Intermediary Metabolism Of Fat Research Articles

The thrifty genotype in type 2 diabetes: an unfinished symphony moving to its finale?

The basic premise of the thrifty gene hypothesis is that certain populations may have genes that determine increased fat storage, which in times of famine represent a survival advantage, but in a modern environment result in obesity and type 2 diabetes. The concept finds support in a unique animal model (Psammomys obesus) as well as among high type 2 diabetes susceptibility populations, such as North American Indians and South Pacific islanders. However, in some developing communities (e.g., Black South Africans) the thrifty phenotype hypothesis of perinatal malnutrition causing beta-cell dysfunction seems a better explanation, but this remains a contentious issue. Several genes have already been identified as candidates for the thrifty genotype, including those encoding proteins of the insulin-signaling and leptin pathways, as well as intermediary fat metabolism. Particular interest lies in the peroxisome-proliferator activated receptors. An innovative approach might be to focus on the "mirror image" of the thrifty genotype-congenital lipoatrophic diabetes mellitus, whose molecular defect remains enigmatic. We conclude that the genetic basis of the thrifty genotype probably derives from the multiplicative effects of polymorphisms at several sites mentioned above, rather than a single regulatory abnormality.

The effect of an intravenous fat emulsion on liver function.

Fat emulsions have been investigated extensively in an effort to find a safe source of calories for malnourished patients being maintained on parenteral feeding for prolonged periods. However, little attention has been paid to the effect of these emulsions on liver function. In view of the major role of the liver in intermediary fat metabolism and the frequent occurrence of accumulation of fat within the hepatic parenchyma, it seemed of interest to investigate the effects of repeated infusions of fat on the functions and structure of the liver. Methods Daily infusions of 600 ml. of a fat emulsion were given to 20 hospitalized male patients. Ten patients had normal and 10 had abnormal liver function prior to the infusions, as judged by sulfobromophthalein U. S. P. (Bromsulphalein) retention. The patients were selected on the basis of their cooperativeness and their availability for biopsies and follow-up studies. The fat emulsion (Lipomul-I.

Inactivation of Insulin by Intermediary Fat Metabolism Products

IT has been recorded by several workers that insulin, though effective in most diabetics in lowering the blood-sugar level to normal, in a small fraction of cases either does not react at all or very high doses are required for beneficial results. Rosenthal1 observed that one of his patients showed no relief in hyperglycæmia even by daily injections of 100–120 units of insulin. Isolation of inactive insulin has been reported by Bhima Rao et al.2, and Himsworth3 reports on diabetics insensible to insulin. Joslin4 regards adiposity as a precursor of diabetes and this idea has recently been supported by our evidence5 that disturbance in the intermediary metabolism of fat is one of the factors responsible for the onset of hyperglycæmia. It has also been observed that hyperglycæmia caused by repeated injections of pyruvic acid, aceto-acetic ester, and -hydroxy butyric acid, etc., is followed by a rapid fall in blood-sugar level, thus suggesting the possibility of extra stimulation of islet cells. This is to be expected when there is a chance that the internal insulin may be destroyed or inactivated by such substances when administered to the system.

Experimental Hyperglycæmia by Injection of Intermediary Fat Metabolism Products in Rabbits

BEST and his associates1 recently reported hydropic degeneration and degranulation of the β-cells through the injection of anterior pituitary extract similar to those observed in the remnants of Allen's partially depancreatized dogs and ascribe those to overwork. The recent findings of Dunn and his associates2,3 on experimental alloxan diabetes have created great interest in the subject. Though this substance may bring about conditions of glycosuria and hyperglycaemia in animals, the nature of degeneration in the β-cells has been shown to be different from that caused by anterior pituitary injection or through clinical diabetes and the physiological significance has not been known as yet. Adams4 and Joslin5 regard obesity as a precursor of diabetes, and it is reasonable to believe that the intermediary metabolism products formed during improper oxidation of fat might be concerned in causing hyperglycaemia and other associated troubles in an individual. It may be recorded here that repeated injection of these types of chemical substances (for example, β-hydroxy-butyric acid, acetoacetic acid, pyruvic acid, etc.) have been found to cause hyperglycaemia in rabbits.

Notes concerning the cause and treatment ofceliac disease

These objective data suggest that the defect in intestinal absorption of fat and carbohydrate in celiac disease lies within the intestinal mucosa. The absorption of fat in celiac disease, as well as the intestinal motility, absorption of glucose, and the clinical course, are favorably influenced by crude extracts of liver and the B complex of vitamins given parenterally. A tentative plan for the treatment of celiac disease is outlined. We are at present seeking to identify the active factor or factors in these substances and to understand their mode of action in celiac disease and on the intermediary metabolism of fat and carbohydrate in the intestinal mucosa. These objective data suggest that the defect in intestinal absorption of fat and carbohydrate in celiac disease lies within the intestinal mucosa. The absorption of fat in celiac disease, as well as the intestinal motility, absorption of glucose, and the clinical course, are favorably influenced by crude extracts of liver and the B complex of vitamins given parenterally. A tentative plan for the treatment of celiac disease is outlined. We are at present seeking to identify the active factor or factors in these substances and to understand their mode of action in celiac disease and on the intermediary metabolism of fat and carbohydrate in the intestinal mucosa.

Concerning antiketogenesis

It is a well-known fact that the withdrawal of carbohydrates from the diet of normal individuals is followed by the appearance of ketone bodies in the urine. Individuals that have interference with their power to utilize carbohydrates, as diabetics, develop degrees of ketonuria that are proportional to the severity of the disturbances in their carbohydrate metabolism. It is also established definitely that these ketone bodies are formed normally in the intermediary metabolism of fat and of certain amino acids, and that with the oxidation of carbohydrates the ketone bodies suffer oxidation. The carbohydrates therefore are known as antiketogenetic. For a number of years we have been engaged in trying to solve the problem how the carbohydrates exercise their antiketogenetic powers, and to find a chemical explanation for it. We fed to diabetic animals every known chemical compound that may play a röcle in the intermediary metabolism of carbohydrates, and we found that they may be divided into two classes. The first consisting of those substances like glyceric aldehyde, dioxyacetone, pyruvic aldehyde, pyruvic acid and lactic acid, which when given to diabetic animals are completely and directly converted into glucose. They all possess the power of reversible reaction in the body, i.e., they all can be converted from one into the other, and possess but slight antiketogenetic properties because when given to diabetics the main force of the reaction is upwards towards the glucose stage, and as such they become excreted in the urine. Practically none of these are burnt in the body of the diabetic animal. The second consisting of substances like acetaldehyde and perhaps also ethylalcohol. The reaction towards these from glucose and its intermediary products is irreversible, when given to diabetics, they possess marked antiketogenetic powers.