Abstract
For better comprehension of the metabolic syndrome, it is necessary to differentiate the effect of insulin on glucose metabolism on the one hand, and on other metabolic activities on the other hand. Whereas glucose utilization is affected by insulin resistance, the effect of insulin on lipid metabolism, ion and aminoacid transport does not seem to be diminished. Lipid metabolism, however, seems to play a crucial role in the induction of the vicious cycle. Increased energy and fat ingestion may be due to an increased number of galanin secreting cells in the hypothalamus. The excessive fat intake results in an increased rate of release of insulin and increased influx of triglycerides into the blood. From these triglycerides an excess of free fatty acids is released by the action of lipoprotein lipase. The increased plasma free fatty acid level then results in insulin resistance affecting glucose metabolism. Also, these free fatty acids may impair the secretion of insulin. Induction of insulin resistance results in higher glucose levels, which may cause hyperinsulinemia. Hyperinsulinemia maintains the elevation of triglycerides. When diabetes becomes overt and elevated glucose levels prevail, the hyperinsulinism acts on the metabolic pathways which are still sensitive to insulin, namely lipid metabolism, aminoacid transport and ion transport.
Similar content being viewed by others
Abbreviations
- HDL:
-
high density lipoproteins
- NIDDM:
-
non-insulin dependent diabetes mellitus
- oGTT:
-
oral glucose tolerance test
- oMTT:
-
oral metabolic tolerance test
- VLDL:
-
very low density lipoproteins
- WHR:
-
waist-hip ratio
References
Boden, G., Chen, X., Ruiz, J., White, J. V., and Rossetti, L., Mechanisms of fatty acid-induced inhibition of glucose uptake. J. clin. Invest.93 (1994) 2438–2446.
De Fronzo, R. A., Cooke, C. R., Andres, R., Faloona, G. R., and Davis, P. J., The effect of insulin on renal handling of sodium, potassium, calcium and phosphate in man. J. clin. Invest.55 (1975) 845–855.
De Fronzo, R. A., and Ferrannini, E., Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and atherosclerotic cardiovascular disease. Diab. Care14 (1991) 173–194.
Fenselau, S., Diba, A., Keppler, I., Weber, P., Marz, W., Beyer, J., and Schrezenmeir, J., Apolipoprotein phenotypes in NIDDM, high and normal triglyceride responders. Diabetologia37 (Suppl. 1) (1994) A 86.
Ferrannini, E., Barett, E. J., Bevilacquas, and De Fronzo, R. A., Effect of fatty acids on glucose production and utilisation in man. J. clin. Invest.72 (1983) 1737–1747.
Fraze, E., Donner, C. C., and Swislocki, A. L. M., Ambient plasma free fatty acid concentrations in NIDDM: evidence for insulin resistance. J. clin. Endocrin. Metab.61 (1985) 807–811.
Jain, S. K., Nagi, D. K., Slavin, B. M., Lumb, P. J., and Yudkin, J. S., Insulin therapy in type 2 diabetic subjects suppresses plasminogen activator inhibitor (pai-1) and proinsulin like molecules independently of glycaemic control. Diab. Med.10 (1993) 27–32.
Levy, J. C., Clark, P. M., Hales, C. N., and Turner, C., Normal proinsulin responses to glucose in mild type II diabetic subjects with subnormal insulin response. Diabetes42 (1993) 162–169.
Nagi, D. K., Hendra, T. J., Ryle, A. J., Cooper, T. M., Temple, R. C., Clark, P. M. S., Schneider, A. E., Hales, C. N., and Yudkin, J. S., The relationship of concentrations of insulin, intact proinsulin and 32–33 split proinsulin with cardiovascular risk factors in type 2 (non-insulin-dependent) diabetic subjects. Diabetologia33 (1990) 532–537.
Orth, B., Schrezenmeir, J., Fenselau, S., Hauck, Ch., Hammerschmidt, K. H., and Beyer, J., Oral lipid tolerance test (oLT) detects the constellation of the metabolic syndrome before oral glucose tolerance (oGT) is impaired. Diabetologia37 (Suppl. 1) (1994) A 146.
