The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia
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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical investigation
2020-08-01
|
| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.133868 |
| _version_ | 1818614088537735168 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Martin J.T. Kalsbeek |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T16:12:27Z |
| format | Article |
| id | doaj.art-b9de5be741634b388701ff71860ba83b |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-16T16:12:27Z |
| publishDate | 2020-08-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-b9de5be741634b388701ff71860ba83b2022-12-21T22:25:11ZengAmerican Society for Clinical investigationJCI Insight2379-37082020-08-01516The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microgliaMartin J.T. KalsbeekSamantha E.C. WolffNikita L. KorpelSusanne E. la FleurJohannes A. RomijnEric FliersAndries KalsbeekDick F. SwaabInge HuitingaElly M. HolChun-Xia YiAnimal 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.https://doi.org/10.1172/jci.insight.133868EndocrinologyNeuroscience |
| spellingShingle | 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 The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia JCI Insight Endocrinology Neuroscience |
| title | The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia |
| title_full | The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia |
| title_fullStr | The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia |
| title_full_unstemmed | The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia |
| title_short | The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia |
| title_sort | impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia |
| topic | Endocrinology Neuroscience |
| url | https://doi.org/10.1172/jci.insight.133868 |
| work_keys_str_mv | AT martinjtkalsbeek theimpactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT samanthaecwolff theimpactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT nikitalkorpel theimpactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT susanneelafleur theimpactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT johannesaromijn theimpactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT ericfliers theimpactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT andrieskalsbeek theimpactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT dickfswaab theimpactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT ingehuitinga theimpactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT ellymhol theimpactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT chunxiayi theimpactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT martinjtkalsbeek impactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT samanthaecwolff impactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT nikitalkorpel impactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT susanneelafleur impactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT johannesaromijn impactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT ericfliers impactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT andrieskalsbeek impactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT dickfswaab impactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT ingehuitinga impactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT ellymhol impactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia AT chunxiayi impactofantidiabetictreatmentonhumanhypothalamicinfundibularneuronsandmicroglia |