Liver-derived Neuregulin1α stimulates compensatory pancreatic β cell hyperplasia in insulin resistance.
Nature communications – March 13, 2025
Source: PubMed
Summary
A liver protein called Neuregulin1α plays a vital role in enhancing pancreatic β cell growth, especially during insulin resistance. In studies with mice, higher levels of this protein helped maintain insulin production, while its absence led to impaired glucose management. This discovery highlights Neuregulin1α's potential in addressing type 2 diabetes.
Abstract
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.