Inclusion of Low Amounts of Fructose With an Intraduodenal Glucose Load Markedly Reduces Postprandial Hyperglycemia and Hyperinsulinemia in the Conscious Dog

Shiota, Masakazu; Moore, Mary Courtney; Galassetti, Pietro; Monohan, Michael; Neal, Doss W.; Shulman, Gerald I.; Cherrington, Alan D.

doi:10.2337/diabetes.51.2.469

Cited by 65 publications

(74 citation statements)

References 73 publications

(70 reference statements)

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“…Accordingly, precursors of F1P, such as fructose or sorbitol (16), are likely to be important for glucose clearance by liver after a meal. Indeed, supply of fructose together with glucose was shown to increase glycogen synthesis by liver in the rat and dog (32,33). Although fructose can be efficient to relieve hyperglycemia in diabetes, the use of fructose as a substituent for glucose for diabetes patients has raised the controversy (34,35).…”

Section: Discussionmentioning

confidence: 99%

Molecular basis for the role of glucokinase regulatory protein as the allosteric switch for glucokinase

Choi¹,

Seo²,

Kyeong³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Glucokinase (GK) is a monomeric allosteric enzyme and plays a pivotal role in blood glucose homeostasis. GK is regulated by GK regulatory protein (GKRP), and indirectly by allosteric effectors of GKRP. Despite the critical roles of GK and GKRP, the molecular basis for the allosteric regulation mechanism of GK by GKRP remains unclear. We determined the crystal structure of Xenopus GK and GKRP complex in the presence of fructose-6-phosphate at 2.9 Å. GKRP binds to a super-open conformation of GK mainly through hydrophobic interaction, inhibiting the GK activity by locking a small domain of GK. We demonstrate the molecular mechanism for the modulation of GK activity by allosteric effectors of GKRP. Importantly, GKRP releases GK in a sigmoidal manner in response to glucose concentration by restricting a structural rearrangement of the GK small domain via a single ion pair. We find that GKRP acts as an allosteric switch for GK in blood glucose control by the liver.hexokinase | sigmoidicity I conformational restriction | type 2 diabetes

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Section: Discussionmentioning

confidence: 99%

Molecular basis for the role of glucokinase regulatory protein as the allosteric switch for glucokinase

Choi¹,

Seo²,

Kyeong³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Although some amount of fructose converts to glucose by its metabolism (Sun and Empie, 2012), fructose does not increase postprandial plasma glucose levels as high as does glucose (Bantle, 2009;Schaefer et al, 2009). In addition, fructose does not signal insulin release and can lower plasma glucose due to stimulation of hepatic glucose uptake (Moore et al, 2000;Shiota et al, 1998Shiota et al, , 2002. Therefore, fructose used to be considered beneficial as an energy source for diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

High fructose diet feeding accelerates diabetic nephropathy in Spontaneously Diabetic Torii (SDT) rats

et al. 2018

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-Diabetic nephropathy (DN) is one of the complications of diabetes and is now the most common cause of end-stage renal disease. Fructose is a simple carbohydrate that is present in fruits and honey and is used as a sweetener because of its sweet taste. Fructose has been reported to have the potential to progress diabetes and DN in humans even though fructose itself does not increase postprandial plasma glucose levels. In this study, we investigated the effects of high fructose intake on the kidney of the Spontaneously Diabetic Torii (SDT) rats which have renal lesions similar to those in DN patients and compared these with the effects in normal SD rats. This study revealed that a 4-week feeding of the high fructose diet increased urinary excretion of kidney injury makers for tubular injury and accelerated mainly renal tubular and interstitial lesions in the SDT rats but not in normal rats. The progression of the nephropathy in the SDT rats was considered to be related to increased internal uric acid and blood glucose levels due to the high fructose intake. In conclusion, high fructose intake exaggerated the renal lesions in the SDT rats probably due to effects on the tubules and interstitium through metabolic implications for uric acid and glucose.

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“…The inclusion of small amounts of fructose with the intraduodenal glucose load augmented NHGU, increased hepatic glycogen synthesis via the direct pathway, and augmented hepatic glycolysis. As a result, postprandial hyperglycemia and insulin release were reduced (46). It has also been shown that fructose administration stimulates hepatic glycogen synthesis in the presence of hyperinsulinemia in healthy subjects (43).…”

mentioning

confidence: 94%

“…The dogs were housed in a facility that met American Association for the Accrediation of Laboratory Animal Care guidelines, and the protocols were approved by the Vanderbilt University Medical Center Animal Care Committee. At least 16 days before an experiment, a laparotomy was performed under general endotrachial anesthesia (15 mg/kg pentothal sodium presurgery and 0.1% isoflurane as an inhalation anesthetic during surgery), and catheters for blood sampling were placed into a femoral artery, the portal vein, and a hepatic vein as previously described (45,46). Transonic flow probes were placed on the hepatic artery and portal vein.…”

