Abstract
Previous studies have shown cellular insulin resistance in conventionally treated insulin-dependent diabetics. To determine whether insulin resistance is also present in insulin-dependent diabetics before the commencement of insulin therapy, we studied nine newly diagnosed untreated insulin-dependent diabetics and nine control subjects. Insulin binding to adipocytes, monocytes, and erythrocytes was normal in the diabetic individuals. Basal (noninsulin stimulated) glucose transport rate was normal, whereas the maximal insulin responsiveness of glucose transport was severely impaired (P less than 0.02). Insulin sensitivity as judged by left or rightward shifts in the insulin dose-response curves was unchanged. Moreover, the basal lipogenesis rate measured at a glucose concentration of 0.5 mmol/liter was decreased in the diabetics (P less than 0.05), and the maximal insulin responsiveness of lipogenesis was also reduced (P less than 0.05). We conclude that fat cells from untreated insulin-deficient diabetics are insulin resistant. The major defects are (1) reduced maximal insulin responsiveness of glucose transport and conversion to lipids that are postbinding abnormalities, and (2) reduced basal glucose conversion to lipids.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barrett E. J., DeFronzo R. A., Bevilacqua S., Ferrannini E. Insulin resistance in diabetic ketoacidosis. Diabetes. 1982 Oct;31(10):923–928. doi: 10.2337/diab.31.10.923. [DOI] [PubMed] [Google Scholar]
- Beck-Nielsen H., Pedersen O., Kragballe K., Sorensen N. S. The monocyte as a model for the study of insulin receptors in man. Diabetologia. 1977 Dec;13(6):563–569. doi: 10.1007/BF01236308. [DOI] [PubMed] [Google Scholar]
- Beck-Nielsen H., Richelsen B., Hasling C., Nielsen O. H., Heding L., Sørensen N. S. Improved in vivo insulin effect during continuous subcutaneous insulin infusion in patients with IDDM. Diabetes. 1984 Sep;33(9):832–837. doi: 10.2337/diab.33.9.832. [DOI] [PubMed] [Google Scholar]
- Bratusch-Marrain P. R., Smith D., DeFronzo R. A. The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab. 1982 Nov;55(5):973–982. doi: 10.1210/jcem-55-5-973. [DOI] [PubMed] [Google Scholar]
- Christensen N. J. Plasma norepinephrine and epinephrine in untreated diabetics, during fasting and after insulin administration. Diabetes. 1974 Jan;23(1):1–8. doi: 10.2337/diab.23.1.1. [DOI] [PubMed] [Google Scholar]
- Cigolini M., Smith U. Human adipose tissue in culture. VIII. Studies on the insulin-antagonistic effect of glucocorticoids. Metabolism. 1979 May;28(5):502–510. doi: 10.1016/0026-0495(79)90189-6. [DOI] [PubMed] [Google Scholar]
- DeFronzo R. A., Hendler R., Simonson D. Insulin resistance is a prominent feature of insulin-dependent diabetes. Diabetes. 1982 Sep;31(9):795–801. doi: 10.2337/diab.31.9.795. [DOI] [PubMed] [Google Scholar]
- DeFronzo R. A., Jacot E., Jequier E., Maeder E., Wahren J., Felber J. P. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes. 1981 Dec;30(12):1000–1007. doi: 10.2337/diab.30.12.1000. [DOI] [PubMed] [Google Scholar]
- DeFronzo R. A., Simonson D., Ferrannini E. Hepatic and peripheral insulin resistance: a common feature of type 2 (non-insulin-dependent) and type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1982 Oct;23(4):313–319. doi: 10.1007/BF00253736. [DOI] [PubMed] [Google Scholar]
- Deibert D. C., DeFronzo R. A. Epinephrine-induced insulin resistance in man. J Clin Invest. 1980 Mar;65(3):717–721. doi: 10.1172/JCI109718. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Del Prato S., Nosadini R., Tiengo A., Tessari P., Avogaro A., Trevisan R., Valerio A., Muggeo M., Cobelli C., Toffolo G. Insulin-mediated glucose disposal in type I diabetes: evidence for insulin resistance. J Clin Endocrinol Metab. 1983 Nov;57(5):904–910. doi: 10.1210/jcem-57-5-904. [DOI] [PubMed] [Google Scholar]
