Figure 7.

Protein Succination in Renal Tubular Cells and Cardiomyocytes from Hyperglycemic Fh1βKO Mice

(A) IHC for 2SC in CTL (left) and diabetic Fh1βKO (right) hearts showing staining in a subset of cells in diabetic animals but not in the non-diabetic CTLs. Scale bar, 50 μm.

(B) As in (A) but showing sections of kidney in CTL (left) and normoglycemic (middle) or hyperglycemic (right) Fh1βKO mice as indicated.

(C) Schematic of the proposed relationship between hyperglycemia, impaired ATP production, and protein succination. The increased intracellular fumarate resulting from reduced activity of fumarase leads to protein succination. The sites of action of SGLT inhibitors and tolbutamide are indicated.

Sections in (A) and (B) are representative of observations in >10 animals of both genotypes.