T2D human islets have impaired insulin secretion and oxygen consumption and different glucose-mediated glucagon suppression and GABA shunt.
A shows insulin secretion in response to glucose in the presence of 4.0 mm AAM in normal (filled circles with black line; n = 5) and T2D islets (T2D-αGR, open circles with dashed gray line; T2D-αNGR, triangles with dashed black line; n = 3 for each). Versus T2D-αNGR and normal, * indicates p < 0.05; versus T2D-αGR and normal, # indicates p < 0.05; 25 mm glucose versus 0 mm glucose, a indicates p < 0.05; 25 mm glucose versus 5 mm glucose, b indicates p < 0.05. B shows glucagon secretion (inset shows the percent changes). Versus T2D-αNGR and normal, * indicates p < 0.05; versus 0 mm glucose, a indicates p < 0.05. C shows the glucose stimulation of islet oxygen consumption in normal and T2D islets (normal, black-filled bars (n = 5); T2D-αGR, gray-filled bars; T2D-αNGR, open bars (n = 3 for each); also shown in D and E). Versus 0 mm glucose (G, 0), a indicates p < 0.01; versus 25 mm glucose (G, 25), b indicates p < 0.01; versus normal, * indicates p < 0.05. D shows GABA/glutamate ratios. Versus normal, * indicates p < 0.05; versus 0 mm glucose, a indicates p < 0.05. E shows expression data for selected genes detected by quantitative PCR. Versus normal, * indicates p < 0.05. Data are presented as mean ± S.E. (error bars). GK, glucokinase; PC, pyruvate carboxylase; GDH, glutamate dehydrogenase; FCCP, carbonyl cyanide p-trifluoromethoxyphenylhydrazone.