The Effect of Acute Uraemia on Gluconeogenesis in Isolated Perfused Rat Livers

Fröhlich, Jürgen; Schölmerich, Jürgen; Hoppe-Seyler, G.; Maier, K. P.; Talke, H.; Schollmeyer, P.; Gerok, W.

doi:10.1111/j.1365-2362.1974.tb00419.x

Cited by 51 publications

(37 citation statements)

References 26 publications

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“…In niormials, increased alaniniie delivery as providled by ani alaniniie inifutsion resuilts ini incereased alaninie levels (40). These finidings of' increased glutconeogeniesis lin atzoteinici miani correlate wvell with finin(iigs of increased in vitro hepatic gluiconeogeniesis in the urem-ic rat (12,13 (46) and( hepattic gluiconieogeniesis f'romi thiree carbon prectirsors (47). Whereas the eff'ect of' parathyroid hiormionc o)n adlenylate cyclase activity is less thian-the stiimutlation produtced by epiniephri ne o)r glutcagoni, parathyroid h-ormionie levels are suibstanltially elevated in chironiic renial f'ailuire (:36) andi( may' contributetc to the inicreased1 hiepatic gluiconieogemmesis.…”

Section: Discussionmentioning

confidence: 94%

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Abnormal Carbohydrate Metabolism in Chronic Renal Failure

Rubenfeld

Garber²

1978

J. Clin. Invest.

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A B S T R A C T To delineate the potential role of disordered glucose and glucose-precursor kinetics in the abnormal carbohydrate metabolism of chronic renal failure, alanine and glucose production and utilization and gluconeogenesis from alanine were studied in patients with chronic compensated renal insufficiency and in normal volunteers. With simultaneous primed injection-continuous infusions of radiolabeled alanine and glucose, rates of metabolite turnover and precursor-product interrelationships were calculated from the plateau portion of the appropriate specific activity curves. All subjects were studied in the postabsorption state. In 13 patients with chronic renal failure (creatinine = 10.7±1.2 mg/100 ml; mean+SEM), glucose turnover was found to be 1,035+99.3 ,umol/ min. This rate was increased 56% (P = 0.003) over that observed in control subjects (664±33.5 gmol/min). Alanine turnover was 474±96.0 gmol/min in azotemic patients. This rate was 191% greater (P = 0.007) than the rate determined in control subjects (163±19.4 gmol/min). Gluiconeogenesis from alanine and the percent of glucose production contributed by gluconeogenesis from alanine were increased in patients with chronic renal failure (192% and 169%, respectively) as compared to controls (P < 0.05 for each). Alanine utilization for gluconeogenesis was increased from 40.2 ±3.86 gmol/min in control subjects to 143+39.0 ,umol/min in azotemic patients (P < 0.05). The percent of alanine utilization accounted for by gluconeogenesis was not altered in chronic renal insufficiency. In nondiabetic azotemic subjects, mean fasting glucose and Dr. Garber is an investigator at the Howard Hughes Medical Institute. Received for publication 7 October 1.977 and in revised form 8 Februartj 1978. immunoreactive insulin levels were increased 24.3% (P = 0.005) and 130% (P = 0.046), respectively.These results in patients with chronic renal failure demonstrate (a) increased glucose production and utilization, (b) increased gluconeogenesis from alanine, (c) increased alanine prodtuction and uitilization, and (d) a relative impairment to glucose disposal. We conclude that chronic azotemia is characterized by increased rates of glucose and glucose precursor flux and by a relative impairment to glucose disposal. These findings may suggest an underlying hepatic and peripheral insensitivity to the metabolic action of insulin in patients with chronic renal insufficiency.

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Section: Discussionmentioning

confidence: 94%

“…Elevated rates of alanine formation and release may have been described in skeletal muscle of chronically uremic rats (11). Increased hepatic gluconeogenesis has been observed in the acutely uremic rat (12) and in rat liver slices ineuibated in serum obtained from uremic patients (13).…”

Section: Introductionmentioning

confidence: 99%

Abnormal Carbohydrate Metabolism in Chronic Renal Failure

Rubenfeld

Garber²

1978

J. Clin. Invest.

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“…These results suggest increased sensitivity to the gluconeogenic effects of glucagon in uremia. Increased amino acid incorporation into glucose has been observed in perfused rat livers after nephrectomy (42). It should be noted that while dialysis normalized the glucose response to glucagon (Fig.…”

Section: Discussionmentioning

confidence: 99%

Influence of uremia and hemodialysis on the turnover and metabolic effects of glucagon.

Sherwin¹,

Bastl²,

Finkelstein³

et al. 1976

J. Clin. Invest.

196

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A B S T R A C T To evaluate the mechanism and role of hyperglucagonemia in the carbohydrate intolerance of uremia, 19 patients with chronic renal failure (12 of whom had undergone chronic hemodialysis for at least 11 mo) and 35 healthy control subjects were studied. Plasma glucagon, glucose, and insulin were measured in the basal state, after glucose ingestion (100 g), after intravenous alanine (0.15 g/kg), and during a 3-h continuous infusion of glucagon (3 ng/kg per min) which in normal subjects, raised plasma glucagon levels into the upper physiological range.Basal concentrations of plasma glucagon, the increment in glucagon after infusion of alanine, and postglucose glucagon levels were three-to fourfold greater in uremic patients than in controls. The plasma glucagon increments after the infusion of exogenous glucagon were also two-to threefold greater in the uremics. The metabolic clearance rate (MCR) of glucagon in uremics was reduced by 58% as compared to controls. In contrast, the basal systemic delivery rate (BSDR) of glucagon in uremics was not significantly different from controls.Comparison of dialyzed and undialyzed uremics showed no differences with respect to plasma concentrations, MCR, or BSDR of glucagon. However, during the infusion of glucagon, the increments in plasma glucose in undialyzed uremics were three-to fourfold greater than in dialyzed uremics or controls. When the glucagon infusion rate was increased in controls to 6 ng/kg per min to produce increments in plasma glucagon comparable to uremics, the glycemic response remained approximately twofold greater in the undialyzed uremics. The plasma glucose response to glu- cagon in the uremics showed a direct linear correlation with oral glucose tolerance which was also improved with dialysis. The glucagon infusion resulted in a 24% reduction in plasma alanine in uremics but had no effect on alanine levels in controls. It is concluded that (a) hyperglucagonemia in uremia is primarily a result of decreased catabolism rather than hypersecretion of this hormone; (b) sensitivity to the hyperglycemic effect of physiological increments in glucagon is increased in undialyzed uremic patients; and (c) dialysis normalizes the glycemic response to glucagon, possibly accounting thereby for improved glucose tolerance despite persistent hyperglucagonemia. These findings thus provide evidence of decreased hormonal catabolism contributing to a hyperglucagonemic state, and of altered tissue sensitivity contributing to the pathophysiological action of this hormone.

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“…Alanine and glutamine account for the bulk of amino acids released by muscle (21). Studies performed in vitro using an isolated perfused liver model for hepatic gluconeogenesis have demonstrated that uremia is associated with an increased maximal capacity for hepatic glucose production from amino acids (42,43). Because studies performed in vivo as well as in vitro have demonstrated that the rate of alanine delivery can be rate limiting for gluconeogenesis (7,44), the findings of the present study demonstrating an increased rate of alanine production and release from skeletal muscle in uremia, suggest that an increased rate of hepatic gluconeogenesis from alanine may indeed occur in vivo.…”

Section: Discussionmentioning

confidence: 99%