| Journal Title /掲載ジャーナル名 |
Nature Communications |
| Publication Year and Month /掲載年月 |
March, 2025 |
| Paper Title /論文タイトル |
Liver-derived Neuregulin 1α stimulates compensatory pancreatic β cell hyperplasia in insulin resistance |
| DOI /論文DOI |
10.1038/S41467-025-57167-0 |
| Author of Waseda University /本学の著者 |
GODA, Nobuhito(Professor, Faculty of Science and Engineering, School of Advanced Science and Engineering):Correspoinding Author |
| Related Websites /関連Web |
– |
| Abstract /抄録 |
Compensatory pancreatic islet hyperplasia is an adaptive response to increased systemic insulin demand, although factors meditating this response remain poorly understood. Here, we show that a liver-derived secreted protein, Neuregulin1α, promotes compensatory proliferation of pancreatic β cells in type 2 diabetes. Liver Neuregulin1α expression and serum Neuregulin1α levels increase in male mice fed an obesity-inducing diet. Male mice lacking either Neuregulin1 in liver or its receptor, ErbB3, in β cells deteriorate systemic glucose disposal due to impaired β cell expansion with reduced insulin secretion when fed the obesity-inducing diet. Mechanistically, Neuregulin1α activates ERBB2/3-ERK signaling to stimulate β cell proliferation without altering glucose-stimulated insulin secretion potential. In patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity but without type 2 diabetes serum Neuregulin1α levels increase, while in patient with MASLD and type 2 diabetes show markedly reduced levels of Neuregulin1α. These results suggest that Neuregulin1α serves as a hepatokine that can expand functional β cell mass in type 2 diabetes. |
