Figure 7.
Disruption of Hubs by Pro-Inflammatory and Glucolipotoxic Insults
(A and B) IL-1β/IL-6 and IL-1β/TNF-α reduce hub number after 2 hr (n = 6 islets from three animals).
(C and D) Cytokine (Cyto; IL-1β/IL-6) decreases hub number in real-time (n = 8 from four animals).
(E and F) Cytokine alters the distribution of correlated links and power law scaling exponent (k) value, indicating a decreased number of cells in the high connectivity (i.e., hub) range (n = 8 from four animals) (R2 = 0.38–0.74). The power law was log-log transformed to a linear relationship to better demonstrate the distribution.
(G) Cytokine (IL-1β/IL-6) exposure dramatically reduces the proportion of correlated links.
(H to I) Application of IL-1β/IL-6 or IL-1β/TNF-α for 2 hr (H) or 4 hr (I) is not cytotoxic (n = 21 islets per condition from 6 animals) (scale bar, 25 μm).
(J) 2 hr application of IL-1β/IL-6 or IL-1β/TNF-α does not induce apoptosis (n = 18–20 islets from five animals).
(K and L) IL-1β/IL-6 and IL-1β/TNF-α decrease connexin-36 (Gjd2) mRNA levels (n = 10 animals).
(M) IL-1β/IL-6 and IL-1β/TNF-α reduce the number of immunostained gap junction (connexin-36; Cx36) plaques (n = 9–12 islets from six animals) (scale bar, 12.5 μm).
(N) Glucotoxicity (Glucotox) and glucolipotoxicity (Glucolipotox) reduce the proportion of hubs and correlated links in mouse islets (n = 6 animals).
(O) As for (N), but showing effects of glucolipotoxicity-alone on human islets (n = 5 donors).
Control, Con (buffer-alone). Data are means ± SEM. ∗p < 0.05; ∗∗p < 0.01. NS, non-significant. See also Figure S6.