The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Longitudinal compensation for fat-induced insulin resistance includes reduced insulin clearance and enhanced beta-cell response.
Abstract
Central adiposity is highly correlated with insulin resistance, which is an important risk factor for type 2 diabetes and other chronic diseases. However, in normal individuals, central adiposity can be tolerated for many years without development of impaired glucose tolerance or diabetes. Here we examine longitudinally the mechanisms by which glucose tolerance can be maintained in the face of substantial insulin resistance. Normal dogs were fed a diet enriched with moderate amounts of fat (2 g x kg(-1) x day(-1)), similar to that seen in modern "cafeteria" diets, and the time course of metabolic changes in these animals was examined over 12 weeks. Trunk adiposity as assessed by magnetic resonance imaging increased from 12 to 19%, but body weight remained unchanged. Insulin sensitivity (SI) as determined by frequently sampled intravenous glucose tolerance tests was measured over a 12-week period. SI decreased 35% by week 1 and remained impaired for the entire 12 weeks. Intravenous glucose tolerance was reduced transiently for 1 week, recovered to baseline, and then again began to decline after 8 weeks. First-phase insulin response began to increase after week 2, peaked by week 6 (190% of basal), and then declined. The increase in insulin response was due partially to enhanced beta-cell function (22%) but due also to an approximately 50% reduction in insulin clearance. This compensation by insulin clearance was also confirmed with insulin clamps performed in fat-fed versus control dogs. The present study confirms the ability of the normal individual to compensate for fat-induced insulin resistance by enhanced insulin response, such that the product of insulin sensitivity x secretion is little changed. However, the compensation is due as much to reduced insulin clearance as increased beta-cell sensitivity to glucose. Reduced hepatic extraction of insulin may be the first line of defense providing a higher proportion of secreted insulin to the periphery and sparing the beta-cells during compensation for the insulin-resistant state.
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Cites
Lillioja, S., Mott, D. M., Spraul, M., Ferraro, R., Foley, J. E., Ravussin, E., Knowler, W. C., Bennett, P. H., & Bogardus, C. (1993) · New England Journal of Medicine · doi:10.1056/nejm199312303292703 · Cited by 1,508
Kahn, S. E., Prigeon, R. L., McCulloch, D. K., Boyko, E. J., Bergman, R. N., Schwartz, M. W., Neifing, J. L., Ward, W. K., Beard, J. C., & Palmer, J. P. (1993) · Diabetes · doi:10.2337/diab.42.11.1663 · Cited by 1,405
Self-citationFerrannini, E., Natali, A., Bell, P., Cavallo-Perin, P., Lalic, N., & Mingrone, G. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119628 · Cited by 898
Impaired Glucose Tolerance as a Disorder of Insulin Action
Lillioja, S., Mott, D. M., Howard, B. V., Bennett, P. H., Yki-Järvinen, H., Freymond, D., Nyomba, B. L., Zurlo, F., Swinburn, B., & Bogardus, C. (1988) · New England Journal of Medicine · doi:10.1056/nejm198805123181901 · Cited by 578
Quantitative study of insulin secretion and clearance in normal and obese subjects
Polonsky, K. S., Given, B. D., Hirsch, L., Shapiro, E. T., Tillil, H., Beebe, C., Galloway, J. A., Frank, B. H., Karrison, T., & Van Cauter, E. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113338 · Cited by 444
The natural history of impaired glucose tolerance in the Pima Indians
Saad, M. F., Knowler, W. C., Pettitt, D. J., Nelson, R. G., Mott, D. M., & Bennett, P. H. (1988) · New England Journal of Medicine · doi:10.1056/nejm198812083192302 · Cited by 413
Splanchnic insulin metabolism in obesity. Influence of body fat distribution.
Peiris, A. N., Mueller, R. A., Smith, G. A., Struve, M. F., & Kissebah, A. H. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112758 · Cited by 346
Obesity and insulin resistance: Lessons learned from the Pima indians
Lillioja, S., & Bogardus, C. (1988) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610040508 · Cited by 203
Alterations in immunoreactive proinsulin and insulin clearance induced by weight loss in NIDDM
Polonsky, K. S., Gumbiner, B., Ostrega, D., Griver, K., Tager, H., & Henry, R. R. (1994) · Diabetes · doi:10.2337/diab.43.7.871 · Cited by 56
Cited by
Free Fatty Acids and Pathogenesis of Type 2 Diabetes Mellitus
BERGMAN, R., & ADER, M. (2000) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(00)00323-4 · Cited by 622
Self-citationKabir, M., Catalano, K. J., Ananthnarayan, S., Kim, S. P., Van Citters, G. W., Dea, M. K., & Bergman, R. N. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00203.2004 · Cited by 327
Self-citationFree fatty acid-induced hepatic insulin resistance: a potential role for protein kinase C-δ
Lam, T. K. T., Yoshii, H., Haber, C. A., Bogdanovic, E., Lam, L., Fantus, I. G., & Giacca, A. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00038.2002 · Cited by 195
The Epidemiology of Central Fat Distribution in Relation to Disease
Pi-Sunyer, F. X. (2004) · Nutrition Reviews · doi:10.1111/j.1753-4887.2004.tb00081.x · Cited by 153
Luscombe-Marsh, N. D., Noakes, M., Wittert, G. A., Keogh, J. B., Foster, P., & Clifton, P. M. (2005) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.4.762 · Cited by 145
Metadata
- Authors
- Mittelman, S. D., Van Citters, G. W., Kim, S. P., Davis, D. A., Dea, M. K., Hamilton-Wessler, M., & Bergman, R. N.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2000-12-01
- Volume
- 49
- Issue
- 12
- Pages
- 2116-2125
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2130001481
- Cited by
- 200
- References
- 9
- FWCI
- 10.24
- Type
- journal article
- Language
- en
- Open access
- closed
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- Mittelman, S. D., Van Citters, G. W., Kim, S. P., Davis, D. A., Dea, M. K., Hamilton-Wessler, M., & Bergman, R. N. (2000). Longitudinal compensation for fat-induced insulin resistance includes reduced insulin clearance and enhanced beta-cell response. Diabetes. https://doi.org/10.2337/diabetes.49.12.2116
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