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The smaller final step from 8mg to 12mg (a 50% increase rather than a 100% doubling) reflects the finding that GI tolerability improves at higher doses once the body has already adapted to substantial receptor activation

In the present study, we examined changes in glucose metabolism in a mouse systemically harboring a loss of function mutation in Insr (a single amino acid substitution from proline to leucine at 1195 amino acid residue (P1195L)), which has been shown to act as a dominant-negative mutant in heterozygosity 6

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