TY - JOUR
T1 - Fructose amplifies counterregulatory responses to hypoglycemia in humans
AU - Gabriely, Ilan
AU - Hawkins, Meredith
AU - Vilcu, Cristian
AU - Rossetti, Luciano
AU - Shamoon, Harry
PY - 2002
Y1 - 2002
N2 - Glucokinase (GK) is required for cellular glucose sensing, although there is a paucity of data regarding its role in the counterregulatory response to hypoglycemia in humans. Because fructose has been shown to modulate GK activity, we examined the effects of an acute infusion of fructose on hypoglycemia counterregulation in seven lean nondiabetic subjects. Using stepped hypoglycemia clamp studies (5.0, 4.4, 3.9, and 3.3 mmol/l target plasma glucose steps, 50 min each), subjects were studied on two separate occasions, without (control) or with co-infusion of fructose (1.2 mg · kg-1 · min-1). Fructose induced a resetting of the glycemic thresholds for secretion of epinephrine (3.8 ± 0.1 mmol/l) and glucagon (3.9 ± 0.2 mmol/l) to higher plasma glucose concentrations (4.0 ± 0.1 mmol/l [P = 0.006] and 4.1 ± 0.1 mmol/l [P = 0.03], respectively). In addition, the magnitude of increase in epinephrine and glucagon concentrations was higher after administration of fructose (48 and 39%, respectively, P < 0.05 for both). The amplification of these hormonal responses was specific because plasma norepinephrine, growth hormone, and cortisol were comparable in both sets of studies. Endogenous glucose production, measured with [3-3H]glucose, increased by 47% (P < 0.05) in the fructose infusion studies compared with 14% (P = NS) in the control studies. In addition, glucose uptake was more suppressed with fructose infusion (by 33%, P < 0.05). In concert with these effects of fructose on glucose kinetics, average glucose infusion rate was markedly reduced in the fructose infusion studies during the 3.9-mmol/l glucose step (4.6 ± 0.9 vs. 7.4 ± 1.1 μmol · kg-1 · min-1, respectively, P = 0.03) and during the 3.3-mmol/l glucose step (0.5 ± 0.1 vs. 5.2 ± 1.2 μmol · kg-1 · min-1, respectively, P < 0.001), suggesting more potent glucose counterregulation and improved recovery from hypoglycemia with fructose infusion. We conclude that infusion of a catalytic dose of fructose amplifies the counterregulatory response to hypoglycemia by both increases in hormonal activation and augmentation of glucose counterregulation in humans.
AB - Glucokinase (GK) is required for cellular glucose sensing, although there is a paucity of data regarding its role in the counterregulatory response to hypoglycemia in humans. Because fructose has been shown to modulate GK activity, we examined the effects of an acute infusion of fructose on hypoglycemia counterregulation in seven lean nondiabetic subjects. Using stepped hypoglycemia clamp studies (5.0, 4.4, 3.9, and 3.3 mmol/l target plasma glucose steps, 50 min each), subjects were studied on two separate occasions, without (control) or with co-infusion of fructose (1.2 mg · kg-1 · min-1). Fructose induced a resetting of the glycemic thresholds for secretion of epinephrine (3.8 ± 0.1 mmol/l) and glucagon (3.9 ± 0.2 mmol/l) to higher plasma glucose concentrations (4.0 ± 0.1 mmol/l [P = 0.006] and 4.1 ± 0.1 mmol/l [P = 0.03], respectively). In addition, the magnitude of increase in epinephrine and glucagon concentrations was higher after administration of fructose (48 and 39%, respectively, P < 0.05 for both). The amplification of these hormonal responses was specific because plasma norepinephrine, growth hormone, and cortisol were comparable in both sets of studies. Endogenous glucose production, measured with [3-3H]glucose, increased by 47% (P < 0.05) in the fructose infusion studies compared with 14% (P = NS) in the control studies. In addition, glucose uptake was more suppressed with fructose infusion (by 33%, P < 0.05). In concert with these effects of fructose on glucose kinetics, average glucose infusion rate was markedly reduced in the fructose infusion studies during the 3.9-mmol/l glucose step (4.6 ± 0.9 vs. 7.4 ± 1.1 μmol · kg-1 · min-1, respectively, P = 0.03) and during the 3.3-mmol/l glucose step (0.5 ± 0.1 vs. 5.2 ± 1.2 μmol · kg-1 · min-1, respectively, P < 0.001), suggesting more potent glucose counterregulation and improved recovery from hypoglycemia with fructose infusion. We conclude that infusion of a catalytic dose of fructose amplifies the counterregulatory response to hypoglycemia by both increases in hormonal activation and augmentation of glucose counterregulation in humans.
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U2 - 10.2337/diabetes.51.4.893
DO - 10.2337/diabetes.51.4.893
M3 - Article
C2 - 11916904
AN - SCOPUS:0036228446
SN - 0012-1797
VL - 51
SP - 893
EP - 900
JO - Diabetes
JF - Diabetes
IS - 4
ER -