Research output: Contribution to journal › Article › Academic › peer-review
The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia. / Kalsbeek, Martin Jt; Wolff, Samantha Ec; Korpel, Nikita L. et al.
In: JCI insight, Vol. 5, No. 16, e133868, 20.08.2020.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia
AU - Kalsbeek, Martin Jt
AU - Wolff, Samantha Ec
AU - Korpel, Nikita L.
AU - la Fleur, Susanne E.
AU - Romijn, Johannes A.
AU - Fliers, Eric
AU - Kalsbeek, Andries
AU - Swaab, Dick F.
AU - Huitinga, Inge
AU - Hol, Elly M.
AU - Yi, Chun-Xia
PY - 2020/8/20
Y1 - 2020/8/20
N2 - Animal studies indicate that hypothalamic dysfunction plays a major role in type 2 diabetes mellitus (T2DM) development, and that insulin resistance and inflammation are important mechanisms involved in this disorder. However, it remains unclear how T2DM and antidiabetic treatments affect the human hypothalamus. Here, we characterized the proopiomelanocortin (POMC) immunoreactive (-ir) neurons, the neuropeptide-Y-ir (NPY-ir) neurons, the ionized calcium-binding adapter molecule 1-ir (iba1-ir) microglia, and the transmembrane protein 119-ir (TMEM119-ir) microglia in the infundibular nucleus (IFN) of human postmortem hypothalamus of 32 T2DM subjects with different antidiabetic treatments and 17 matched nondiabetic control subjects. Compared with matched control subjects, T2DM subjects showed a decrease in the number of POMC-ir neurons, but no changes in NPY-ir neurons or microglia. Interestingly, T2DM subjects treated with the antidiabetic drug metformin had fewer NPY-ir neurons and microglia than T2DM subjects not treated with metformin. We found that the number of microglia correlated with the number of NPY-ir neurons, but only in T2DM subjects. These results indicate that different changes in POMC and NPY neurons and microglial cells in the IFN accompany T2DM. In addition, T2DM treatment modality is associated with highly selective changes in hypothalamic neurons and microglial cells.
AB - Animal studies indicate that hypothalamic dysfunction plays a major role in type 2 diabetes mellitus (T2DM) development, and that insulin resistance and inflammation are important mechanisms involved in this disorder. However, it remains unclear how T2DM and antidiabetic treatments affect the human hypothalamus. Here, we characterized the proopiomelanocortin (POMC) immunoreactive (-ir) neurons, the neuropeptide-Y-ir (NPY-ir) neurons, the ionized calcium-binding adapter molecule 1-ir (iba1-ir) microglia, and the transmembrane protein 119-ir (TMEM119-ir) microglia in the infundibular nucleus (IFN) of human postmortem hypothalamus of 32 T2DM subjects with different antidiabetic treatments and 17 matched nondiabetic control subjects. Compared with matched control subjects, T2DM subjects showed a decrease in the number of POMC-ir neurons, but no changes in NPY-ir neurons or microglia. Interestingly, T2DM subjects treated with the antidiabetic drug metformin had fewer NPY-ir neurons and microglia than T2DM subjects not treated with metformin. We found that the number of microglia correlated with the number of NPY-ir neurons, but only in T2DM subjects. These results indicate that different changes in POMC and NPY neurons and microglial cells in the IFN accompany T2DM. In addition, T2DM treatment modality is associated with highly selective changes in hypothalamic neurons and microglial cells.
KW - Diabetes
KW - Endocrinology
KW - Insulin
KW - NPY
KW - Neuroscience
UR - http://www.scopus.com/inward/record.url?scp=85089714555&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.133868
DO - 10.1172/jci.insight.133868
M3 - Article
C2 - 32814716
VL - 5
JO - JCI insight
JF - JCI insight
SN - 2379-3708
IS - 16
M1 - e133868
ER -
ID: 13016570