Section: Methodsmentioning

confidence: 99%

“…Plasma free fatty acid (FFA) concentration was determined using the Wako nonesterified fatty acid C test (Wako, Osaka, Japan). For determination of plasma glucose 3 H radioactivity, samples were deproteinized with barium hydroxide and zinc sulfate, and the supernatant was evaporated and reconstituted in 1 ml of water, and 10 ml of liquid scintillation fluid [EcoLite (ϩ); ICN Biomedicals, Irvine, CA] were added (45,46). Liver samples were obtained at the end of experiments by anesthetizing the dog with pentobarbital sodium, exposing the liver by laparotomy, and freeze-clamping liver in situ in less than 2 min.…”

mentioning

confidence: 99%

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Inclusion of low amounts of fructose with an intraportal glucose load increases net hepatic glucose uptake in the presence of relative insulin deficiency in dog

Shiota¹,

Galassetti²,

Igawa³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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-The effect of small amounts of fructose on net hepatic glucose uptake (NHGU) during hyperglycemia was examined in the presence of insulinopenia in conscious 42-h fasted dogs. During the study, somatostatin (0.8 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) was given along with basal insulin (1.8 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) and glucagon (0.5 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 ). After a control period, glucose (36.1 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) was continuously given intraportally for 4 h with (2.2 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) or without fructose. In the fructose group, the sinusoidal blood fructose level (nmol/ml) rose from Ͻ16 to 176 Ϯ 11. The infusion of glucose alone (the control group) elevated arterial blood glucose (mol/ml) from 4.3 Ϯ 0.3 to 11.2 Ϯ 0.6 during the first 2 h after which it remained at 11.6 Ϯ 0.8. In the presence of fructose, glucose infusion elevated arterial blood glucose (mol/ml) from 4.3 Ϯ 0.2 to 7.4 Ϯ 0.6 during the first 1 h after which it decreased to 6.1 Ϯ 0.4 by 180 min. With glucose infusion, net hepatic glucose balance (mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) switched from output (8.9 Ϯ 1.7 and 13.3 Ϯ 2.8) to uptake (12.2 Ϯ 4.4 and 29.4 Ϯ 6.7) in the control and fructose groups, respectively. Average NHGU (mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) and fractional glucose extraction (%) during last 3 h of the test period were higher in the fructose group (30.6 Ϯ 3.3 and 14.5 Ϯ 1.4) than in the control group (15.0 Ϯ 4.4 and 5.9 Ϯ 1.8). Glucose 6-phosphate and glycogen content (mol glucose/g) in the liver and glucose incorporation into hepatic glycogen (mol glucose/g) were higher in the fructose (218 Ϯ 2, 283 Ϯ 25, and 109 Ϯ 26, respectively) than in the control group (80 Ϯ 8, 220 Ϯ 31, and 41 Ϯ 5, respectively). In conclusion, small amounts of fructose can markedly reduce hyperglycemia during intraportal glucose infusion by increasing NHGU even when insulin secretion is compromised. diabetes mellitus; hyperglycemia; hyperinsulinemia INDIVIDUALS WITH TYPE 2 DIABETES MELLITUS exhibit excessive postprandial hyperglycemia with a defect in meal-or glucoseinduced suppression of endogenous glucose production (18,21,28,34). Several studies (21,28,34) have demonstrated that the greater net splanchnic glucose release in diabetic compared with nondiabetic subjects after glucose injection was due to excessive endogenous glucose production rather than lower initial splanchnic extraction of the ingested glucose. However, the insulin and glucose concentrations differed in the diabetic and nondiabetic subjects in all of those studies, precluding direct comparison of the efficiency of splanchnic glucose uptake. DeFronzo et al. (15) (15), found decreased splanchnic glucose uptake in diabetic subjects. It is known, however, that in the presence of euglycemia and hyperinsulinemia, there is minimal splanchnic glucose uptake (14,15,23,42). Thus the size of the signal in the above studies was very small. Hyperglycemia combined with hyperinsulinemia, on the other hand, substantially increases glucose uptake by the liver (14,23,42). Recently, Basu et al. (5) carried out a hyperglycemic and hyperins...

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Inclusion of Low Amounts of Fructose With an Intraduodenal Glucose Load Markedly Reduces Postprandial Hyperglycemia and Hyperinsulinemia in the Conscious Dog

Cited by 65 publications

References 73 publications

Molecular basis for the role of glucokinase regulatory protein as the allosteric switch for glucokinase

Molecular basis for the role of glucokinase regulatory protein as the allosteric switch for glucokinase

High fructose diet feeding accelerates diabetic nephropathy in Spontaneously Diabetic Torii (SDT) rats

Inclusion of low amounts of fructose with an intraportal glucose load increases net hepatic glucose uptake in the presence of relative insulin deficiency in dog

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