Evidence for Interindividual Heterogeneity in the Glucose Gradient across the Human Red Blood Cell Membrane and its Relationship to Hemoglobin Glycation
Authors
Khera, Paramjit K.Joiner, Clinton H.
Carruthers, Anthony
Lindsell, Christopher J.
Smith, Eric P.
Franco, Robert S.
Holmes, Yancey R.
Cohen, Robert M.
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2008-09-01Keywords
AdultCarbon Radioisotopes
Diabetes Mellitus
Erythrocyte Membrane
Erythrocytes
Female
Fructosamine
Glucose
Glycosylation
Guanosine
Hemoglobin A, Glycosylated
Homeostasis
Humans
Male
Middle Aged
Models, Biological
Risk Factors
Urea
Water
Biochemical Phenomena, Metabolism, and Nutrition
Biochemistry, Biophysics, and Structural Biology
Metadata
Show full item recordAbstract
OBJECTIVE: To determine whether interindividual heterogeneity in the erythrocyte (red blood cell [RBC]) transmembrane glucose gradient might explain discordances between A1C and glycemic control based on measured fructosamine. RESEARCH DESIGN AND METHODS: We modeled the relationship between plasma glucose and RBC glucose as the concentration distribution (C(i)-to-C(o) ratio) of a nonmetabolizable glucose analog (14)C-3-O-methyl glucose ((14)C-3OMG) inside (C(i)) and outside (C(o)) RBCs in vitro. We examined the relationship between that distribution and the degree of glycation of hemoglobin in comparison with glycation of serum proteins (fructosamine), the glycation gap. A1C, fructosamine, and in vitro determination of the (14)C-3OMG distribution in glucose-depleted RBCs were measured in 26 fasted subjects. RESULTS: The C(i)-to-C(o) ratio 0.89 +/- 0.07 for 3-O-methyl-d-glucopyranose (3OMG) ranged widely (0.72-1.04, n = 26). In contrast, urea C(i)-to-C(o) (1.015 +/- 0.022 [range 0.98-1.07], P < 0.0001) did not. Concerning mechanism, in a representative subset of subjects, the C(i)-to-C(o) ratio was retained in RBC ghosts, was not dependent on ATP or external cations, and was reestablished after reversal of the glucose gradient. The 3OMG C(i)-to-C(o) ratio was not correlated with serum fructosamine, suggesting that it was independent of mean plasma glucose. However, C(i)-to-C(o) did correlate with A1C (R(2) = 0.19) and with the glycation gap (R(2) = 0.20), consistent with a model in which differences in internal glucose concentration at a given mean plasma glucose contribute to differences in A1C for given level of glycemic control. CONCLUSIONS: The data demonstrate interindividual heterogeneity in glucose gradients across RBC membranes that may affect hemoglobin glycation and have implications for diabetes complications risk and risk assessment.Source
Diabetes. 2008 Sep;57(9):2445-52. Epub 2008 Jun 30. Link to article on publisher's siteDOI
10.2337/db07-1820Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26123PubMed ID
18591386Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.2337/db07-1820