Fructose Amplifies Counterregulatory Responses to Hypoglycemia in Humans
Fructose Amplifies Counterregulatory Responses to Hypoglycemia in Humans Ilan Gabriely , Meredith Hawkins , Cristian Vilcu , Luciano Rossetti and Harry Shamoon From the Department of Medicine, Division of Endocrinology and Metabolism, Diabetes Research Center, and General Clinical Research Center, A...
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Published in | Diabetes (New York, N.Y.) Vol. 51; no. 4; pp. 893 - 900 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.04.2002
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Subjects | |
Online Access | Get full text |
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Summary: | Fructose Amplifies Counterregulatory Responses to Hypoglycemia in Humans
Ilan Gabriely ,
Meredith Hawkins ,
Cristian Vilcu ,
Luciano Rossetti and
Harry Shamoon
From the Department of Medicine, Division of Endocrinology and Metabolism, Diabetes Research Center, and General Clinical
Research Center, Albert Einstein College of Medicine, Bronx, New York
Abstract
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- 3 H]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.
Footnotes
Address correspondence and reprint requests to Ilan Gabriely, MD, Diabetes Research Center, Albert Einstein College of Medicine,
1300 Morris Park Ave., Bronx, NY 10461. E-mail: gabriely{at}aecom.yu.edu .
Received for publication 3 October 2001 and accepted in revised form 17 December 2001.
CNS, central nervous system; EGP, endogenous glucose production; FK, fructokinase; GCRC, General Clinical Research Center;
GK, glucokinase; GKRP, GK regulatory protein; HNF-1α, hepatocyte nuclear factor-1α; MODY, maturity-onset diabetes of the young;
VMH, ventro-medial hypothalamus.
DIABETES |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0012-1797 1939-327X |
DOI: | 10.2337/diabetes.51.4.893 |