1200 HANDBOOK OF PHYSIOLOGY ^ CIRCULATION II 



atherosclerosis in rabbits (164). In chicks, larger 

 doses of these hormones always depress diet-induced 

 hypercholesterolemia; however, the effect on the 

 vascular lesions is inconstant and inconsistent (152, 

 154). This may be due to the second action of the 

 thyroid in producing vascular damage, providing a 

 favorable site for lipid deposition and atherosclerosis. 

 In contrast to the inconsistent effects of excess 

 thyroid hormones, the deficiency of the hormone 

 (hypothyroidism) always produces increased athero- 

 genesis in animals on a potentially atherogenic diet. 

 This has been shown in chicks (154), rats (178), 

 rabbits (165), and monkeys (146). Dogs develop 

 atherosclerotic lesions only when a high-fat, high- 

 cholesterol diet is combined with hypothvroidism 



(158). 



No information is available at present indicating 

 an effect of thyroid hormones on blood coagulation or 

 fibrinolysis. 



It can be concluded from all available data that 

 thyroid hormone has a significant and important 

 effect on cholesterol metabolism. The direct effect on 

 atherosclerosis is undetermined and questionable. 

 The continuing effort to separate calorigenic from 

 hypocholesterolemic effects in thyroid analogues 

 ultimately may alter the utility of thyroid preparations 

 as antiatherogenic substances. 



Pancreatic Hormones 



Studies in man and in experimental animals 

 indicate that two hormonal systems in the pancreas 

 are actively involved in lipid metabolism and, 

 therefore, in the control of the circulating serum 

 lipids. These can operate independently or, more 

 often, in an interrelated manner. 



Knowledge of the two hormonal systems of the 

 pancreas in man has been derived from the study of 

 pancreatitis and diabetes mellitus. In addition, 

 pancreatic enzyme systems are known to influence 

 absorption from the upper digestive tract. Elastase, 

 presumably a pancreatic enzyme, by influencing the 

 elastic tissue in the media of the blood vessels, can 

 change wall permeability and thus modify calcium 

 and lipid deposition in the intima (82). 



chronic pancreatitis. Chronic pancreatitis in man 

 with hyperlipemia and xanthomatosis, without 

 diabetes, was first described by Wiesel (175) in 1905. 

 Binet & Brocq (15) in 1929 reported a transient 

 hyperlipemia and hypercholesterolemia in dogs with 

 experimental pancreatitis. An antifatty liver sub- 



stance high in bound choline was prepared from the 

 pancreas of dogs by Drae;stedt (34, 35). Adlersberg 

 and co-workers carried out the most recent studies on 

 experimental pancreatitis in dogs and rabbits, and 

 also studied chronic pancreatitis in man (7, 167). 

 He described the serum changes as consisting of a 

 two- to three-fold increase in cholesterol and phos- 

 pholipids with a four- to ten-fold increase of total 

 lipids, the triglycerides, rendering the serum 

 lactescent. The mechanism producing these serum 

 lipid changes has not been clarified. An action by way 

 of the enzyme system affecting lipid absorption has 

 to be considered. Also destruction of the a-cells of 

 the islets of Langerhans and their glucagon content 

 may be involved (26). The elevation of triglycerides 

 is considered the primary change leading secondarily 

 to hypercholesterolemia and hyperlipemia by others 

 (47). The significance of these findings in the patho- 

 genesis of atherosclerosis needs further study. 



diabetes mellitus. The grossly and significantly 

 increased incidence of atherosclerosis in individuals 

 with diabetes mellitus has led to numerous clinical 

 and experimental studies on the influence of the 

 hormones of the islets of Langerhans, particularly 

 insulin, on carbohydrate and lipid metabolism and on 

 atherosclerosis. 



The morphology of the arterial lesions in the 

 diabetic does not differ from that in the nondiabetic. 

 The difference between the two, then, is quantitative. 

 However, in diabetes mellitus a characteristic capil- 

 lary lesion in the retina and the kidney is found, 

 consisting of capillary microaneurysms. Changes in 

 serum lipids and complex carbohydrates are usually 

 found when capillary lesions are present. 



Severely atherosclerotic diabetic patients frequentlv 

 show distinct disturbances of lipid and lipoprotein 

 metabolism, including hyperlipemia, hypercho- 

 lesterolemia, hyper-/j-lipoproteinemia, and a marked 

 elevation of esterified fatty acids (5, 16). They also 

 have increased levels of serum polysaccharides. In 

 diabetic acidosis and ketosis marked hyperlipemia and 

 hvpercholesterolemia are present, in addition to 

 hyperglycemia. Insulin treatment results in bringing 

 all three abnormalities toward normal. However, 

 insulin given to normal individuals has no cho- 

 lesterol-lowering effect (20). 



Experimental studies on the effect of diabetes 

 mellitus and of insulin on lipid metabolism and 

 atherosclerosis have been carried out on numerous 

 animal species, including dogs, rabbits, rats, and 

 chicks. In all animals tested, diabetes produced b\ 