Reaven, G., Chen, X. D., Hollenbeck, C. B., Sheu, W. H., and Ostrega, D., Polensky, K. S., Plasma insulin, C-Peptide and proinsulin concentration in obese and non obese individuals with varying degrees of glucose tolerance. J. clin. Endocrin. Metab.76 (1993) 44–48.
Schrezenmeir, J., Weber, P., Probst, R., Biesalski, H. K., Luley, C., Prellwitz, W., Krause, U., and Beyer, J., Postprandial pattern of triglyceride-rich lipoprotein in normal-weight humans after an oral lipid load: exaggerated triglycerides and altered insulin response in some subjects. Ann. Nutr. Metab.36 (1992) 186–196.
Schrezenmeir, J., Keppler, I., Fenselau, S., Weber, P., Biesalski, H. K., Probst, R., Laue, C., Zuchhold, H. D., Prellwitz, W., and Beyer, J., The phenomenon of a high triglyceride response to an oral lipid load in healthy subjects and its link to the metabolic syndrome. Ann. N.Y. Acad. Sci.683 (1993) 302–314.
Schrezenmeir, J., Keppler, I., Abel, J., Fenselau, S., Weber, P., and Beyer, J., Dissociation of insulin sensitivity towards glucose and fat metabolism at an early stage of the metabolic syndrome. Int. J. Obesity17 (Suppl. 2) (1993) 97.
Schrezenmeir, J., Clark, P., Fenselau, S., Abel, J., Beyer, J., and Hales, C. N., Incomplete proinsulin processing in subjects with postprandial high triglyceride response (premetabolic syndrome). Exp. clin. Endocr.102 (Suppl. 2) (1994) 175.
Schrezenmeir, J., Fenselau, S., Strausberger, B., and Schandl, L., Association of increased adrenal reactivity with abdominal adipose tissue, high postprandial triglyceride response and increased dietary induced thermogenesis. Exp. clin. Endocr.103 (Suppl. 1) (1995) 82.
Schrezenmeir, J., Koffler, Th., Busch, D., Bohl, J., and Strack, T., Increased expression of galanin in nucleus arcuatus hypothalami may play a pathogenetic role in NIDDM. Int. J. Obes.17 (Suppl. 2) (1993) 66.
Singer, P., Godicke, W., Voigt, S., Hajdu, I., and Weiss, M., Postprandial hyperinsulinemia in patients with mild essential hypertension, Hypertension7 (1985) 182–186.
Stout, R. W., Development of vascular lesions in insulin treated animals fed a normal diet. Brit. med. J.3 (1970) 685–687.
Stout, R. W., Bierman, E. L., and Rioss, R., Effect of insulin on the proliferation of cultured primate arterial smooth muscle cell. Circ. Res.36 (1975) 319–327.
Stout, R. W., Diabetes and atherosclerosis, the role of insulin. Diabetologia16 (1979) 141–150.
Stout, R. W., Insulin and atheroma: 20-year perspective. Diab. Care13 (1990) 631–654.
Taggart, H., and Stout, R. W., Control of DNA synthesis in cultured vascular endothelial and smooth muscle cells. Atherosclerosis37 (1980) 549–557.
Temple, R. C., Carrington, C. A., Luzio, S. D., Owens, D. R., Schneider, A. E., Sobey, W. J., and Hales, C. N., Insulin deficiency in NIDDM. Lancet1 (1989) 293–295.
Tshunehara, C. H., Leonetti, D. J., and Fujimoto, W. Y., Diet of second-generation Japanese-American men with and without now insulin dependent diabetes. Am. J. clin. Nutr.52 (1990) 731–738.
Zhou, Y. P., and Grill, V. E., Long term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle. J. clin. Invest.93 (1994) 870–876.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schrezenmeir, J. Hyperinsulinemia, hyperproinsulinemia and insulin resistance in the metabolic syndrome. Experientia 52, 426–432 (1996). https://doi.org/10.1007/BF01919311
Issue Date:
DOI: https://doi.org/10.1007/BF01919311