IGF-I inhibits burst mass of pulsatile insulin secretion at supraphysiological and low IGF-I infusion rates

Pørksen, Niels; Hussain, Mehboob A.; Bianda, T; Nyholm, Birgit; Christiansen, Jens Sandahl; Butler, Peter C.; Veldhuis, Johannes D.; Froesch, E. R.; Schmitz, Ole

doi:10.1152/ajpendo.1997.272.3.e352

Cited by 23 publications

(20 citation statements)

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“…Because the nature of insulin secretion is pulsatile (4) and the contribution by secretory bursts per se may be the major mechanism regulating release in fasting (20,21), inhibited (16,20), and stimulated (19,22) states, we sought to characterize in vivo insulin secretion in humans by use of the portal vein sampling procedure combined with a deconvolution technique. Similar sampling protocols have previously been employed in humans (27) with the use of discrete pulse detection algorithms to identify significant oscillations in insulin concentrations and, recently (25), with the use of methods similar to those herein and reporting similar changes upon stimulation with hyperglycemia.…”

Section: Discussionmentioning

confidence: 99%

“…In both species, the overall contribution of pulsatile insulin secretion to total insulin release is Ն70-75%. Furthermore, the mechanisms underlying changes in overall insulin secretion after stimulation (18,19) and inhibition (16,20) are exerted principally via modulations in the pulsatile component of insulin secretion, with changes in the mass and/or frequency of insulin-secretory bursts. It therefore appears that the pulsatile pattern is physiologically integrated to overall ␤-cell secretory performance, as underscored by impaired pulsatility in non-insulindependent diabetes mellitus (NIDDM) (6) and glucoseintolerant first-degree relatives of NIDDM patients (11) and by a defective release process in glucosetolerant first-degree relatives of NIDDM patients (24).…”

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confidence: 99%

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Human insulin release processes measured by intraportal sampling

Pørksen¹,

Grøfte

Greisen

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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. Human insulin release processes measured by intraportal sampling. Am J Physiol Endocrinol Metab 282: E695-E702, 2002; 10.1152/ajpendo.00516.2000.-Insulin is secreted as a series of punctuated secretory bursts superimposed on variable basal insulin release. The contribution of these secretory bursts to overall insulin secretion has been estimated on the basis of peripheral vein sampling in humans to encompass Ն75% of overall insulin release. A similar contribution of the pulsatile mode of release was inferred in a canine model by use of portal vein sampling. The primary regulation of insulin secretion is through perturbation of the mass and frequency of these secretory bursts. The mode of delivery of insulin into the circulation seems important for insulin action; therefore, physiological conditions that alter the pattern of insulin release may affect insulin action through this mechanism. Transhepatic intraportal shunt in humans may provide access to portal vein samples, thus potentially improving the sensitivity of detecting and quantitating the frequency, mass, and amplitude of secretory bursts along with basal release and the regularity of these variables. To establish the insulin-secretory mechanism in nondiabetic humans by the use of portal vein sampling, we here assessed the mass, frequency, amplitude, and overall contribution of pulsatile insulin secretion by deconvolution analysis of portal vein insulin profiles. We find that, in nondiabetic humans fasted overnight, the portal vein insulin concentration oscillates at a periodicity of 4.1 Ϯ 0.2 min/pulse and with secretory peak amplitudes averaging 660% of basal (interpulse) release. The frequency was confirmed by spectral and autocorrelation analyses. The punctuated insulin-secretory bursts partially overlap and are responsible for the majority (70 Ϯ 4%) of insulin release. After ingestion of a mixed meal, the insulin release was increased through amplification of the secretory burst mass (507 Ϯ 104 vs. 1,343 Ϯ 211 pmol ⅐ l Ϫ1 ⅐ min Ϫ1 , P Ͻ 0.001), whereas frequency (4.4 Ϯ 0.2 vs. 4.3 Ϯ 0.2, P ϭ 0.86) and basal secretion (62 Ϯ 14 vs. 91 Ϯ 22 pmol ⅐ l Ϫ1 ⅐ min Ϫ1 , P ϭ 0.33) were unaffected. One subject with diabetes and cirrhosis had a similar insulin-secretory pattern, whereas a subject with insulin-dependent diabetes mellitus and minimal insulin release had preserved pulsatile release. A single subject was entrained to show agreement between entrained frequency and portal vein insulin oscillations. We conclude that insulin release in the human portal vein occurs at a mean periodicity of 4.4 Ϯ 0.2 min with a high signal-to-noise ratio (pulse amplitude 660% of basal). The impact of noise on the detected high frequency cannot be excluded.C-peptide; oscillations; cirrhosis; secretion; diabetes INSULIN IS SECRETED in a pulsatile manner (4), resulting in high-frequency insulin concentration oscillations in the peripheral circulation. These high-frequency oscillations are apparently caused by interislet coordinate insulin-secretory bursts at a periodicity...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Human insulin release processes measured by intraportal sampling

