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

ABSTRACT: Current treatments for type 1 diabetes (T1D) focus on optimizing insulin replacement. We demonstrate the therapeutic potential of the large secreted protein fraction from brown adipose tissue (BAT), independent of insulin. This secreted fraction mediates insulin receptor-dependent recovery of euglycemia in diabetic nonobese diabetic (NOD) mice by suppressing glucagon secretion. It also promotes white adipocyte differentiation and browning, and enhances glucose uptake in adipose tissue, skeletal muscle, and liver. From this fraction, we identify nidogen-2 as a brown adipocyte-secreted factor that reverses hyperglycemia in T1D NOD, inhibits glucagon secretion from pancreatic α-cells, and mimics other actions of the secreted fraction. These findings provide proof of principle that the pleiotropic effects of BAT-derived peptides represent a novel approach to diabetes management.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brown Adipose Tissue

DISEASE(S): Type 1 Diabetes Mellitus

SUBMITTER: Dennis Goldfarb

LAB HEAD: David Piston

PROVIDER: PXD051972 | Pride | 2025-03-13

REPOSITORIES: Pride

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			Action	DRS
	DIA-NN_results.zip	Other
	PI018_SECFraction_EWZ_43_DIA.raw	Raw
	PI019_SECFraction_EWZ_44_DIA.raw	Raw
	PI020_SECFraction_EWZ_45_DIA.raw	Raw
	PI021_SECFraction_EWZ_46_DIA.raw	Raw

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