The action of insulin on the penetration of sugars into the perfused heart*

Fisher, R. B.; Lindsay, D. B.

doi:10.1113/jphysiol.1956.sp005480

Cited by 84 publications

(30 citation statements)

References 18 publications

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“…Sorbitol was estimated by titrating the acid liberated on oxidation by sodium metaperiodate. The procedure was the same in principle as that described by Fisher & Lindsay (1955) but 0-3 M-metaperiodate was used instead of 0 03 M, and the titration was performed with N/20-NaOH. Glucose was removed by yeast fermentation before the estimation.…”

Section: Analytical Proceduresmentioning

confidence: 99%

The absorption of water and of some small solute molecules from the isolated small intestine of the rat

Fisher¹

1955

The Journal of Physiology

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Wells (1931) showed that the rate of absorption of water from the small intestine of the dog was dependent on the distension pressure. This observation has formed the basis of a view that water absorption is determined by hydrostatic and osmotic factors. The ability of the intestine to absorb the animal's own serum or an isotonic salt solution requires on this view that the absorption of water should be secondary to the absorption of the protein and salts.The surviving small intestine preparation of Fisher & Parsons (1949) provides means of obtaining further evidence of the nature of water absorption, since osmotic conditions on the two sides of the mucosa can be varied at will, -and a useful range of distension pressures can be employed. This paper describes the effects of alteration of distension pressure, osmotic pressure and other factors on the absorption of water and of urea, creatine and sorbitol.In the original work of Wells, in which very low distension pressures were used, some part, if not all, of the effect of distension might be expected to arise from the separation of mucosal folds with increasing pressure: mucosal epithelium occluded by folding cannot participate in absorptive activity. In the present work, therefore, the lowest distension pressure used has been one known, from microscopic examination of preparations fixed during distension, to separate all mucosal folds.

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Section: Analytical Proceduresmentioning

confidence: 99%

The absorption of water and of some small solute molecules from the isolated small intestine of the rat

Fisher¹

1955

The Journal of Physiology

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“…While abundant work in the isolated perfused heart has demonstrated that insulin at high concentrations stimulates the uptake and metabolism of glucose (7)(8)(9)(10), evidence that insulin at physiologic concentrations regulates heart glucose uptake in vivo is indirect (11). Furthermore, since in vivo insulin lowers plasma FFA levels by inhibiting lipolysis in adipose tissue (12), assessment of insulin's direct role in regulating heart glucose metabolism requires simultaneous estimation of heart fatty acid exchange.…”

Section: Introductionmentioning

confidence: 99%

Regulation by insulin of myocardial glucose and fatty acid metabolism in the conscious dog.

Barrett¹,

Schwartz²,

Francis³

et al. 1984

J. Clin. Invest.

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As bstract. In vivo small doses of insulin inhibit lipolysis, lower plasma FFA, and stimulate glucose disposal. Lowering of plasma FFA, either in the absence of a change in insulin or during combined hyperglycemia and hyperinsulinemia, promotes glucose uptake by heart muscle in vivo. In the isolated perfused heart, large doses of insulin directly stimulate heart glucose uptake. To assess the effect of physiological elevations of plasma insulin upon myocardial glucose and FFA uptake in vivo independent of changes in plasma substrate concentration, we measured arterial and coronary sinus concentrations ofglucose, lactate, and FFA, and coronary blood flow in conscious dogs during a 30 min basal and a 2 h experimental period employing three protocols: (a) euglycemic hyperinsulinemia (insulin clamp, n = 5), (b) euglycemic hyperinsulinemia with FFA replacement (n = 5), (c) hyperglycemic euinsulinemia (hyperglycemic clamp with somatostatin, n = 5).In group 1, hyperinsulinemia (insulin = 73±13 MU/ ml) stimulated heart glucose uptake (7.3±4.4 vs. 28.2±2.8 Mmol/min, P < 0.002), lowered plasma FFA levels by 80% (P < 0.05), and decreased heart FFA uptake (28.4±4 vs. 1.5±0.9, P < 0.01). When the fall in plasma FFA was prevented by FFA infusion (group 2), hyperinsulinemia (86 ± 10 ,U/ml) provoked a lesser (P < 0.05) stimulation of glucose uptake (A = 8.2±4.2 ,mol/min) (plasma glucose = 186±8 mg/100 ml) during somatostatin infusion resulted in only a small rise in plasma insulin (A = 12±7 ,U/ml), and although plasma FFA tended to decline, heart glucose uptake did not rise significantly (A = 5.5±3.2 Amol/min, P = NS). There was no significant change in coronary blood flow during any of the three study protocols.We conclude that, in the dog, insulin at physiologic concentrations: (a) stimulates heart glucose uptake, both directly and by suppressing the plasma FFA concentration, and (b) does not alter coronary blood flow. Hyperglycemia per se has little effect on heart glucose uptake.