Pørksen¹,

Grøfte

Greisen

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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“…The pituitary-islet interaction is represented by insulin-like growth factor-1 (IGF-1) with the presence of IGF-1 receptors on ␤-cells. In humans, IGF-1 is shown to act on insulin secretion via inhibition of the secretory burst mass, and with no impact on secretory burst frequency (28), which is analogous to the effects of IGF-1 on pulsatile secretion of growth hormone (137). Impact of drugs on insulin pulsatility.…”

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confidence: 91%

Pulsatile Insulin Secretion: Detection, Regulation, and Role in Diabetes

et al. 2002

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Insulin concentrations oscillate at a periodicity of 5-15 min per oscillation. These oscillations are due to coordinate insulin secretory bursts, from millions of islets. The generation of common secretory bursts requires strong within-islet and within-pancreas coordination to synchronize the secretory activity from the ␤-cell population. The overall contribution of this pulsatile mechanism dominates and accounts for the majority of insulin release. This review discusses the methods involved in the detection and quantification of periodicities and individual secretory bursts. The mechanism by which overall insulin secretion is regulated through changes in the pulsatile component is discussed for nerves, metabolites, hormones, and drugs. The impaired pulsatile secretion of insulin in type 2 diabetes has resulted in much focus on the impact of the insulin delivery pattern on insulin action, and improved action from oscillatory insulin exposure is demonstrated on liver, muscle, and adipose tissues. Therefore, not only is the dominant regulation of insulin through changes in secretory burst mass and amplitude, but the changes may affect insulin action. Finally, the role of impaired pulsatile release in early type 2 diabetes suggests a predictive value of studies on insulin pulsatility in the development of this disease. Diabetes 51 (Suppl. 1): S245-S254, 2002

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“…Substrates (glucose), hormones (glucagon-like peptide [GLP]-1, somatostatin, and IGF-1), and antidiabetic compounds that regulate insulin secretion seem to exert their actions primarily via modulation of insulin secretory burst mass rather than frequency (11)(12)(13)(14)(15)(16)(17)(18)(19). Despite the widespread clinical use of insulin secretagogues in the treatment of type 2 diabetes, the influence of these antidiabetic drugs on the oscillatory pattern of insulin release has been elucidated only sparingly in diabetic humans (12).…”

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confidence: 99%

Acute and Short-Term Administration of a Sulfonylurea (Gliclazide) Increases Pulsatile Insulin Secretion in Type 2 Diabetes

et al. 2001

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The high-frequency oscillatory pattern of insulin release is disturbed in type 2 diabetes. Although sulfonylurea drugs are widely used for the treatment of this disease, their effect on insulin release patterns is not well established. The aim of the present study was to assess the impact of acute treatment and 5 weeks of sulfonylurea (gliclazide) treatment on insulin secretory dynamics in type 2 diabetic patients. To this end, 10 patients with type 2 diabetes (age 53 ؎ 2 years, BMI 27.5 ؎ 1.1 kg/m 2 , fasting plasma glucose 9.8 ؎ 0. ; placebo, 5.9 ؎ 0.9 vs. 7.2 ؎ 0.9 pmol ⅐ l -1 ⅐ pulse -1 , P ‫؍‬ 0.03; 5 weeks-elevated: gliclazide vs. placebo, 12.2 ؎ 2.5 vs. 9.4 ؎ 2.1 pmol ⅐ l -1 ⅐ pulse -1 , P ‫؍‬ 0.016). The frequency and regularity of insulin pulses were not modified significantly by the antidiabetic therapy. There was, however, a correlation between individual values for the acute improvement of regularity, as measured by ApEn, and the decrease in fasting plasma glucose during shortterm (5-week) gliclazide treatment (r ‫؍‬ 0.74, P ‫؍‬ 0.014, and r ‫؍‬ 0.77, P ‫؍‬ 0.009, for fine and coarse ApEn, respectively). In conclusion, the sulfonylurea agent gliclazide augments insulin secretion by concurrently increasing pulse mass and basal insulin secretion without changing secretory burst frequency or regularity. The data suggest a possible relationship between the improvement in short-term glycemic control and the acute improvement of regularity of the in vivo insulin release process.

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IGF-I inhibits burst mass of pulsatile insulin secretion at supraphysiological and low IGF-I infusion rates

Cited by 23 publications

References 14 publications

Human insulin release processes measured by intraportal sampling

Human insulin release processes measured by intraportal sampling

Pulsatile Insulin Secretion: Detection, Regulation, and Role in Diabetes

Acute and Short-Term Administration of a Sulfonylurea (Gliclazide) Increases Pulsatile Insulin Secretion in Type 2 Diabetes

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