STX does not alter insulin content or blood glucose homeostasis at long-term in male mice.

<p>A, Body weight in male mice before and after the 6 day-treatment with either vehicle or STX; n = 5 mice/condition. B, Fasting glycemia in the following morning after the 6-day treatment with vehicle or STX treated mice (n = 5 mice/condition). C, IPGTT in the same mice as in B; vehicle (•), STX (○); n = 4–5 mice/condition. D, Insulin content in isolated islets from vehicle and STX-treated mice; n = 60–120 islets from 2–3 mice/condition.</p

STX does not change glucose homeostasis in ovariectomized female mice.

<p>A, Intraperitoneal glucose tolerance test (IPGTT) in ovariectomized female mice after one single dose of vehicle (•) or 100 µg/kg STX (○). B, Area under the curve in the IPGTT in A; n = 7–8 mice/condition. C, Body weight in ovariectomized female mice before and after the 6 day-treatment with either vehicle or STX; n = 5–6 mice/condition. D, Fasting glycemia in the following morning after the 6-day treatment with vehicle or STX treated mice (n = 5–6 mice/condition). E, IPGTT in the same mice as in D; vehicle (•), STX (○); n = 5–6 mice/condition. F, Insulin content in isolated islets from vehicle and STX-treated ovariectomized female mice; n = 110–140 islets from 4–6 mice/condition.</p

STX increases glucose-induced plasma insulin levels.

<p>A, Plasma insulin concentration (µg/l) measured at 30 min after a 2 g/kg glucose load in male mice treated with vehicle or 100 µg/kg STX; n≥7 mice/condition. B, Insulin tolerance test (ITT) in male mice after treatment with vehicle or 100 µg/kg STX; n = 11 mice/condition. C, Plasma insulin concentration (µg/l) measured at 30 min after a 2 g/kg glucose load in female mice treated with vehicle or 100 µg/kg STX; n = 5–6 mice/condition. D, Insulin tolerance test (ITT) in female mice after treatment with vehicle or 100 µg/kg STX; n = 7–8 mice/condition. * p<0.05, ** p<0.01.</p

STX enhances calcium entry in islets and isolated β-cells.

<p>A, [Ca²⁺]_i recording of an islet of Langerhans in the presence of 8 mM glucose; 10 nM STX was added to the perfusion when indicated; n = 11 islets from 3 different male mice. B, [Ca²⁺]_i recording of an isolated pancreatic β-cell in the presence of 8 mM glucose; 10 nM STX was added to the perfusion when indicated. C, Area under the curve in [Ca²⁺]_i recordings from isolated β-cells. * p<0.000005; n = 100 cells from 3 different male mice.</p

STX enhances glucose-induced insulin secretion in islets from male mice following a dose-response curve.

<p>A, Measurement of insulin secretion in isolated islets from male mice at different STX concentrations in the presence of 8 mM glucose. The insulin secretion in response to 16 mM glucose was used as an internal control. Insulin secretion experiments were performed for 1 hour, in groups of 5 islets. At least 75 islets were used per condition, from 12 different mice. B, The same as in A, but with islets from female mice. At least 110 islets were used per condition in groups of 5, from 15 different mice. C, Insulin secretion in response to 8 mM glucose in the absence or presence of 10 nM STX, 1 µM or 10 µM ICI 182,780 as indicated. Between 20 and 80 islets were used per condition in groups of 5, from 9 different mice. * p<0.05 <i>vs.</i> 8 mM glucose; # p<10⁻⁴<i>vs.</i> 3 mM glucose; +p<0.05 <i>vs.</i> STX alone.</p

STX improves glucose sensitivity in male mice.

<p>A, Intraperitoneal glucose tolerance test (IPGTT) in male mice after injection of Vehicle (•) or 100 µg/kg STX (○). B, Area under the curve in the IPGTT in males; n = 6–7 mice/condition. C, IPGTT in female mice. D, Area under the curve in the IPGTT in females; n = 7 mice/condition. * p<0.05, ** p<0.01.</p

Long-term treatment with STX does not improve glucose homeostasis in a model of mild diabetes.

<p>A, IPGTT in control mice or treated with nicotinamide and streptozotocin (STZ) to generate glucose intolerance. B, IPGTT in the same mice after 6 days treatment with either vehicle (Control •; STZ-Vehicle ▾) or 100 µg/Kg STX (STZ-STX ○); n = 5–8 mice/condition; * p<0.005; ** p<0.001; # p<0.0005; p = 0.08 STZ-STX vs. STZ-Vehicle at 0 min (fasting glycemia).</p