Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects.
Open accessAbstract
The pattern of endogenous insulin secretion over a 24-h period, which included three mixed meals, was evaluated in 14 normal volunteers and 15 obese subjects. Insulin secretory rates were calculated from plasma C-peptide levels using individually derived C-peptide kinetic parameters and a validated open two-compartment model of peripheral C-peptide kinetics. Insulin secretion rates were consistently elevated in the obese subjects under basal conditions (11.6 +/- 1.2 vs. 5.4 +/- 0.5 nmol/h) and in the 4 h after breakfast (139 +/- 15 vs. 63 +/- 5 nmol/4 h, P less than 0.001), lunch (152 +/- 16 vs. 67 +/- 5 nmol/4 h, P less than 0.001), and dinner (145 +/- 18 vs. 65 +/- 6 nmol/4 h, P less than 0.001). In the normal subjects, basal insulin secretion represented 50 +/- 2.1% of total 24-h insulin production, insulin secretion returned to baseline between meals, and equal quantities of insulin were secreted in the 4 h after breakfast, lunch, and dinner, despite the fact that subjects consumed half the number of calories at breakfast compared to lunch and dinner. Overall glucose responses were also similar after the three meals. In contrast, the pattern of insulin secretion in obese subjects was largely normal, albeit set at a higher level. However, the insulin secretion rate after meals did not return to baseline, and the secretion rate immediately before lunch (350.5 +/- 81.9 pmol/min) and dinner (373.6 +/- 64.8 pmol/min) was considerably higher than the secretion rate immediately before breakfast (175.5 +/- 18.5 pmol/min). In these overweight subjects, the glucose response after lunch was lower than after dinner. Analysis of individual 24-h insulin secretory profiles in the normal subjects revealed that insulin secretion was pulsatile. On average 11.1 +/- 0.5 pulses were produced in each 24-h period. The most prevalent temporal distribution of postmeal secretory pulses was two pulses after breakfast and three pulses after both lunch and dinner. Insulin secretion was also pulsatile during the period without meal stimuli: 3.9 +/- 0.3 pulses occurred during the period of overnight sampling and in the 3-h period before ingestion of the breakfast meal. In the obese subjects, the number and timing of secretory pulses was similar to those of normal volunteers, although the amplitude of the pulses was significantly greater. In both groups of subjects, greater than 80% of insulin pulses were concomitant with a pulse in glucose concentration in the postmeal period. The concomitancy rate was significantly lower in the interval without the meal stimuli, averaging 47% in both groups. Thus in obesity, although hypersecretion of insulin can be documented, the temporal pattern of secretion i s largely unaltered, which suggests that the functioning beta cell mass is enhance, but normal regulatory mechanisms influencing secretion are still operative.
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Periodic oscillations in insulin secretion may contribute to the weaker correlation between QUICKI and SI Clamp in the nonobese subgroup.
“Alternatively, periodic oscillations in insulin secretion (both ultradian and 10-to 15-min periods) have been reported in healthy subjects and may also contribute to the weaker correlation in this subgroup (21,22).”
From Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity In Humans (2000) · cites this paper as [22]
The discussion (section “O Normal”; page not provided) reports ultradian insulin-secretion oscillations in normal subjects and describes rapid 10–14-minute pulsations. It does not examine QUICKI, clamp-derived insulin sensitivity, or whether oscillations weaken the correlation between them in a nonobese subgroup. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPeriodic oscillations in insulin secretion, both ultradian and 10- to 15-min periods, have been reported in healthy subjects.
“Alternatively, periodic oscillations in insulin secretion (both ultradian and 10-to 15-min periods) have been reported in healthy subjects and may also contribute to the weaker correlation in this subgroup (21,22).”
From Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity In Humans (2000) · cites this paper as [22]
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Cites
Morgan, C. R., & Lazarow, A. (1963) · Diabetes · doi:10.2337/diab.12.2.115 · Cited by 2,212 · see citing works
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 · see citing works
Self-citationThe 24-Hour Profile of Adrenocorticotropin and Cortisol in Major Depressive Illness*
Linkowski, P., MENDLEWICZ, J., Leclercq, R., Brasseur, M., Hubain, P., GOLSTEIN, J., Copinschi, G., & Cauter, E. V. (1985) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-61-3-429 · Cited by 404 · see citing works
Cyclic Oscillations of Basal Plasma Glucose and Insulin Concentrations in Human Beings
Lang, D. A., Matthews, D. R., Peto, J., & Turner, R. C. (1979) · New England Journal of Medicine · doi:10.1056/nejm197911083011903 · Cited by 400 · see citing works
Prehepatic Insulin Production in Man: Kinetic Analysis Using Peripheral Connecting Peptide Behavior*
EATON, R. P., ALLEN, R. C., SCHADE, D. S., ERICKSON, K. M., & STANDEFER, J. (1980) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-51-3-520 · Cited by 363 · see citing works
Polonsky, K. S., Licinio-Paixao, J., Given, B. D., Pugh, W., Rue, P., Galloway, J., Karrison, T., & Frank, B. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112308 · Cited by 359 · see citing works
Self-citationInsulin, Glucagon, and Glucose Exhibit Synchronous, Sustained Oscillations in Fasting Monkeys
Goodner, C. J., Walike, B. C., Koerker, D. J., Ensinck, J. W., Brown, A. C. L., Chideckel, E. W., Palmer, J. P., & Kalnasy, L. W. (1977) · Science · doi:10.1126/science.401543 · Cited by 283 · see citing works
Rizza, R. A., Gerich, J. E., Haymond, M. W., Westland, R. E., Hall, L. D., Clemens, A. H., & Service, F. J. (1980) · New England Journal of Medicine · doi:10.1056/nejm198012043032301 · Cited by 279 · see citing works
Characterization of Seven C-peptide Antisera
FABER, O. K., Binder, C., Markussen, J., Hedïng, L. G., Naithani, V. K., Kuzuya, H., BLIX, P. M., Horwitz, D. L., & Rubenstein, A. H. (1978) · Diabetes · doi:10.2337/diab.27.1.s170 · Cited by 230 · see citing works
SIMON, C., BRANDENBERGER, G., & FOLLENIUS, M. (1987) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-64-4-669 · Cited by 147 · see citing works
Rapid Oscillations in Plasma Insulin, Glucagon, and Glucose in Obese and Normal Weight Humans*
HANSEN, B. C., Jen, K. C., Pek, S., & Wolfe, R. A. (1982) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-54-4-785 · Cited by 143 · see citing works
Closed-loop and Open-loop Devices for Blood Glucose Control in Normal and Diabetic Subjects
Santiago, J. V., Clemens, A. H., Clarke, W. L., & KIPNIS, D. M. (1978) · Diabetes · doi:10.2337/diab.28.1.71 · Cited by 134 · see citing works
The Limitations to and Valid Use of C-Peptide as a Marker of the Secretion of Insulin
Polonsky, K. S., Frank, B. H., Pugh, W., Addis, A., Karrison, T. G., Meier, P., Tager, H. S., & Rubenstein, A. H. (1986) · Diabetes · doi:10.2337/diab.35.4.379 · Cited by 115 · see citing works
Self-citationIn vivo pulsatility of pancreatic islet peptides
Jaspan, J. B., Lever, E. G., Polonsky, K. S., & Cauter, E. V. (1986) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1986.251.2.e215 · Cited by 82 · see citing works
Self-citationEffects of “Jet Lag” on Hormonal Patterns. IV. Time Shifts Increase Growth Hormone Release*
GOLSTEIN, J., Cauter, E. V., Désir, D., Noël, P., Spire, J., Refetoff, S., & Copinschi, G. (1983) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-56-3-433 · Cited by 79 · see citing works
Quantitative Methods for the Analysis of Circadian and Episodic Hormone Fluctuations
Cauter, E. V. (1981) · Springer eBooks · doi:10.1007/978-94-009-8282-6_1 · Cited by 70 · see citing works
Quantitative analysis of spontaneous variations of plasma prolactin in normal man
Van Cauter, E., L'Hermite, M., Copinschi, G., Refetoff, S., Desir, D., & Robyn, C. (1981) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1981.241.5.e355 · Cited by 67 · see citing works
Intensive Conventional and Insulin Pump Therapies in Adult Type I Diabetes
Nathan, D. M., LOU, P., & Avruch, J. (1982) · Annals of Internal Medicine · doi:10.7326/0003-4819-97-1-31 · Cited by 52 · see citing works
Intensified Insulin Therapy in the Type I Diabetic Adolescent: A Controlled Trial
Schiffrin, A., Desrosiers, M., Aleyassine, H., & Belmonte, M. M. (1984) · Diabetes Care · doi:10.2337/diacare.7.2.107 · Cited by 37 · see citing works
Biphasic Patterns of Peripheral Insulin and Glucose Levels After Lunch in Normal Subjects
Robbins, D. C., Jaspan, J. B., Vasquez, B., & Cauter, E. V. (1987) · Diabetes Care · doi:10.2337/diacare.10.3.293 · Cited by 13 · see citing works
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Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., & Baskin, D. G. (2000) · Nature · doi:10.1038/35007534 · Cited by 6,451 · see citing works
Mechanisms linking obesity to insulin resistance and type 2 diabetes
Kahn, S. E., Hull, R. L., & Utzschneider, K. M. (2006) · Nature · doi:10.1038/nature05482 · Cited by 5,448 · see citing works
Katz, A., Nambi, S. S., Mather, K., Baron, A. D., Follmann, D. A., Sullivan, G., & Quon, M. J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.7.6661 · Cited by 3,831 · see citing works
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Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028 · see citing works
Ferrannini, E., Natali, A., Bell, P., Cavallo-Perin, P., Lalic, N., & Mingrone, G. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119628 · Cited by 898 · see citing works
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Patterson, R. E., & Sears, D. D. (2017) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064634 · Cited by 810 · see citing works
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Plum, L., Schubert, M., & Brüning, J. C. (2005) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2005.01.008 · Cited by 604 · see citing works
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 · see citing works
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Fonseca, V. A. (2009) · Diabetes Care · doi:10.2337/dc09-s301 · Cited by 573 · see citing works
Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus.
