Metabolic Disorders: Hemoglobin A1c (HgbA1c) Levels
HgbA1c is a sub-fraction of hemoglobin formed by the attachment of various sugars to the hemoglobin molecule. In the erythrocytes, the relative amount of hemoglobin A is converted to stable HgbA1c increases with the average concentration of glucose in the blood. The conversion to stable HgbA1c is limited by the erythrocyte's lifespan, so HgbA1c reflects the average blood glucose level during the lifespan of the red blood cells. HgbA1c is a suitable assay to monitor long-term blood glucose control. PTP-1B knockouts display increased glucose tolerance and reduced plasma glucose and insulin levels. Treatment with antisense oligonucleotides against PTP-1B resulted in a significant reduction in HgbA1c levels in ob/ob mice (Zinker et al., 2002). Reduction in HgbA1c levels in PTP-1B knockout mice has been confirmed in our internal phenotypic analysis of this line (data not published). HgbA1c levels have been shown to be significantly higher in KK-Ay and KK diabetic mice as compared to non-diabetic ddY mice (Okazaki et al., 2002). The anticoagulated whole blood specimen is either manually (Hgb%) or automatically (A1c%) hemolyzed. The released hemoglobin is determined on the Cobas Integra 400 (Roche Diagnostics; Indianapolis, IN) in the hemolysate. HgbA1c is then measured using monoclonal antibodies attached to latex particles. The final result is expressed as either percent HgbA1c (automatic hemolysis) or percent Hgb (manual hemolysis) and is a calculated value.
Displayed below is a sample graph of how HgbA1c measures are presented. In comprehensive phenotypic data packages graphs are interactive. Raw or calculated data and statistics can be seen by clicking on points in the graph.
Figure illustrates percentage of HgbA1c in blood of male and female (left), male (center), or female (right) mutant mice. HgbA1c values of wild type littermates (green circle), homozygous (red diamond), and recent historical wild type (purple line) mice are plotted against long-term historical values (± 2 standard deviations) for wild type animals (green shading). Recent wild type values are calculated from data collected within 60 days of current measures and long-term historical values are derived from data collected on more than 10,000 wild type mice.
Okazaki M, Saito Y, Udaka Y, Maruyama M, Murakami H, Ota S, Kikuchi T, Oguchi K. (2002) Diabetic nephropathy in KK and KK-Ay mice, Exp Anim, 51(2):191-6.
Zinker BA, Rondinone CM, Trevillyan JM, Gum RJ, Clampit JE, Waring JF, Xie N, Wilcox D, Jacobson P, Frost L, Kroeger PE, Reilly RM, Koterski S, Opgenorth TJ, Ulrich RG, Crosby S, Butler M, Murray SF, McKay RA, Bhanot S, Monia BP, Jirousek MR (2002) PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice, Proc Natl Acad Sci USA, 2002 99(17):11357-62.