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. 2017 Jun 2;158(8):2486–2502. doi: 10.1210/en.2017-00111

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This article has been published under the terms of the Creative Commons Attribution License (CC BY; https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s).

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Figure 6. — Insulin and glucagon secretion from isolated Nuf mice pancreatic islets. (a) The total insulin content of Casr^Nuf/Nuf islets was not altered compared with Casr^+/+ islets. (b) Casr^+/+ and Casr^Nuf/Nuf islets were incubated in 1.6 mM [Ca²⁺]_o and exposed to varying glucose concentrations (1, 6, or 20 mM). Casr^+/+ and Casr^Nuf/Nuf islets showed significantly increased insulin secretion following stimulation with 20 mM glucose. No significant differences in the maximal insulin secretory responses were observed between Casr^+/+ and Casr^Nuf/Nuf islets. (c) The total glucagon content of Casr^Nuf/Nuf islets was significantly increased compared with Casr^+/+ islets. (d) Casr^+/+ and Casr^Nuf/Nuf islets were incubated in 1.6 mM [Ca²⁺]_o and exposed to 1 and 6 mM glucose concentrations. Casr^+/+ islets showed a significant reduction in glucagon secretion following stimulation with 6 mM glucose. In contrast, glucagon secretion from Casr^Nuf/Nuf islets failed to suppress following glucose stimulation, and Casr^Nuf/Nuf islets had significantly increased glucagon secretion compared with Casr^+/+ islets at 6 mM glucose. (e) The effect of Ca²⁺_o on insulin secretion was assessed by incubating Casr^+/+ and Casr^Nuf/Nuf islets with varying Ca²⁺_o concentrations (0.8 or 1.6 mM) and exposing them to low (1 mM) or high (20 mM) glucose. Exposure to low (0.8 mM) Ca²⁺_o suppressed insulin secretion from Casr^+/+ and Casr^Nuf/Nuf islets at 20 mM glucose. (f) Exposure to low (0.8 mM) Ca²⁺_o increased glucagon secretion from Casr^+/+ islets at 20 mM glucose but had no effect on glucagon secretion from Casr^Nuf/Nuf islets. Islet insulin and glucagon in panels (a–d) were measured by radioimmunoassay and by duplex rat/mouse ELISA (Meso Scale Discovery) in panels (e) and (f). The sample size (N) represents batches of size-matched islets, which were pooled from three to six Casr^+/+ mice and six Casr^Nuf/Nuf mice. Mean ± standard error of the mean values for the respective groups are indicated by solid bars. *P < 0.05, **P < 0.01, ***P < 0.001. NS, nonsignificant.