|Coss-Bu, Jorge -|
|Sunehag, Agneta -|
|Haymond, Morey -|
Submitted to: Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 23, 2009
Publication Date: August 18, 2009
Citation: Coss-Bu, J.A., Sunehag, A.L., Haymond, M.W. 2009. Contribution of galactose and fructose to glucose homeostasis. Metabolism. 58(8):1050-1058. Interpretive Summary: Glucose, fructose, and galactose represent the three monosaccharides (simple sugars) that compose approximately 50% of our caloric intake. These are ingested as sucrose (fructose + glucose), lactose (galactose + glucose), polymers of glucose (maltose, dextrin, limit dextrin, or starches) or as simple sugars. Glucose stimulates insulin secretion, whereas the other two do not. We previously demonstrated that galactose could be converted to glucose in the human liver. Recent studies reported that there was a unique and previously undescribed pathway by which fructose could be converted directly to glucose. Based on our research, two-thirds of the galactose was converted directly to glucose and one-third is converted indirectly. Our data proves that there is no direct route for the conversion of fructose to glucose and this is fundamental information in our understanding as to how the human body processes these sugars.
Technical Abstract: To determine the contributions of galactose and fructose to glucose formation, 6 subjects (26 +/- 2 years old; body mass index, 22.4 +/-0.2 kg/m2) (mean +/- SE) were studied during fasting conditions. Three subjects received a primed constant intravenous infusion of[6,6-2H2] glucose for 3 hours followed by oral bolus ingestion of galactose labeled to 2% with [U-13C galactose (0.72 g/kg); the other 3 subjects received a primed constant intravenous infusion of[6,6-2H2]glucose followed by either a bolus ingestion of fructose alone (0.72 g/kg)(labeled to 2% with [U-13C]fructose), or co-ingestion of fructose (labeled with [U-13C]fructose) (0.72 g/kg) and unlabeled glucose (0.72 g/kg). Four hours after ingestion, subjects received 1 mg of glucagon intravenously to stimulate glycogenolysis. When galactose was ingested alone, the area under the curve (AUC) of [13C6] glucose and[13C3]glucose was 7.28 +/- 0.39 and 3.52 +/- 0.05 mmol/L per 4 hours, respectively. When [U-13C]fructose was ingested with unlabeled fructose or unlabeled fructose plus glucose, no [13C6 glucose was detected in plasma. The AUC of[13C3]glucose after fructose and fructose plus glucose ingestion was 20.21 +/- 2.41 and 6.25 +/- 0.34 mmol/L per 4 hours, respectively. Comparing the AUC for the 13C3 vs 13C6 enrichments, 67% of oral galactose enters the systemic circulation via a direct route and 33% via an indirect route. In contrast, fructose only enters the systemic circulation via the indirect route. Finally, when ingested alone, fructose and galactose contribute little to glycogen synthesis. After the co-ingestion of fructose and glucose with the resultant insulin response from the glucose, fructose is a significant contributor to glycogen synthesis.