Role of Insulin

In support of a causative or accentuating role of abnormal insulin action in EHL are findings of Schlierf and Kinsell (1965) who have shown that intravenous infusion of small amounts of insulin will result in decreased levels of plasma glycerides as compared to the same subject during control infusion with saline solution. Coadministration of protamine, an inhibitor of heparin-induced lipoprotein lipase (Bragdon and Havel 1954) with the insulin inhibits this effect. 

In spite of differences in pathogenesis of the various forms of EHL it is possible to consider their clinical manifestations together since the majority of signs and symptoms seem to vary only in a quantitative manner between syndromes. This, as well as the frequency of asymptomatic cases of EHL, indicates that at least the manifestations of lipemia retinalis, xanthomatosis and probably hepatospleno-megaly and abdominal crises are the results of the lipid elevation rather than primary expressions of the underlying pathogenetic mechanisms. Other evidence for the non-specificity of eruptive xanthomas and lipemia retinalis is their occurrence in secondary hyperlipemias (e.g. diabetic ketoacidosis). 

An excellent review of the subject is that of Crocker (1951). Xanthomatosis is the most common and in many instances the first readily recognizable sign of severe EHL. Thannhauser (1957) has emphasized the early and quite consistent appearance of xanthomas in children with hyperlipemia, whereas in adults they occur in only about 50% of cases. The same figure was given by Barrie (1957) and a similar incidence one year later by Gadrat (xanthomas in 25 out of 49 patients with EHL). A correlation between the prevailing lipoprotein pattern and the different forms of xanthomas has been attempted by Gofman et al. (1954) 

Data about lipid composition of skin xanthomas have been summarized by Schettler (1955, Handbuch, pg. 696) a recent study on xanthoma tuberosum was published by Fletcher and Gloster (1964). In spite of a significant elevation of plasma triglycerides in some of their cases, cholesterol was the prevailing lipid of the lesions. 

Tuberous xanthomas (Fig. 6 a an,d b) have been described in EHL with a predilection for elbows, kne es, hands anck feet. They may occasionally assume bizzare proportions. In other instances differentiation from eruptive xanthomas may be difficult, and has frequently been neglected.Thus Adlersberg (1955) only used the term tuberous xanthomas which he found in 14% of his patients with EHL and 

---

The first hormonal signal found to comply with the characteristics of both a satiety and an adiposity signal was insulin [1]. Insulin levels reflect substrate (carbohydrate) intake and stores, as they rise with blood glucose levels and fall with starvation. In addition, they may reflect the size of adipose stores, because a fatter person secretes more insulin than a lean individual in response to a given increase of blood glucose. This increased insulin secretion in obesity can be explained by the reduced insulin sensitivity of liver, muscle, and adipose tissue. Insulin is known to enter the brain, and direct administration of insulin to the brain reduces food intake. The adipostatic role of insulin is supported by the observation that mutant mice lacking the neuronal insulin receptor (NDRKO mice) develop obesity. 

Clemmons, D. R., W. H. Busby, T. Arai et al. 1995. Role of insulin-like growth factor binding proteins in the control of IGF actions. Prog Growth Factor Res 6(2-4) 357-366. 

Dercole, A. et al. (1996). The role of insulin-like growth factors in the central nervous system. Mol. Neurobiol. 13(3), 227-255. 

Zammit, V.A. (1996) Role of insulin in hepatic fatty acid partitioning emerging concepts. Biochem. J. 314, 1-14. 

Possible roles of insulin-like growth factor in regulation of... 

Everett J. The role of insulin pumps in the management of diabetes. Nurs Times. 2004 100 48-19. 

Oiknine R, Bernbaum M, Mooradian AD. A critical appraisal of the role of insulin analogues in the management of diabetes mellitus. Drugs. 2005 65 325-340. 

Goldstein, B.J., K. Mahadev, X. Wu, L. Zhu, and H. Motoshima. 2005. Role of insulin-induced reactive oxygen species in the insulin signaling pathway. Antiox. Redox Signal. 7 1021-1031. 

Dees WL, Hiney JK, Srivastava V (1998) Alcohol s effects on female puberty The role of insulin-like growth factor 1. Alcohol Health Res World, 22(3) 165-169. 

Mabrouk, G.M., Helmy, I.M., Thampy, K.G., Wakil, S.J. 1990. Acute hormonal control of acetyl-CoA carboxylase. The roles of insulin, glucagon, and epinephrine. J. Biol. Chem. 265, 6330-6338. 

B16. Broughton, D. L., and Taylor, R., Deterioration of glucose tolerance with age The role of insulin resistance. Age Ageing 20,221-225 (1991). 

W3. Wang, Y. Z., and Wong, Y. C., Sex hormone-induced prostatic carcinogenesis in die noble rat die role of insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in the development of prostate cancer. Prostate 35, 165—177 (1998). 

Messier C, Teutenberg K (2005) The role of insulin, insulin growth factor, and insulin-degrading enzyme in brain aging and Alzheimer s disease. Neural Plast 12 311-328 Mohmmad Abdul H, Butterfield DA (2005) Protection against amyloid beta-peptide (1-42)-induced loss of phospholipid asymmetry in synaptosomal membranes by tricyclodecan-... 

The vital role of insulin is best appreciated when we look at the consequences of a lack of insulin and/or a lack of insulin response, leading to excess blood glucose. Hyperglycaemia is responsible for many manifestations of the disease, because it leads to non-enzymic glycation of proteins, as shown by Anthony Cerami (of course, there are other important manifestations of the disease, such as the dysfunction of fatty acid metabolism and the formation of ketone bodies, which have not been considered here see P. J. Randle et... 

The most dramatic effect of insulin is the hormone-dependent uptake of glucose by muscle, as demonstrated by Levine and Goldstein. 8 This directed attention to the role of insulin on glucose uptake in muscle and adipose tissue, and eventually led to the elucidation of an insulin-responsive glucose-uptake mechanism in these tissues. Furthermore,... 

Daughaday WH. The possible autocrine/paracrine and endocrine roles of insulin-ltke growth factors of human tumors. Endocrinology 1990 127 1-4. 

Reaven GM. Banting lecture 1988. Role of insulin resistance in hmnan disease. Diabetes 1988 37 1595-607. 

Seshadri V, Fox PL, MuMiopadhyay CK. Dual role of insulin in transcriptional regulation of the acute phase reactant ceruloplasmin. J Biol Chem 2002 277 27903-11. 

H.F. Zhang, Q. Fan, X.X. Qian, B.L. Lopez, T.A. Christopher, X.L. Ma and F. Gao, Role of insulin in the antiapoptotic effect of glucose-insulin-potassium in rabbits with acute myocardial ischemia and reperfusion. Apoptosis 9, 777-783 (2004). 

---