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Usage Information

The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia
Martin J.T. Kalsbeek, Samantha E.C. Wolff, Nikita L. Korpel, Susanne E. la Fleur, Johannes A. Romijn, Eric Fliers, Andries Kalsbeek, Dick F. Swaab, Inge Huitinga, Elly M. Hol, Chun-Xia Yi
Martin J.T. Kalsbeek, Samantha E.C. Wolff, Nikita L. Korpel, Susanne E. la Fleur, Johannes A. Romijn, Eric Fliers, Andries Kalsbeek, Dick F. Swaab, Inge Huitinga, Elly M. Hol, Chun-Xia Yi
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Research Article Endocrinology Neuroscience

The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia

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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.

Authors

Martin J.T. Kalsbeek, Samantha E.C. Wolff, Nikita L. Korpel, Susanne E. la Fleur, Johannes A. Romijn, Eric Fliers, Andries Kalsbeek, Dick F. Swaab, Inge Huitinga, Elly M. Hol, Chun-Xia Yi

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Usage data is cumulative from February 2025 through February 2026.

Usage JCI PMC
Text version 897 80
PDF 168 15
Figure 265 0
Table 30 0
Supplemental data 60 1
Citation downloads 208 0
Totals 1,628 96
Total Views 1,724
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