Decreased glucose tolerance with age following activation of mutGCK.
IPGTT: activation of beta-mutGCK has no effect on glucose tolerance at the age
of 1.5 months (a) (n=8 beta-mutGCK and 9 control
mice), but resulted in impaired glucose tolerance by the age of 8 months
(b) (n=10 beta-mutGCK and 9 control mice). Ex
vivo dynamic measurements of insulin secretion, normalised to unmethylated DNA
of the insulin 2 gene (perifusion): insulin secretion at age 1.5 months
(c) and at 8 months of age (d)
(n=6 mice/group). (e) Glucose response to i.p.
insulin in mice pre-treated with diazoxide showing similar glucose clearance in
WT and beta-mutGCK mice (n=8 beta-mutGCK and 6 control mice).
(f) Left, beta cell mass [(pancreas weight × %beta
cells)/body weight] in WT and mutant mice at the age of 1.5 months (young)
(n=7 mice in each group) and at 8 months of age (old)
(n=10 mice in each group). 2.8G, 2.8mmol/l glucose; 16.8G,
16.8 mmol/l glucose; BCM, beta cell mass; unmeth, unmethylated. Bars represent
standard error (*p<0.05,
**p<0.001).