Figure 1.

Basal glycemia, glucose disposal, plasma insulin and insulin responses in vitro and in vivo in NKCC1^HE mice. (A) Blood glucose levels in fasted NKCC1^WT (black dots, n=26) and NKCC1^HE mice (grey dots, n=58). Values are stated for each genotype and expressed as the means±s.e.m. (*P=0.003). (B) Insulin-induced hypoglycemia in fasted NKCC1^WT (black dots, n=5) and NKCC1^HE mice (grey dots, n=6). Results are plotted as natural logarithms of initial blood glucose, i.e., before insulin injection vs time in minutes. The differences between the slopes of each curve (grey lines), calculated by linear regression analysis, were not statistically different (P=0.816). The 95% confidence limits are indicated as overlapped shaded areas. (C) Basal and glucose-stimulated plasma insulin in fasted NKCC1^WT (black dots, n=3–7) and NKCC1^HE mice (grey dots, n=7–12). Plasma insulin levels either basal or 5 min post-glucose stimuli were not different (NS) in NKCC1^WT (basal: 107.1±5.2 pmol/l, 5 min: 137.7±30.9 pmol/l, P=0.443) but were in NKCC1^HE mice (basal: 25.8±2.4 pmol/l, 5 min: 109.8±21.9 pmol/l, *P=0.010). (D) Intra-peritoneal glucose tolerance tests in NKCC1^WT (black dots, n=7) and NKCC1^HE mice (grey dots, n=10). Basal blood glucose in NKCC1^WT and NKCC1^HE mice is 5.6±0.3 and 4.0±0.3 mM respectively (*P=0.001). Glycemia 15 and 30 min post-glucose stimulus was significantly lower in NKCC1^HE mice relative to NKCC1^WT (*P<0.05). Inset: areas under each GTT curve (NKCC1^WT=9.5±0.6 mM/min, NKCC1^HE=7.9±0.4, *P=0.027). (E) Insulin secretion from equivalent numbers of NKCC1^WT and NKCC1^HE islets (black and grey dots, respectively) challenged with the indicated glucose concentrations. Results are expressed as mean insulin (pmol/l)±s.e.m. present in the culture media (n=5).