Jessie H. Ridout

Diet and the insulin content of pancreas.

IT is well known that fasting, or feeding diets rich in fat and poor in carbohydrate, leads to a change in the metabolism of sugar as judged by (1) the glucosuria following glucose administration, (2) the diabetic type of sugar tolerance curve when glucose is given, and (3) the absence of the normal rise in respiratory quotient after glucose administration. There is evidence that the administration of insulin at least partially restores the normal metabolism of carbohydrate. An excellent review of the relevant literature has recently been published by W. H. Chambers [1938]. We have reported in a preliminary communication [Haist, Ridout & Best, 1939] that a very definite change in the insulin content of pancreas may be produced by alterations in diet. In order to investigate this subject it is necessary to have available (1) an experimental animal which will ingest the diets provided and one from which all the pancreatic tissue can be removed without undue difficulty; (2) an extraction procedure which consistently gives optimal yields of insulin from pancreatic tissue; and (3) a method of testing which gives accurate results when relatively small amounts of insulin are available. The first requirements are satisfied when the Wistar rat is used as the test animal. A suitable method for the extraction of insulin is that outlined by Jephcott [1932] and by Scott & Fisher [1938 a]. Satisfactory assays of the insulin content of the extracts are obtained by the mouse method of testing. The results of these investigations which will now be described demonstrate, among other points, that a very definite decrease in the insulin content of pancreas is brought about by fasting or by the ingestion of diets rich in fat.

A study of the source of liver fat using deuterium as an indicator

ONE of the many problems arising out of the recent researches carried out in the Department of Physiology and in this department is the source of the fat which accumulates in the liver when animals are maintained on a diet poor in lipotropic factors and when certain extracts of the anterior pituitary gland are administered. This problem may be attacked by the use of labelled fatty acids. While there are several methods of preparing these ear-marked molecules, none of these possesses all the advantages which may be secured by the use of deuterium. This communication consists of two parts. In the first a microdensity method for the determination of deuterium oxide, elaborated by one of us (H. M. B.), is described. In the second part the results of the application of this method to certain problems of fat mobilization are presented and discussed.

The lipotropic action of methionine

IN 1937 Tucker & Eckstein demonstrated that methionine exerts a lipotropic effect. This has been confirmed in our laboratory [Best & Ridout, 1938] and by Channon, Manifold & Platt [1938]. The latter workers have shown that methionine, under the conditions of their experiments, exerted very little effect upon the deposition of fat in the liver unless the basal diet was such that large amounts of fat were deposited in the livers of the control animals. We have been interested in the lipotropic effects of dand l-methionine and in the failure of large doses of the racemic mixture to produce greater effects than small doses under certain experimental conditions.

The “lipotropic” effect of dietary protein

THE purpose of this paper is to present further evidence as to the effect of certain dietary proteins on the rate of accumulation of fat in the liver [Best, Huntsman and Ridout, 1935]. This action in the case of casein was first demonstrated by Best and Huntsman [1935], and since then it has been repeatedly observed in these departments and in Prof. H. J. Channons laboratory [Channon and Wilkinson, 1935; Beeston, Channon and Wilkinson, 1935].

Choline and liver fat in phosphorus poisoning1

THE possibility that choline might exert some effect on the deposition of fat in the liver, which is known to be produced by poisoning with any one of a large number of chemical substances, has frequently been considered since the action of the base on liver fat was demonstrated [Best and Huntsman, 1932]. It is known that, under certain conditions at least, the principal action of choline is on the neutral fraction of the liver fat [Best, Channon and Ridout, 1934]. It is this component which is chiefly responsible for the increased amount of fat which appears in the liver when chemical substances with effects similar to those of phosphorus are administered to rats. METHODS.

The effect of choline on the fatty liver of carbon tetrachloride poisoning.

IN a previous communication [Best, MacLean & Ridout, 1935] it was shown that when rats maintained on a diet low in lipotropic factors were poisoned with phosphorus, addition of choline to the diet had no effect on the degree of fatty infiltration or damage to the hepatic cells. On the other hand, the addition of choline increased the rate of removal of excess fat which was present in the livers of the poisoned animals. Since it is well known that diets low in choline result in the accumulation of fat in the liver, it was not possible to differentiate between the liver fat which was present due to the lack of choline and that which was caused by phosphorus poisoning. Maintenance of animals on a diet with added choline, sufficient partially to counterbalance the effect of the low-choline diet, should result in a more marked difference in the amounts of fat present in the livers of the poisoned and control animals. This should make it possible to determine if the addition of choline exerts an effect on the fat which has accumulated as a result of the poisoning. This procedure was therefore adopted in the present investigation. Carbon tetrachloride was used in the experiment to be described, since this material produces very fatty livers and the degree of poisoning is more easily controlled than with phosphorus.

Undernutrition and liver fat

IN the course of earlier investigations on the liver fat of white rats it was observed that the use of certain diets, with or without the addition of choline, usually resulted in a considerable loss of weight during the experimental period. Results, showing that this factor, within the limits encountered in the experiments referred to above, does not affect the interpretation of the findings in the choline experiments, have been published previously [Best & Huntsman, 1935; Best et al. 1935]. Furthermore, a diet low in lipotropic factors has now been devised which usually produces a gain in weight for at least a period of 3 weeks. When choline is also supplied [MacLean et al. 1937] the gain is maintained for longer periods. We became interested, however, in the effect of undernutrition on liver fat and are reporting the results of further studies which extend our previous observations.

The effect of diets low in choline

IN a preliminary communication [1935] we have reported that diets deficient in choline and other lipotropic factors produce an accumulation of fat in the livers of white rats. The diet has, in some cases, contained 40 p.c. of fat, in others 20 p.c., but the effect may be observed even when the amount of ingested fat is well below the quantity usually provided in an adequate diet. The administration of choline always prevents the deposition of liver fat, and under certain conditions it appears to act favourably on the gain in weight of the animals. The results also suggest that choline may improve the general condition of the rats, but for reasons which will be stated later an adequate discussion of this matter must await the results of certain further investigations. In this paper we propose to report the results of several further experiments which confirm and extend the preliminary findings.