The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia
| Autor: | Johannes A. Romijn, Eric Fliers, Andries Kalsbeek, Nikita L. Korpel, Elly M. Hol, Dick F. Swaab, Susanne E. la Fleur, Inge Huitinga, Samantha E C Wolff, Chun-Xia Yi, Martin J. T. Kalsbeek |
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| Přispěvatelé: | Netherlands Institute for Neuroscience (NIN), Endocrinology, Laboratory for Endocrinology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Gastroenterology Endocrinology Metabolism |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Pro-Opiomelanocortin endocrine system diseases medicine.medical_treatment 0302 clinical medicine Endocrinology Medicine Insulin Neuropeptide Y Aged 80 and over Neurons Microglia biology Diabetes General Medicine Metformin medicine.anatomical_structure Hypothalamus Pituitary Gland 030220 oncology & carcinogenesis Female Animal studies medicine.symptom Research Article medicine.drug medicine.medical_specialty Inflammation NPY 03 medical and health sciences Insulin resistance Proopiomelanocortin Internal medicine Humans Hypoglycemic Agents Aged business.industry Membrane Proteins nutritional and metabolic diseases medicine.disease 030104 developmental biology Diabetes Mellitus Type 2 nervous system Case-Control Studies biology.protein business Neuroscience |
| Zdroj: | JCI Insight, Vol 5, Iss 16 (2020) JCI insight, 5(16):133868. The American Society for Clinical Investigation JCI Insight JCI insight, 5(16):e133868. The American Society for Clinical Investigation |
| ISSN: | 2379-3708 |
| Popis: | 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. Type 2 diabetes impacts energy homeostasis-regulatory neurons and the surrounding microglia in the hypothalamus, and these effects are modulated by metformin. |
| Databáze: | OpenAIRE |
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