The Relation of Insulin to Liver Metabolism

Levine, Rachmiel; Fritz, Irving B.

doi:10.2337/diab.5.3.209

Cited by 71 publications

(31 citation statements)

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“…There are, however, certain imposing arguments against this interpretation. First, similar responses were demonstrated by Levine and associates (20,26) in dogs from whom livers had been removed. Second, the observations that metabolism of D-xylose is unimpaired in diabetics deprived of insulin (27), and that the rate of disappearance and urinary excretion of infused D-xylose are normal in diabetics off insulin (28), suggest that the hepatic system for handling this pentose is not insulin dependent.…”

Section: Urinary Excretion Of Pentosessupporting

confidence: 62%

“…At times other investigators have purported to have shown a direct effect of insulin in vitro upon glucose uptake and glycogen synthesis of rat liver slices (21), but this subject is controversial and other studies suggest that insulin itself has no direct action on carbohydrate metabolism by the liver of the rat (26). However, in view of the findings of Beam and collaborators, one must consider the possibility that insulin has caused a rapid uptake of D-xylose and L-arabinose by liver in the subjects of this report.…”

Section: Urinary Excretion Of Pentosesmentioning

confidence: 99%

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The Effect of Insulin on Blood Levels of Infused Pentoses in Man

Segal¹,

Wyngaarden²,

Foley³

1957

J. Clin. Invest.

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In 1931 Wierzuchowski (1) showed an influence of insulin on galactose tolerance of dogs. More recently, Levine, Goldstein, Huddlestun, Klein, and Henry (2, 3) demonstrated that insulin lowers the blood levels of D-galactose, D-xylose, and L-arabinose but not of D-arabinose or D-mannose, following their infusion into the eviscerated nephrectomized dog. The volume of distribution of the responsive sugars was increased from 45 to 70 per cent of body weight as a result of insulin administration. It was suggested that the insulin response represented a facilitation of transport of the sugar across the cell membrane into intracellular fluid. In all the responsive sugars the stereochemical structure of carbon atoms 1 to 3 was like that of D-glucose, and these authors suggested that these structural characteristics determined the insulin responsiveness of a sugar.Confirmatory evidence has appeared that insulin affects transport of D-galactose, D-xylose and L-arabinose across the cell membrane in the rat diaphragm (4-6), eviscerate rat (7), perfused rat heart (8) and intact cat (9). However, slow penetration of a number of sugars into muscle of nephrectomized and eviscerated rats has now also been demonstrated, and this slow penetration is increased by insulin for D-lyxose, D-ribose, D-mannose, D-fructose and D-fucose, as well as for D-xylose, D-galactose and L-arabinose (10, 11). Although these results indicate that the concept of structural specificity in carbon atoms 1 to 3 for insulin responsiveness has proved to be too limited in scope, the lack of an effect of insulin upon intracellular entry of sorbitol, mannitol and raffinose is strong evidence that the action of insulin is not simply an acceleration of a process of physical diffusion (12).

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Section: Urinary Excretion Of Pentosessupporting

confidence: 62%

Section: Urinary Excretion Of Pentosesmentioning

confidence: 99%

The Effect of Insulin on Blood Levels of Infused Pentoses in Man

Segal¹,

Wyngaarden²,

Foley³

1957

J. Clin. Invest.

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“…This finding may be of particular importance in experiments designed to demonstrate an hepatic effect of insulin and in the study of possible betacytotropic agents such as tolbutamide which may stimulate the endogenous secretion of insulin (25). The disparate views concerning the hepatic effect of insulin (11)(12)(13) and also the comparative effects of tolbutamide and insulin on peripheral utilization and glucose intermediaries (26)(27)(28) may have their explanations in the data herein presented.…”

Section: Methodsmentioning

confidence: 67%

The Physiologic Significance of the Secretion of Endogenous Insulin Into the Portal Circulation. I. Comparison of the Effects of Glucagon-Free Insulin Administered via the Portal Vein and via a Peripheral Vein on the Magnitude of Hypoglycemia and Peripheral Glucose Utilization1

Madison¹,

Unger²

1958

J. Clin. Invest.

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“…This suggests that fuel presentation rather than a direct effect of insulin may be a more important factor in minute-to-minute glucose production. This hypothesis was clearly reviewed and enforced by Levine and Fritz 10 years ago (61).…”

Section: Resultsmentioning

confidence: 99%

Hormone-fuel interrelationships during fasting.

Cahill¹,

Herrera²,

Morgan³

et al. 1966

J. Clin. Invest.

993

400

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Over 50 years ago, Benedict (2) published his extensive monograph on the metabolism of fasting in man, in which he demonstrated that carbohydrate stores provide a small but significant component of the body's fuel for only the first few days. Thereafter, protein and fat are the sole sources of fuel, the former contributing 15 % of the calories and the latter the balance.The primary role of fat as fuel was apparent to Benedict and his contemporaries; it is plentiful and expendable. The significance of the protein requirement, however, was less clear; in fact, it was not fully understood until nearly 20 years later when the obligatory dependence of the central nervous system on glucose was firmly established (3). Since glycogen stores in man were known to approximate only 200 g, it was readily apparent that glucose has to be derived from protein in order to maintain cerebral metabolism during a prolonged fast. More recently, our understanding of the fasted state has been further clarified by the demonstration that free fatty acid is both the major transport form of lipid leaving adipose tissue (4, 5) and a substrate that is * Submitted for publication January 26, 1966; accepted August 4, 1966. Supported in part by grants from the U. readily utilized by liver, muscle, and many other tissues.Although the above findings provide a basis for understanding the metabolism of fasting, certain areas such as the physiologic role of hormones and the mechanisms controlling glucose production and utilization remain poorly defined. In addition, estimates of glucose turnover (6)(7)(8)(9)(10)(11)(12) or splanchnic glucose production (13-15) during a short fast all greatly exceed the amount that can be contributed by gluconeogenesis (as reflected by urinary nitrogen loss). This study was, therefore, designed to obtain base-line information concerning the metabolic and hormonal response to fasting in normal subjects and in two subjects with mild diabetes in the hope that such information would provide at least partial insight into some of these problems. In brief, we found in the normal subjects that the well-integrated release of peripheral fuels and the maintenance of blood glucose concentrations were probably related to insulin concentrations, suggesting but not necessarily proving that insulin is the primary signal responsible for fuel control during starvation. The studies also suggested that glu-, cose metabolism, particularly by brain, must be decreased in order for man to survive prolonged periods of caloric deprivation. MethodsSubjects. Six normal male subjects were selected to provide a diverse spectrum of body size and shape (Table I). Five (N1, Ns, N4, N5, and N.) were divinity students, and the sixth (N2) was a sporting-goods salesman. All were in perfect health and had been consuming an average diet estimated to contain over 250 g of carbohydrate and 80 g of protein with variable amounts of fat. Subjects N2 and N4 were intentionally selected because of a family history of diabetes; their mothers had maturity-onset...

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The Relation of Insulin to Liver Metabolism

Cited by 71 publications

References 0 publications

The Effect of Insulin on Blood Levels of Infused Pentoses in Man

The Effect of Insulin on Blood Levels of Infused Pentoses in Man

The Physiologic Significance of the Secretion of Endogenous Insulin Into the Portal Circulation. I. Comparison of the Effects of Glucagon-Free Insulin Administered via the Portal Vein and via a Peripheral Vein on the Magnitude of Hypoglycemia and Peripheral Glucose Utilization1

Hormone-fuel interrelationships during fasting.

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