistochemistry
KW - Male
KW - Mice
KW - Neural Stem Cells
KW - Neurogenesis
KW - Neurons
KW - Peptides
KW - Venoms
U2 - 10.1002/jnr.22565
DO - 10.1002/jnr.22565
M3 - Journal article
C2 - 21312223
VL - 89
SP - 481
EP - 489
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
SN - 0360-4012
IS - 4
ER -