- Heding L. G. Radioimmunological determination of human C-peptide in serum. Diabetologia. 1975 Dec;11(6):541–548. doi: 10.1007/BF01222104. [DOI] [PubMed] [Google Scholar]
- Hidaka H., Howard B. V., Ishibashi F., Kosmakos F. C., Craig J. W., Bennett P. H., Larner J. Effect of pH and 3-hydroxybutyrate on insulin binding and action in cultured human fibroblasts. Diabetes. 1981 May;30(5):402–406. doi: 10.2337/diab.30.5.402. [DOI] [PubMed] [Google Scholar]
- Hjøllund E., Pedersen O., Richelsen B., Beck-Nielsen H., Sørensen N. S. Increased insulin binding to adipocytes and monocytes and increased insulin sensitivity of glucose transport and metabolism in adipocytes from non-insulin-dependent diabetics after a low-fat/high-starch/high-fiber diet. Metabolism. 1983 Nov;32(11):1067–1075. doi: 10.1016/0026-0495(83)90079-3. [DOI] [PubMed] [Google Scholar]
- ITAYA K., UI M. COLORIMETRIC DETERMINATION OF FREE FATTY ACIDS IN BIOLOGICAL FLUIDS. J Lipid Res. 1965 Jan;6:16–20. [PubMed] [Google Scholar]
- Jørgensen K. H., Larsen U. D. Homogeneous mono-(125)i-insulins. Preparation and characterization of mono-(125)i-(tyr a14)-and mono-(125)i-(tyr a19)-insulin. Diabetologia. 1980;19(6):546–554. doi: 10.1007/BF00253183. [DOI] [PubMed] [Google Scholar]
- Karnieli E., Hissin P. J., Simpson I. A., Salans L. B., Cushman S. W. A possible mechanism of insulin resistance in the rat adipose cell in streptozotocin-induced diabetes mellitus. Depletion of intracellular glucose transport systems. J Clin Invest. 1981 Sep;68(3):811–814. doi: 10.1172/JCI110318. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kashiwagi A., Verso M. A., Andrews J., Vasquez B., Reaven G., Foley J. E. In vitro insulin resistance of human adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus. J Clin Invest. 1983 Oct;72(4):1246–1254. doi: 10.1172/JCI111080. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kobayashi M., Olefsky J. M. Effects of streptozotocin-induced diabetes on insulin binding, glucose transport, and intracellular glucose metabolism in isolated rat adipocytes. Diabetes. 1979 Feb;28(2):87–95. doi: 10.2337/diab.28.2.87. [DOI] [PubMed] [Google Scholar]
- Lager I., Lönnroth P., von Schenck H., Smith U. Reversal of insulin resistance in type I diabetes after treatment with continuous subcutaneous insulin infusion. Br Med J (Clin Res Ed) 1983 Dec 3;287(6406):1661–1664. doi: 10.1136/bmj.287.6406.1661. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lönnroth P., Blohmé G., Lager I., Tisell L. E., Smith U. Insulin resistance in fat cells from insulin-treated type I diabetic individuals. Diabetes Care. 1983 Nov-Dec;6(6):586–590. doi: 10.2337/diacare.6.6.586. [DOI] [PubMed] [Google Scholar]
- Mandarino L., Baker B., Rizza R., Genest J., Gerich J. Infusion of insulin impairs human adipocyte glucose metabolism in vitro without decreasing adipocyte insulin receptor binding. Diabetologia. 1984 Sep;27(3):358–363. doi: 10.1007/BF00304850. [DOI] [PubMed] [Google Scholar]
- Nankervis A., Proietto J., Aitken P., Alford F. Impaired insulin action in newly diagnosed type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1984 Nov;27(5):497–503. doi: 10.1007/BF00290383. [DOI] [PubMed] [Google Scholar]
- Oka Y., Czech M. P. Photoaffinity labeling of insulin-sensitive hexose transporters in intact rat adipocytes. Direct evidence that latent transporters become exposed to the extracellular space in response to insulin. J Biol Chem. 1984 Jul 10;259(13):8125–8133. [PubMed] [Google Scholar]
