Renal Net Glucose Release In Vivo and Its Contribution to Blood Glucose in Rats

Kida, Kaichi; Nakajo, Shinjiro; Kamiya, Fumitada; Toyama, Yoshiko; Nishio, Takashi; Nakagawa, Hachiro

doi:10.1172/jci109182

Cited by 105 publications

(49 citation statements)

References 22 publications

(28 reference statements)

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“…In 1978, Kida et al [32] found a renal contribution of 25 % to systemic glucose production in rats by injecting a bolus of [ ]glucose concentration following hepatectomy. In intact animals the isotopic net balance approach was not employed until recently, when a significant renal uptake of glucose was shown in dogs accounting for as much as 30 % of glucose removal from the circulation under postabsorptive conditions [11,12].…”

Section: Methodological Considerationsmentioning

confidence: 99%

“…In alloxan-diabetic rats renal gluconeogenesis was increased twofold compared to normal rats [32]. Several issues regarding the underlying mechanism, however, have remained controversial.…”

Section: Diabetes Mellitusmentioning

confidence: 99%

“…Many studies have shown that insulin inhibits gluconeogenesis in vitro in kidney cortex slices [35] and in vivo in diabetic animals treated with insulin [32]. The observation in humans that during euglycaemic-hyperinsulinaemic clamp experiments systemic glucose appearance, the sum of hepatic plus renal, decreases virtually to zero [36] strongly suggests that insulin suppresses renal glucose production in humans.…”

Section: Hormonal Regulation Of Renal Glucose Productionmentioning

confidence: 99%

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Renal glucose production and utilization: new aspects in humans

et al. 1997

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Summary According to current textbook wisdom the liver is the exclusive site of glucose production in humans in the postabsorptive state. Although many animal and in vitro data have documented that the kidney is capable of gluconeogenesis, production of glucose by the human kidney in the postabsorptive state has generally been regarded as negligible. This traditional view is based on net balance measurements which, other than after a prolonged fast or during metabolic acidosis, showed no significant net renal glucose release. However, recent studies have refuted this view by combining isotopic and balance techniques, which have demonstrated that renal glucose production accounts for 25 % of systemic glucose production. Moreover, these studies indicate that glucose production by the human kidney is stimulated by epinephrine, inhibited by insulin and is excessive in diabetes mellitus. Since renal glucose release is largely, if not exclusively, due to gluconeogenesis, it is likely that the kidney is as important a gluconeogenic organ as the liver. The most important renal gluconeogenic precursors appear to be lactate, glutamine and glycerol. The implications of these recent findings on the understanding of the physiology and pathophysiology of human glucose metabolism are discussed. [Diabetologia (1997) 40: 749-757].

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Section: Methodological Considerationsmentioning

confidence: 99%

“…In alloxan-diabetic rats renal gluconeogenesis was increased twofold compared to normal rats [32]. Several issues regarding the underlying mechanism, however, have remained controversial.…”

Section: Diabetes Mellitusmentioning

confidence: 99%

Section: Hormonal Regulation Of Renal Glucose Productionmentioning

confidence: 99%

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Renal glucose production and utilization: new aspects in humans

et al. 1997

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“…The statistical difference between diabetic and lean rats was measured by the unpaired t test: *P Ͻ 0.05. which is responsible for the stimulation of gluconeogenesis in renal cortical slices prepared from rats that have type 1 diabetes (31-33), can be ruled out. Although insulin has been shown repeatedly to inhibit gluconeogenesis in the human kidney in vivo (7,9,13,14) and in one study in the rat kidney in vivo (34), it is unlikely that it did so by a direct mechanism that altered gene expression because experiments that have been performed in the rat kidney indicate that insulin has no direct effect on the activity or synthesis of phosphoenolpyruvate carboxykinase in the kidney of diabetic rats (32,35). Moreover, our study shows that insulin does not inhibit glucose synthesis from lactate in isolated kidney tubules (Table 3).…”

Section: Factors Responsible For Long-term Stimulation Of Renal Glucomentioning

confidence: 99%

Intrinsic Gluconeogenesis Is Enhanced in Renal Proximal Tubules of Zucker Diabetic Fatty Rats

