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. Author manuscript; available in PMC: 2019 Jan 9.
Published in final edited form as: Cell Metab. 2017 Nov 2;27(1):218–225.e4. doi: 10.1016/j.cmet.2017.10.002

Figure 4. Artemether abrogates beta cell calcium responses and insulin secretion.

Figure 4

(A) The calcium responses of freshly isolated islets from Ins1-H2B-Chy x Ucn3-Cre x Rosa26-stop-GCaMP6 triple transgenic mice were imaged in 3D during a standard glucose stimulation protocol from 5.5 to 16.8 to 5.5 mM glucose, followed by a brief depolarization by 30 mM KCl to demonstrate responsiveness of the islets throughout the experiment. Each trace represents the combined response of a single islet. Thumbnails provide snapshots of the calcium response at key points during the trace for 2 of the 5 islets imaged. See also Movie S3.

(B) Islets from the same animal and subjected to the same stimulation protocol as in (A), but after 72 hr in culture. First phase secretion is intact, but the second phase is muted and pulsatility is lost.

(C) Islets from the same animal and subjected to the same stimulation protocol as in (A), but after 72 hr in culture in the presence of 10 μM artemether. The glucose response is completely abolished and only a modest response to forced depolarization with 30 mM KCl can be detected.

(D) Insulin secretion from freshly isolated mouse islets in response to glucose, glucose + Exendin 4, or 30 mM KCl (n=4 replicate treatments). *p<0.05, **p<0.01 compared to 5.5 mM glucose. (E) Insulin secretion on islets from the same batch as in (D), but after 72 hr in culture (n=4 replicate treatments). *p<0.05, **p<0.01 compared to 5.5 mM glucose.

(F) Insulin secretion on islets from the same batch as in (D), but after 72 hr of treatment with 10 μM artemether (n=4 replicate treatments). *p<0.05, **p<0.01 compared to 5.5 mM glucose.

(G) Insulin secretion from freshly isolated human islets in response to glucose or 30 mM KCl (n=8 replicate treatments). *p<0.05, **p<0.01, ***p<0.001 compared to 5.5 mM glucose.

(H) Insulin secretion on islets from the same batch as in (G), but after 72 hr in culture (n=6 replicate treatments). *p<0.05, **p<0.01, ***p<0.001 compared to 5.5 mM glucose.

(I) Insulin secretion on islets from the same batch as in (G), but after 72 hr of treatment with 10 μM artemether (n=6 replicate treatments). *p<0.05, **p<0.001, ***p<0.001 compared to 5.5 mM glucose.