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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.

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Kalsbeek MJ, Wolff SE, Korpel NL, la Fleur SE, Romijn JA, Fliers E et al. The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia. JCI insight. 2020 Aug 20;5(16):e133868. doi: 10.1172/jci.insight.133868

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Kalsbeek, Martin Jt ; Wolff, Samantha Ec ; Korpel, Nikita L. et al. / The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia. In: JCI insight. 2020 ; Vol. 5, No. 16.

BibTeX

@article{0bf327f33fac44e4b8073526edb4b31a,
title = "The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia",
abstract = "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.",
keywords = "Diabetes, Endocrinology, Insulin, NPY, Neuroscience",
author = "Kalsbeek, {Martin Jt} and Wolff, {Samantha Ec} and Korpel, {Nikita L.} and {la Fleur}, {Susanne E.} and Romijn, {Johannes A.} and Eric Fliers and Andries Kalsbeek and Swaab, {Dick F.} and Inge Huitinga and Hol, {Elly M.} and Chun-Xia Yi",
year = "2020",
month = aug,
day = "20",
doi = "10.1172/jci.insight.133868",
language = "English",
volume = "5",
journal = "JCI insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "16",

}

RIS

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