Oscillations in Insulin Secretion During Constant Glucose Infusion in Normal Man: Relationship to Changes in Plasma Glucose*

Shapiro, E T; Tillil, H.; Polonsky, Kenneth S.; Fang, Victor S.; Rubenstein, Arthur H.; Cauter, Eve Van

doi:10.1210/jcem-67-2-307

Cited by 120 publications

(84 citation statements)

References 27 publications

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“…These oscillations are best seen in situations of insulin stimulation, and have been observed after meal ingestion (1), during continuous enteral nutrition (2), and during intravenous glucose infusion (3). They are closely associated with similar oscillations of plasma glucose concentration.…”

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confidence: 84%

Ultradian Oscillations of Insulin Secretion in Humans

Simon¹,

Brandenberger²

2002

Diabetes

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Ultradian rhythmicity appears to be characteristic of several endocrine systems. As described for other hormones, insulin release is a multioscillatory process with rapid pulses of about 10 min and slower ultradian oscillations (50 -120 min). The mechanisms underlying the ultradian circhoral oscillations of insulin secretion rate (ISR), which arise in part from a rhythmic amplification of the rapid pulses, are not fully understood. In humans, included in the same period range is the alternation of rapid eye movement (REM) and non-REM (NREM) sleep cycles and the associated opposite oscillations in sympathovagal balance. During sleep, the glucose and ISR oscillations were amplified by about 150%, but the REM-NREM sleep cycles did not entrain the glucose and ISR ultradian oscillations. Also, the latter were not related to either the ultradian oscillations in sympathoagal balance, as inferred from spectral analysis of cardiac R-R intervals, or the plasma fluctuations of glucagon-like peptide-1 (GLP-1), an incretin hormone known to potentiate glucose-stimulated insulin. Other rhythmic physiological processes are currently being examined in relation to ultradian insulin release. Diabetes 51 (Suppl. 1):S258 -S261, 2002 I n addition to the rapid insulin pulses that recur every 5-10 min, slow and large ultradian oscillations of insulin secretion with a period range of 50 -120 min have been described in both humans and animals. These oscillations are best seen in situations of insulin stimulation, and have been observed after meal ingestion (1), during continuous enteral nutrition (2), and during intravenous glucose infusion (3). They are closely associated with similar oscillations of plasma glucose concentration. Figure 1 shows the insulin secretion rate (ISR) profile estimated from plasma C-peptide levels as proposed by Eaton (4) and the concomitant glucose profile obtained in one subject studied during continuous enteral nutrition in an experiment lasting 24 h with blood sampling at 10-min intervals. In these conditions, the mean amplitude of the oscillations reaches 50% of the mean levels for ISR and 20% for glucose. In the postprandial state, their amplitude is maximal immediately after food ingestion and then decreases progressively (1). The higher hypoglycemic effect of intermittent insulin administration, as compared with constant administration at the same average rate (5,6), suggests that, like the rapid pulses, these ultradian oscillations may have a functional significance. On the other hand, alterations in the glucose and ISR patterns have been described in patients with type 2 diabetes (7,8), and the tight coupling between glucose and ISR pulses is altered even in conditions where glucose tolerance is only minimally impaired (9). Whether these alterations, which occur early in the course of ␤-cell dysfunction (10), play a pathogenetic role in the onset of hyperglycemia is yet to be determined. Periodically modulated signals are thought to induce a larger response by the target cell than constant signals (11...

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confidence: 84%

Ultradian Oscillations of Insulin Secretion in Humans

Simon¹,

Brandenberger²

2002

Diabetes

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“…Through biological experiments it has been well-established [6,9,17,18] that insulin secretion in the pancreas oscillates on a number of different time scales, ranging from tens of seconds to more than 100 minutes. The oscillations with larger period (80-150 mins) are known as ultradian oscillations and a model developed by Sturis et al [19] (see also Keener & Sneyd [7]) provides a possible mechanism for their origin.…”

Section: Introductionmentioning

confidence: 99%

Global stability in a model of the glucose-insulin interaction with time delay

Bennett

Gourley

2004

Eur. J. Appl. Math

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A variety of models on the interaction between glucose and insulin have been suggested over the last 50 years. One, developed by Sturis et al. [19], and consisting of six nonlinear ordinary differential equations, has been widely accepted. However, the model has the disadvantage of containing auxiliary variables which have no clinical interpretation. In this paper we study an alternative model which incorporates a time delay explicitly, negating the need for the auxiliary equations. A simplifying assumption of having just one insulin compartment reduces the number of equations still further. We then study the resulting system of two differential delay equations, establishing results on positivity, boundedness, persistence and global asymptotic stability. For the latter, two quite different approaches are employed: comparison principles and Lyapunov functionals. The two approaches provide different sets of sufficient conditions for global stability, so that we investigate different regions of parameter space.

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“…circadian disruption | shift work | night work | glucose metabolism | diabetes I n healthy humans, there is a strong time-of-day variation in glucose tolerance, with a peak in the morning and a trough in the evening and night (1)(2)(3)(4)(5)(6). Understanding the underlying mechanisms of the day/night variation in glucose tolerance is important for diurnally active individuals as well as shift workers, who are at increased risk for developing type 2 diabetes (7-9).…”

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confidence: 99%

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

Morris

Yang

Garcia

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

335

330

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Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/ feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show-by using two 8-d laboratory protocols-in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic β-cell function (27% lower earlyphase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers.circadian disruption | shift work | night work | glucose metabolism | diabetes I n healthy humans, there is a strong time-of-day variation in glucose tolerance, with a peak in the morning and a trough in the evening and night (1-6). Understanding the underlying mechanisms of the day/night variation in glucose tolerance is important for diurnally active individuals as well as shift workers, who are at increased risk for developing type 2 diabetes (7-9). The endogenous circadian system and circadian misalignment (i.e., misalignment between the endogenous circadian system and 24-h environmental/behavioral cycles) have been shown to affect glucose metabolism (4,(10)(11)(12)(13)(14). However, the relative and separate importance of the endogenous circadian system and circadian misalignment-after accounting for behavioral cycle effects (including the sleep/wake, fasting/feeding, and physical inactivity/activity cycles, etc.)-on 24-h variation in glucose tolerance is not well understood.Most species have evolved an endogenous circadian timing system that optimally times physiological variations and behaviors relative to the 24-h environmental cycle (15-17). The mammalian circadian system is comp...

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Oscillations in Insulin Secretion During Constant Glucose Infusion in Normal Man: Relationship to Changes in Plasma Glucose*

Cited by 120 publications

References 27 publications

Ultradian Oscillations of Insulin Secretion in Humans

Ultradian Oscillations of Insulin Secretion in Humans

Global stability in a model of the glucose-insulin interaction with time delay

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

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