Extended Data Fig. 3: Impaired counter-regulation in NOD mice with T1D and correction by CYN154806.
a-b, Changes in plasma glucose (a) and glucagon (b) in the absence (o; n = 8) and presence (•; n = 6) of CYN154806 in adult ND NOD mice. Insulin (0.75U/kg body weight) was injected at t = 0 (black arrow in a) and CYN154806 (0.5 mg/kg body weight) or vehicle was injected at t = −15 min (red arrow in a). c-d, As in (a-b) but using age-matched T1D NOD mice (n = 8 without and 5 with CYN154806). *p < 0.05 vs without CYN, two-sided Student’s t-test. e, Changes in plasma glucose (black) and glucagon (red) in T1D NOD mice (n = 3). Insulin (0.75U/kg body weight) was injected at t = 0 and 30 min (arrows). f, Plasma glucagon during hypoglycaemia induced by two consecutive insulin injections (0.75U/kg body weight) in T1D NOD mice (to lower plasma glucose to levels similar to those observed in ND mice). Data are expressed as the area under the curve (AUC) above basal (t = 30 min) during the 45 min following the second insulin injection (n = 3). For comparison, the responses in ND NOD mice are shown (mean value [dashed circle] ± S.E.M. [dashed lines], data taken from Fig. 1j); *p = 0.029 vs ND NOD mice, two-sided Student’s t-test. g-h, Relationship of plasma glucagon and glucose in ND (g) and T1D (h) NOD mice during insulin-induced hypoglycaemia in the absence (black) and presence (red) of CYN154806. Dashed lines mark the linear regression fittings of the data. Values of slopes (pM/mM) are given as well as the p values of the respective relationships obtained in the absence (vehicle) or presence of CYN154806. Statistical significance was evaluated using t-test. i, Glycogen content in livers from adult ND (n = 24) and T1D NOD (n = 9) mice. *p = 0.038 vs ND, two-sided Student’s t-test. In dot plots, rectangles and error bars behind data points represent mean values ± S.E.M.
