<i>Tgm2</i> deletion has no effect on insulin secretion by islets.

<p>Islets were isolated (A) from 6 month-old male B6 WT and TG2^−/− (i) or 129 WT and TG2^−/− (ii) mice fed a normal chow diet (chow) or fed a normal chow diet for 3 months followed by a high-fat diet for 3 months (fat) or (B) from 3 month old male 129 WT and TG2^−/− mice fed a normal chow diet. (A) Isolated islets, 5 per group (n = 7), were incubated in Krebs-Ringer bicarbonate (KRB) buffer containing 2.8 mM glucose or 16.8 mM glucose or 16.8 mM glucose plus 0.1 mM carbachol, 37°C, 1 h. (B) Groups of 70 islets (n = 3 for WT and n = 2 for TG2^−/−) were perifused in KRB containing 2.8 mM glucose for 10 min before a stimulatory period of 60 min with KRB containing 16.8 mM glucose. The perifusate was switched back to 2.8 mM glucose for 30 min to allow insulin secretion to return to basal levels before exposure to 16.8 mM glucose and 100 µM carbachol for 30 min. The perifusate was switched back to 2.8 mM glucose for 10 min before non-metabolic depolarisation with 24 mM KCl to activate voltage-gated Ca²⁺ channel-triggered insulin secretion. One min fractions of the perifusate were collected for the first 10 min, then 2 min fractions were collected at a flow rate of 0.5 ml/min. Insulin content of supernatant and of islets was determined by radioimmunoassay. Data are presented as means ± SEM. Overall <i>P</i> values calculated using 2-way ANOVA are shown at the top; individual Bonferroni <i>post hoc</i> test results are shown above the columns.**<i>P</i><0.01; ***<i>P</i><0.001.