Polonsky, K. S., Given, B. D., Hirsch, L. J., Tillil, H., Shapiro, E. T., Beebe, C., Frank, B. H., Galloway, J. A., & Van Cauter, E. (1988) · New England Journal of Medicine · doi:10.1056/nejm198805123181903 · Cited by 567 · see citing works
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Cobelli, C., Dalla Man, C., Sparacino, G., Magni, L., De Nicolao, G., & Kovatchev, B. P. (2009) · IEEE Reviews in Biomedical Engineering · doi:10.1109/rbme.2009.2036073 · Cited by 511 · see citing works
“Deconvolution methods have been applied to estimate the secretion profile in various physiological states [89], [90] and during both intravenous and oral glucose tolerance tests [91]–[93].”
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Leahy, J. L. (2005) · Archives of Medical Research · doi:10.1016/j.arcmed.2005.01.003 · Cited by 469 · see citing works
Age-related changes in glucose metabolism, hyperglycemia, and cardiovascular risk
Chia, C. W., Egan, J. M., & Ferrucci, L. (2018) · Circulation Research · doi:10.1161/circresaha.118.312806 · Cited by 454 · see citing works
Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep
Van Cauter, E., Blackman, J. D., Roland, D., Spire, J. P., Refetoff, S., & Polonsky, K. S. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115396 · Cited by 448 · see citing works
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Boden, G., Ruiz, J., Urbain, J. L., & Chen, X. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.271.2.e246 · Cited by 261 · see citing works
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Van Cauter, E., Shapiro, E. T., Tillil, H., & Polonsky, K. S. (1992) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1992.262.4.e467 · Cited by 240 · see citing works
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Bouret, S., Levin, B. E., & Ozanne, S. E. (2015) · Physiological Reviews · doi:10.1152/physrev.00007.2014 · Cited by 157 · see citing works
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O'Meara, N. M., Sturis, J., Van Cauter, E., & Polonsky, K. S. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116560 · Cited by 132 · see citing works
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- Authors
- Polonsky, K. S., Given, B. D., & Van Cauter, E.
- Affiliations
- University of Chicago (US)
- Université Libre de Bruxelles (BE)
- ORCID
- Given, B D
- Venue
- Journal of Clinical Investigation
- Published
- 1988-02-01
- Volume
- 81
- Issue
- 2
- Pages
- 442-448
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC329589
- OpenAlex
- W2005693445
- Cited by
- 763
- References
- 20
- Citations by year
- 2026: 17 · 2025: 14 · 2024: 19 · 2023: 16 · 2022: 16 · 2021: 25 · 2020: 40 · 2019: 19 · 2018: 31 · 2017: 21 · 2016: 34 · 2015: 37 · 2014: 37 · 2013: 29 · 2012: 27
- FWCI
- 11.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- University of Chicago
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-31842, DK 20595)
- National Center for Research Resources (RR-00055)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- insulin secretion, obesity, pulsatile insulin secretion, C-peptide kinetics, postprandial insulin secretion, basal insulin secretion, glycemic response, mixed meal, insulin secretion rate, meal timing, postprandial glucose response
- MeSH terms
- Insulin Secretion, Blood Glucose, C-Peptide, Circadian Rhythm, Eating, Humans, Insulin, Obesity, Periodicity
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