Fig. 4.

Human β-cell proliferation is induced by treatment with some, but not all, compounds tested. A: treatment of human islet cells with harmine at 1 and 10 μM in 5 or 11 mM glucose increased β-cell proliferation. **P < 0.01, 5 mM glucose control vs. 1 μM harmine or 10 μM harmine. *P < 0.01, 5 mM glucose control vs. 1 μM harmine or 10 μM harmine. B and C: neurotransmitters GABA (B) and serotonin (C) had a limited effect on β-cell proliferation, and only treatment with 100 μM GABA at 5 mM glucose was statistically significant *P < 0.05, 5 mM glucose control vs. 100 μM GABA. D–F: compounds involved in adenosine signaling and metabolism [NECA (D), UK-432097 (E), and A-134974 (F)] had a modest effect, with 1 μM UK-432097 and 10 μM A-134974 at 11 mM glucose causing a small but statistically significant increase in β-cell proliferation. *P < 0.05, 11 mM glucose control vs. 1 μM UK-432097 and control vs. 10 μM A-134974. G–J: hormones prolactin (G), PDGF (H), erythropoietin (I), and exendin-4 (J) had no effect on β-cell proliferation other than 1,250 ng/ml PDGF at 5 mM glucose, which caused a small but significant increase in proliferation. *P < 0.05, 5 mM glucose control vs. 1,250 ng/ml PDGF. K and L: treatment with members of the TGF-β superfamily myostatin (K) and activin A (L) had no significant effect on β-cell proliferation. Comparisons between controls or compound treatments at 5 vs. 11 mM glucose were not statistically significant in any compound or control tested, and there was no difference between vehicle controls (P = 0.13–0.62); n = 3–6 donors/treatment condition.