Additional evidence that transaldolase exchange, isotope discrimination during the triose-isomerase reaction, or both occur in humans: effects of type 2 diabetes

Abstract

Objective: To determine whether deuterium enrichment on carbons 5 and 3 (C5/C3) in plasma glucose is influenced by processes other than gluconeogenesis and, if so, whether these processes are altered by type 2 diabetes.

Research design and methods: In this study, 10 obese diabetic and 10 obese nondiabetic subjects were infused intravenously with [3,5-(2)H(2)] galactose enriched at a C5-to-C3 ratio of 1.0 as well as the enrichment of deuterium on C5 and C3 of plasma glucose, measured with nuclear magnetic resonance using the acetaminophen glucuronide method.

Results: The ratio of deuterium enrichment on C5 and C3 of glucose was <1 (P < 0.001) in all of the diabetic and nondiabetic subjects, resulting in a means +/- SE C5-to-C3 ratio that did not differ between groups (0.81 +/- 0.01 vs. 0.79 +/- 0.01, respectively).

Conclusions: That the C5-to-C3 glucose ratio is <1 indicates that transaldolase exchange, selective retention of deuterium at the level of the triose-isomerase reaction, or both occur in humans. This also indicates that the net effect of these processes on the C5-to-C3 ratio is the same in people with and without type 2 diabetes. The possible effects of transaldolase exchange or selective retention of deuterium (or tritium) at the level of the triose-isomerase reaction on tracee labeling and tracer metabolism should be considered when the deuterated water method is used to measure gluconeogenesis or [3-(3)H] glucose is used to measure glucose turnover in humans.

FIG. 1.

The C5-to-C3 ratio of plasma glucose can decrease if unlabeled glyceraldhyde-3-phosphate exchanges with the bottom three carbons of C5– and C3–labeled fructose-1,6-phosphate via the transaldolase reaction (A), if the deuterium on dihydroxyacetone originating from the third carbon of frucose-1,6-posphate is retained relative to that originating from the fifth carbon of fructose-1,6-phosphate due to kinetic isotope effect (i.e., a slower removal) during the triose isomerase reaction (B), or if a combination of both occurs. Hydrogens and oxygens have been omitted for the sake of clarity. C, carbon; D, deuterium; DHAP, dihydroxyacetone phosphate; fructose-1,6-P, fructose-1,6-phosphate; GAP, glyceraldehyde-3-phosphate; glucose-1-P, glucose-1-phosphate; glucose-6-P, glucose-6-phosphate; UDP, uridine-diphosphoglucose.

FIG. 1.

The C5-to-C3 ratio of plasma glucose can decrease if unlabeled glyceraldhyde-3-phosphate exchanges with the bottom three carbons of C5– and C3–labeled fructose-1,6-phosphate via the transaldolase reaction (A), if the deuterium on dihydroxyacetone originating from the third carbon of frucose-1,6-posphate is retained relative to that originating from the fifth carbon of fructose-1,6-phosphate due to kinetic isotope effect (i.e., a slower removal) during the triose isomerase reaction (B), or if a combination of both occurs. Hydrogens and oxygens have been omitted for the sake of clarity. C, carbon; D, deuterium; DHAP, dihydroxyacetone phosphate; fructose-1,6-P, fructose-1,6-phosphate; GAP, glyceraldehyde-3-phosphate; glucose-1-P, glucose-1-phosphate; glucose-6-P, glucose-6-phosphate; UDP, uridine-diphosphoglucose.

FIG. 2.

Glucose (A), C-peptide (B), insulin (C), and glucagon (D) concentrations observed in the diabetic and nondiabetic subjects.

FIG. 3.

The C5-to-C3 ratio of plasma glucose observed in diabetic and nondiabetic subjects following a 5-h intravenous infusion of [3,5-²H₂] galactose enriched with deuterium at a C5-to-C3 ratio of 1.0.