Regulation of Type 1 Diabetes via Brown Adipocyte–Secreted Proteins and the Novel Glucagon Regulator Nidogen-2

Large embryonic brown adipose tissue-secreted proteins (CB-100) suppress glucagon and normalize glycemia in mice with type 1 diabetes (T1D) without changing insulin. CB-100 prevented T1D-induced whitening, promoted browning of adipose tissue, and enhanced glucose uptake via an insulin receptor-dependent pathway. Within CB-100, nidogen-2 regulated glucagon secretion and restored euglycemia in T1D. Nidogen-2 and CB-100 unveil a therapeutic strategy for diabetes management beyond insulin-centric paradigms by modulating glucagon secretion and enhancing glucose metabolism.