Eid

Bodin²,

Ferrier³

et al. 2006

Journal of the American Society of Nephrology

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Recent studies indicate that renal gluconeogenesis is substantially stimulated in patients with type 2 diabetes, but the mechanism that is responsible for such stimulation remains unknown. Therefore, this study tested the hypothesis that renal gluconeogenesis is intrinsically elevated in the Zucker diabetic fatty rat, which is considered to be an excellent model of type 2 diabetes. For this, isolated renal proximal tubules from diabetic rats and from their lean nondiabetic littermates were incubated in the presence of physiologic gluconeogenic precursors. Although there was no increase in substrate removal and despite a reduced cellular ATP level, a marked stimulation of gluconeogenesis was observed in diabetic relative to nondiabetic rats, with near-physiologic concentrations of lactate (38%), glutamine (51%) and glycerol (66%). This stimulation was caused by a change in the fate of the substrate carbon skeletons resulting from an increase in the activities and mRNA levels of the key gluconeogenic enzymes that are common to lactate, glutamine, and glycerol metabolism, i.e., mainly of phosphoenolpyruvate carboxykinase and, to a lesser extent, of glucose-6-phosphatase and fructose-1,6-bisphosphatase. Experimental evidence suggests that glucocorticoids and cAMP were two factors that were responsible for the long-term stimulation of renal gluconeogenesis observed in the diabetic rats. These data provide the first demonstration in an animal model that renal gluconeogenesis is upregulated by a long-term mechanism during type 2 diabetes. Together with the increased renal mass (38%) observed, they lend support to the view so far based only on in vivo studies performed in humans that renal gluconeogenesis may be stimulated by and crucially contribute to the hyperglycemia of type 2 diabetes.

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“…This implies that tracer-determined GP cannot simply be taken to be liver derived, and data must be inter- (1) showed a more sensitive response of the kidney to insulin than earlier studies (3,5). In line with this, McGuinness et al (2) found that renal GP in the dog also responded to stress hormone infusion.…”

mentioning

confidence: 95%

Renal contribution to glucose production after a brief fast: fact or fancy?

Cherrington¹,

Wasserman²,

McGinness³

1994

J. Clin. Invest.

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Although it has been known for years that the kidneys possess the enzymatic capability to synthesize glucose from gluconeogenic precursors it has generally been felt that they do not contribute to whole body glucose production (GP) after an overnight fast. A recent paper by Cersosimo et al. ( 1 ) challenges this concept and suggests that the renal contribution to GP may be much more significant than previously thought. We recently reported data (2) that agree with those of Cersosimo et al. (1) ( Table I). In both studies (1, 2) catheterization procedures were used to measure net renal balances of labeled and unlabeled glucose. Renal glucose uptake was calculated by dividing the uptake of [3H ]glucose by the arterial [3H]glucose specific activity (SA). Renal GP was calculated as the difference between renal glucose uptake and net renal glucose balance. While the kidneys were taking up glucose in a net sense, they were producing glucose at rates equal to 24 (1 ) and 13% (2) of tracer-determined whole body GP. A similar finding was made in the rat (3). Net renal glucose balance is similar in the dog and human ( 1, 2, 4), but it remains to be determined whether humans, like dogs, exhibit renal GP after a brief fast.Indirect support for a renal contribution to tracer-determined GP comes from an earlier study in which hepatic glucose balance was assessed (2). for -2.6 ,gmol/kg/min of glucose. Given its magnitude, in all likelihood that source was the kidney. The question arises, however, as to whether renal GP calculated as described quantitatively represents "real" GP. There are two technical concerns which must be considered. First, the approach assumes that within the kidney the site of uptake of [3H]glucose precedes the site ofcold glucose entry. Ifthis is not the case then renal uptake would be underestimated. Since the glucose SA drops only slightly (-5%) across the kidney this assumption is of little consequence. Second, it is unclear whether the reduction in the glucose SA which occurs as blood traverses the kidney is the result of the addition of unlabeled glucose or the loss oflabeled glucose in an exchange process. As discussed below this is a more difficult problem.Renal glucose kinetics are unique in that -20% ofthe load of glucose presented to the kidney is filtered at the glomerulus and quantitatively taken into the proximal tubular cells (PTC). Since this cell contains gluconeogenic enzymes (5), has a source of unlabeled glucose-6-phosphate (gluconeogenic precursor uptake), and has a limited but existent glycolytic capacity (5), it is possible that a labeled glucose molecule could exchange with an unlabeled molecule creating "apparent" glucose production. From the perspective of the tracer method it does not matter whether production is "real" or "apparent,"and it must be concluded that the kidneys are responsible for a portion, (albeit small 13-24%) of tracer-determined GP even after a brief fast. This implies that tracer-determined GP cannot simply be taken to be liver derived, and data must be inte...

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Renal Net Glucose Release In Vivo and Its Contribution to Blood Glucose in Rats

Cited by 105 publications

References 22 publications

Renal glucose production and utilization: new aspects in humans

Renal glucose production and utilization: new aspects in humans

Intrinsic Gluconeogenesis Is Enhanced in Renal Proximal Tubules of Zucker Diabetic Fatty Rats

Renal contribution to glucose production after a brief fast: fact or fancy?

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