- Olefsky J. M. Decreased insulin binding to adipocytes and circulating monocytes from obese subjects. J Clin Invest. 1976 May;57(5):1165–1172. doi: 10.1172/JCI108384. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orskov H., Thomsen H. G., Yde H. Wick chromatography for rapid and reliable immunoassay of insulin, glucagon and growth hormone. Nature. 1968 Jul 13;219(5150):193–195. doi: 10.1038/219193b0. [DOI] [PubMed] [Google Scholar]
- Pedersen O., Beck-Nielsen H., Heding L. Increased insulin receptors after exercise in patients with insulin-dependent diabetes mellitus. N Engl J Med. 1980 Apr 17;302(16):886–892. doi: 10.1056/NEJM198004173021603. [DOI] [PubMed] [Google Scholar]
- Pedersen O., Beck-Nielsen H., Sørensen N. S., Svejgaard A. Heterogeneity of insulin receptors in patients with untreated insulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1982 Jul;55(1):30–39. doi: 10.1210/jcem-55-1-30. [DOI] [PubMed] [Google Scholar]
- Pedersen O., Hjøllund E., Beck-Nielsen H., Lindskov H. O., Sonne O., Gliemann J. Insulin receptor binding and receptor-mediated insulin degradation in human adipocytes. Diabetologia. 1981 Jun;20(6):636–641. [PubMed] [Google Scholar]
- Pedersen O., Hjøllund E. Insulin receptor binding to fat and blood cells and insulin action in fat cells from insulin-dependent diabetics. Diabetes. 1982 Aug;31(8 Pt 1):706–715. doi: 10.2337/diab.31.8.706. [DOI] [PubMed] [Google Scholar]
- Pedersen O., Hjøllund E., Lindskov H. O. Insulin binding and action on fat cells from young healthy females and males. Am J Physiol. 1982 Aug;243(2):E158–E167. doi: 10.1152/ajpendo.1982.243.2.E158. [DOI] [PubMed] [Google Scholar]
- Pedersen O., Hjøllund E., Sørensen N. S. Insulin receptor binding and insulin action in human fat cells: effects of obesity and fasting. Metabolism. 1982 Sep;31(9):884–895. doi: 10.1016/0026-0495(82)90177-9. [DOI] [PubMed] [Google Scholar]
- Pernet A., Trimble E. R., Kuntschen F., Damoiseaux P., Assal J. P., Hahn C., Renold A. E. Insulin resistance in Type 1 (insulin-dependent) diabetes: dependence on plasma insulin concentration. Diabetologia. 1984 Apr;26(4):255–260. doi: 10.1007/BF00283646. [DOI] [PubMed] [Google Scholar]
- Proietto J., Nankervis A., Aitken P., Caruso G., Alford F. Glucose utilization in Type 1 (insulin-dependent) diabetes: Evidence for a defect not reversible by acute elevations of insulin. Diabetologia. 1983 Oct;25(4):331–335. doi: 10.1007/BF00253196. [DOI] [PubMed] [Google Scholar]
- Rizza R. A., Mandarino L. J., Gerich J. E. Effects of growth hormone on insulin action in man. Mechanisms of insulin resistance, impaired suppression of glucose production, and impaired stimulation of glucose utilization. Diabetes. 1982 Aug;31(8 Pt 1):663–669. doi: 10.2337/diab.31.8.663. [DOI] [PubMed] [Google Scholar]
- Smith U., Kuroda M., Simpson I. A. Counter-regulation of insulin-stimulated glucose transport by catecholamines in the isolated rat adipose cell. J Biol Chem. 1984 Jul 25;259(14):8758–8763. [PubMed] [Google Scholar]
- Soll A. H., Goldfine I. D., Roth J., Kahn C. R. Thymic lymphocytes in obese (ob-ob) mice. A mirror of the insulin receptor defect in liver and fat. J Biol Chem. 1974 Jul 10;249(13):4127–4131. [PubMed] [Google Scholar]
- Suzuki K., Kono T. Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site. Proc Natl Acad Sci U S A. 1980 May;77(5):2542–2545. doi: 10.1073/pnas.77.5.2542. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor R., Proctor S. J., James O., Clark F., George K., Alberti M. M. The relationship between human adipocyte and monocyte insulin binding. Clin Sci (Lond) 1984 Jul;67(1):139–142. doi: 10.1042/cs0670139. [DOI] [PubMed] [Google Scholar]
- Yki-Järvinen H., Koivisto V. A. Insulin sensitivity in newly diagnosed type 1 diabetics after ketoacidosis and after three months of insulin therapy. J Clin Endocrinol Metab. 1984 Sep;59(3):371–378. doi: 10.1210/jcem-59-3-371. [DOI] [PubMed] [Google Scholar]