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“…The procedures for the anaesthetization of the rats, excision of the hearts and washing of blood from the hearts and the compositions of the perfusate and of the solutions for cooling and washing the hearts are the result of an evolution of technique from that of Bleehen and Fisher [1954] by Fisher and Lindsay [1956], Bronk and Fisher [1957], Zachariah [1961], and Fisher and Gilbert [1970a]. Hearts were removed under ether anaesthesia and transferred to an ice-cold saline solution (NaCl 142 mm, NaHCO3 0-5 mM).…”

Section: Methodsmentioning

confidence: 99%

The Effects of Endogenous and Added Insulin on the Time‐course of Glucose Uptake by the Isolated Perfused Rat Heart

Fisher

'me>O'Brien

1972

Exp Physiol

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A new method for measurement at short intervals of uptake or production of metabolites by a perfused heart has been applied to the study of the time-course of glucose utilization. In the presence of high concentrations of insulin (100 mU/ml.) glucose utilization was constant from the beginning of perfusion at all concentrations of glucose. In the absence of added insulin, when the perfusate glucose concentration was greater than 1 mm, glucose utilization decreased by more than 20% to reach a constant rate after up to one hour of perfusion. At glucose concentrations below 0 5 ml, glucose utilization without insulin was constant, or nearly so, throughout perfusion. These results suggest that endogenous insulin, which may be relatively ineffective in promoting glucose utilization at low glucose concentrations, influences the properties of the isolated heart longer than is generally supposed.By choice of a suitable infusion rate it is possible to use the new method to study metabolic rates at substrate concentrations which it was not previously feasible to use.The major advantage of perfusing the isolated heart with a simple saline medium lies in the control which this affords over the substrates and hormones presented to the heart. Pre-perfusion for 10 to 15 min is commonly used to allow the endogenous hormones and substrates of a freshly excised heart to equilibrate with the perfusate. Thereafter the heart is presumed to be metabolically stable. However, and Fisher and Gilbert [1970b] showed that 30 min were needed in order that the permeability of the isolated rat heart to D-xylose and L-arabinose in the absence of added insulin should decline to a stable minimum. The effect was attributed to the elution of endogenous insulin. It is necessary to be able to measure glucose utilization at short intervals in order to determine whether it declines similarly in the early stages of perfusion. This paper describes a means of doing this in conditions in which the perfusate glucose concentration is almost constant.A new apparatus for cardiac perfusion has been developed which enables a stable metabolic state to be readily established and recognized. A substrate is continuously infused into a constant volume of recirculating perfusate. The system tends to a steady state in which the composition of the perfusate is constant while the heart remains metabolically stable. The properties of the system allow the time-course of utilization of a substrate to be followed continuously. An initial decline in glucose utilization in the absence of added insulin was observed when the perfusate glucose concentration was in excess of 1 mm, but not otherwise. The decline continued for up to 1 hr, suggesting that an insulin-free heart has rarely been studied. When insulin was added initially at high concentration (100 mU/ml.) the glucose utilization was steady throughout the perfusion. We conclude that the decline in the absence of 176

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The action of insulin on the penetration of sugars into the perfused heart*

Cited by 84 publications

References 18 publications

The absorption of water and of some small solute molecules from the isolated small intestine of the rat

The absorption of water and of some small solute molecules from the isolated small intestine of the rat

Regulation by insulin of myocardial glucose and fatty acid metabolism in the conscious dog.

The Effects of Endogenous and Added Insulin on the Time‐course of Glucose Uptake by the Isolated Perfused Rat Heart

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