Splanchnic and renal exchange of infused fructose in insulin-deficient type 1 diabetic patients and healthy controls.
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Fructose raises blood glucose and lactate levels in normal as well as diabetic man, but the tissue origin (liver and/or kidney) of these responses and the role of insulin in determining the end products of fructose metabolism have not been fully established. Splanchnic and renal substrate exchange was therefore examined during intravenous infusion of fructose or saline in six insulin-deficient type I diabetics who fasted overnight and in five healthy controls. Fructose infusion resulted in similar arterial concentrations and regional uptake of fructose in the two groups. Splanchnic glucose output increased threefold in the diabetics but remained unchanged in controls in response to fructose infusion, and the arterial glucose concentration rose more in diabetics (+5.5 mmol/liter) than in controls (+0.5 mmol/liter). Splanchnic uptake of both lactate and pyruvate increased twofold in response to fructose infusion in the diabetics. In contrast, a consistent splanchnic release of both lactate and pyruvate was seen during fructose infusion in controls. In diabetics fructose-induced hyperglycemia was associated with no net renal glucose exchange, while there was a significant renal glucose production during fructose infusion in the controls. In both groups fructose infusion resulted in renal output of lactate and pyruvate. In the diabetics this release corresponded to the augmented uptake by splanchnic tissues. In two diabetic patients given insulin infusion, all responses to fructose infusion were normalized. Fructose infusion in diabetics did not influence either splanchnic ketone body production or its relationship to splanchnic FFA inflow. We conclude that in insulin-deficient, mildly ketotic type I diabetes, (a) both the liver, by virtue of lactate, pyruvate, and fructose-derived gluconeogenesis, and the kidneys , by virtue of fructose-derived lactate and pyruvate production, contribute to fructose-induced hyperglycemia; (b) outcome of hepatic fructose metabolism; and (c) fructose does not exert an antiketogenic effect. These data suggest that while total fructose metabolism is not altered in diabetics, intermediary hepatic fructose metabolism is dependent on the presence of insulin.
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Skeletal muscle accounts for an important proportion of fructose disposal.
“Finally, several lines of evidence indicate that, even though during fructose infusion the initial step of fructose metabolism is mainly hepatic, skeletal muscle accounts for an important proportion of fructose disposal (29–31).”
From Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans (1993) · cites this paper as [31]
30-40% of fructose disposal could not be accounted for by splanchnic or renal tissue and presumably was largely taking place in skeletal muscle.
“by direct measurements of splanchnic and renal substrate exchange during fructose infusion in humans, showing that 30–40% of fructose disposal could not be accounted for by splanchnic or renal tissue and presumably was largely taking place in skeletal muscle (31).”
From Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans (1993) · cites this paper as [31]
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LIVER FAT IN THE METABOLIC SYNDROME AND TYPE 2 DIABETES
Kotronen, A. (2008) · Työväentutkimus Vuosikirja
- Authors
- Björkman, O., Gunnarsson, R., Hagström, E., Felig, P., & Wahren, J.
- Venue
- Journal of Clinical Investigation
- Published
- 1989-01-01
- Volume
- 83
- Issue
- 1
- Pages
- 52-59
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC303642
- OpenAlex
- W2122391499
- Cited by
- 48
- References
- 25
- Citations by year
- 2024: 1 · 2023: 2 · 2020: 5 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 2
- FWCI
- 0.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- fructose metabolism, type 1 diabetes, insulin deficiency, renal glucose production, lactate, pyruvate, gluconeogenesis, ketogenesis, ketone bodies, free fatty acids
- MeSH terms
- Adult, Amino Acids, Diabetes Mellitus, Type 1, Fatty Acids, Nonesterified, Fructose, Gluconeogenesis, Humans, Ketone Bodies, Kidney, Lactates, Male, Splanchnic Circulation, Lactic Acid
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