PMID- 32814716 OWN - NLM STAT- MEDLINE DCOM- 20210611 LR - 20210611 IS - 2379-3708 (Electronic) IS - 2379-3708 (Linking) VI - 5 IP - 16 DP - 2020 Aug 20 TI - The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia. LID - 133868 [pii] LID - 10.1172/jci.insight.133868 [doi] LID - e133868 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. FAU - Kalsbeek, Martin Jt AU - Kalsbeek MJ AD - Laboratory of Endocrinology, and. AD - Department of Endocrinology and Metabolism, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, Netherlands. AD - Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands. FAU - Wolff, Samantha Ec AU - Wolff SE AD - Laboratory of Endocrinology, and. AD - Department of Endocrinology and Metabolism, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, Netherlands. AD - Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands. FAU - Korpel, Nikita L AU - Korpel NL AD - Laboratory of Endocrinology, and. AD - Department of Endocrinology and Metabolism, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, Netherlands. AD - Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands. FAU - la Fleur, Susanne E AU - la Fleur SE AD - Laboratory of Endocrinology, and. AD - Department of Endocrinology and Metabolism, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, Netherlands. AD - Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands. FAU - Romijn, Johannes A AU - Romijn JA AD - Department of Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. FAU - Fliers, Eric AU - Fliers E AD - Department of Endocrinology and Metabolism, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, Netherlands. FAU - Kalsbeek, Andries AU - Kalsbeek A AD - Laboratory of Endocrinology, and. AD - Department of Endocrinology and Metabolism, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, Netherlands. AD - Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands. FAU - Swaab, Dick F AU - Swaab DF AD - Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands. FAU - Huitinga, Inge AU - Huitinga I AD - Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands. FAU - Hol, Elly M AU - Hol EM AD - Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, Netherlands. FAU - Yi, Chun-Xia AU - Yi CX AD - Laboratory of Endocrinology, and. AD - Department of Endocrinology and Metabolism, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, Netherlands. AD - Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200820 PL - United States TA - JCI Insight JT - JCI insight JID - 101676073 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Membrane Proteins) RN - 0 (Neuropeptide Y) RN - 0 (Tmem119 protein, human) RN - 66796-54-1 (Pro-Opiomelanocortin) RN - 9100L32L2N (Metformin) SB - IM MH - Aged MH - Aged, 80 and over MH - Case-Control Studies MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism/pathology MH - Female MH - Humans MH - Hypoglycemic Agents/*pharmacology/therapeutic use MH - Insulin/pharmacology/therapeutic use MH - Male MH - Membrane Proteins/metabolism MH - Metformin/pharmacology/therapeutic use MH - Microglia/*drug effects/metabolism/pathology MH - Neurons/drug effects/metabolism MH - Neuropeptide Y/metabolism MH - Pituitary Gland/*drug effects/metabolism MH - Pro-Opiomelanocortin/metabolism PMC - PMC7455135 OTO - NOTNLM OT - Diabetes OT - Endocrinology OT - Insulin OT - NPY OT - Neuroscience COIS- Conflict of interest: The authors have declared that no conflict of interest exists. EDAT- 2020/08/21 06:00 MHDA- 2021/06/12 06:00 PMCR- 2020/08/20 CRDT- 2020/08/21 06:00 PHST- 2019/10/01 00:00 [received] PHST- 2020/07/08 00:00 [accepted] PHST- 2020/08/21 06:00 [entrez] PHST- 2020/08/21 06:00 [pubmed] PHST- 2021/06/12 06:00 [medline] PHST- 2020/08/20 00:00 [pmc-release] AID - 133868 [pii] AID - 10.1172/jci.insight.133868 [doi] PST - epublish SO - JCI Insight. 2020 Aug 20;5(16):e133868. doi: 10.1172/jci.insight.133868.