Human insulin release processes measured by intraportal sampling

Pørksen, Niels; Grøfte, Thorbjørn; Greisen, Jacob; Mengel, Anette; Juhl, Claus Bogh; Veldhuis, Johannes D.; Schmitz, O.; Rössle, Martin; Vilstrup, Hendrik

doi:10.1152/ajpendo.00516.2000

Cited by 31 publications

(23 citation statements)

References 32 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Over time, b-cell function progressively declines, and eventually insulin secretion in response to glucose is nearly absent and is reduced in response to nonglucose secretagogues such as arginine (3). Insulin secretory patterns are also abnormal (4). Diurnal and ultradian oscillations in serum insulin concentration are decreased in humans early in the disease process due to impaired pulsatile insulin release (4).…”

Section: The B-cell In Type 2 Diabetesmentioning

confidence: 99%

Death and Dysfunction of Transplanted β-Cells: Lessons Learned From Type 2 Diabetes?

et al. 2013

View full text Add to dashboard Cite

β-Cell replacement by islet transplantation is a potential curative therapy for type 1 diabetes. Despite advancements in islet procurement and immune suppression that have increased islet transplant survival, graft function progressively declines, and many recipients return to insulin dependence within a few years posttransplant. The progressive loss of β-cell function in islet transplants seems unlikely to be explained by allo- and autoimmune-mediated mechanisms alone and in a number of ways resembles β-cell failure in type 2 diabetes. That is, both following transplantation and in type 2 diabetes, islets exhibit decreased first-phase glucose-stimulated insulin secretion, impaired proinsulin processing, inflammation, formation of islet amyloid, signs of oxidative and endoplasmic reticulum stress, and β-cell death. These similarities suggest common mechanisms may underlie loss of insulin production in both type 2 diabetes and islet transplantation and point to the potential for therapeutic approaches used in type 2 diabetes that target the β-cell, such as incretin-based therapies, as adjuncts for immunosuppression in islet transplantation.

show abstract

Section: The B-cell In Type 2 Diabetesmentioning

confidence: 99%

Death and Dysfunction of Transplanted β-Cells: Lessons Learned From Type 2 Diabetes?

et al. 2013

View full text Add to dashboard Cite

show abstract

“…These investigators have shown that insulin secretion during a meal has an oscillatory nature and consists of a sequence of pulses whose amplitude and frequency are modulated by glucose (the frequency of secretory bursts is ϳ6 min per pulse) (90). Also, the incretin effect appears to be mediated via the pulsatile mode of secretion (92).…”

Section: From Biphasicity To Pulsatilitymentioning

confidence: 99%

First-phase insulin secretion: does it exist in real life? Considerations on shape and function

Caumo¹,

Luzi²

2004

American Journal of Physiology-Endocrinology and Metabolism

144

115

View full text Add to dashboard Cite

To fulfill its preeminent function of regulating glucose metabolism, insulin secretion must not only be quantitatively appropriate but also have qualitative, dynamic properties that optimize insulin action on target tissues. This review focuses on the importance of the first-phase insulin secretion to glucose metabolism and attempts to illustrate the relationships between the first-phase insulin response to an intravenous glucose challenge and the early insulin response following glucose ingestion. A clear-cut first phase occurs only when the ␤-cell is exposed to a rapidly changing glucose stimulus, like the one induced by a brisk intravenous glucose administration. In contrast, peripheral insulin concentration following glucose ingestion does not bear any clear sign of biphasic shape. Coupling data from the literature with the results of a ␤-cell model simulation, a close relationship between the first-phase insulin response to intravenous glucose and the early insulin response to glucose ingestion emerges. It appears that the same ability of the ␤-cell to produce a pronounced first phase in response to an intravenous glucose challenge can generate a rapidly increasing early phase in response to the blood glucose profile following glucose ingestion. This early insulin response to glucose is enhanced by the concomitant action of incretins and neural responses to nutrient ingestion. Thus, under physiological circumstances, the key feature of the early insulin response seems to be the ability to generate a rapidly increasing insulin profile. This notion is corroborated by recent experimental evidence that the early insulin response, when assessed at the portal level with a frequent sampling, displays a pulsatile nature. Thus, even though the classical first phase does not exist under physiological conditions, the oscillatory behavior identified at the portal level does serve the purpose of rapidly exposing the liver to elevated insulin levels that, also in virtue of their up-and-down pattern, are particularly effective in restraining hepatic glucose production. insulin pulsatile secretion; mathematical models; early-phase insulin secretion IN THE PAST THREE DECADES, the relevance of insulin secretion abnormalities in the pathogenesis of type 2 diabetes mellitus have been extensively debated (32,43,86,93,97), and a consensus has been reached that, to fulfill its pivotal role in regulating glucose metabolism, insulin secretion must not only be quantitatively appropriate, but also possess qualitative, dynamic features that optimize insulin action on target tissues. In particular, increasing emphasis has been placed on the importance of the so-called first-phase insulin secretion to glucose homeostasis (27,35,55). The aim of this review is to address the following questions. Does a first-phase insulin secretion really exist in in vivo physiology? What is the relationship between the first-phase insulin response to a brisk intravenous glucose challenge and the early insulin response following glucose ingestion? What ar...

show abstract

“…n health, insulin secretion is predominantly derived from discrete insulin secretory bursts occurring at ϳ4-to 6-min intervals (1)(2)(3)(4). Increased insulin secretion in response to hyperglycemia is accomplished by amplification of insulin secretory burst mass (4 -7).…”

mentioning

confidence: 99%

Human Islet Amyloid Polypeptide Oligomers Disrupt Cell Coupling, Induce Apoptosis, and Impair Insulin Secretion in Isolated Human Islets

Ritzel¹,

Meier²,

Lin³

et al. 2007

Diabetes

Self Cite

169

152

View full text Add to dashboard Cite

Insulin secretion from the 2,000 -3,000 ␤-cells in an islet is a highly synchronized activity with discharge of insulin in coordinate secretory bursts at approximately 4-min intervals. Insulin secretion progressively declines in type 2 diabetes and following islet transplantation. Both are characterized by the presence of islet amyloid derived from islet amyloid polypeptide (IAPP). In the present studies, we examined the action of extracellular human IAPP (h-IAPP) on morphology and function of human islets. Because oligomers of h-IAPP are known to cause membrane disruption, we questioned if application of h-IAPP oligomers to human islets would lead to disruption of islet architecture (specifically cell-to-cell adherence) and a decrease in coordinate function (e.g., increased entropy of insulin secretion and diminished coordinate secretory bursts). Both hypotheses are affirmed, leading to a novel hypothesis for impaired insulin secretion in type 2 diabetes and following islet transplantation, specifically disrupted cell-to-cell adherence in islets through the actions of membrane-disrupting IAPP oligomers. Diabetes 56:65-71, 2007

show abstract

Human insulin release processes measured by intraportal sampling

Cited by 31 publications

References 32 publications

Death and Dysfunction of Transplanted β-Cells: Lessons Learned From Type 2 Diabetes?

Death and Dysfunction of Transplanted β-Cells: Lessons Learned From Type 2 Diabetes?

First-phase insulin secretion: does it exist in real life? Considerations on shape and function

Human Islet Amyloid Polypeptide Oligomers Disrupt Cell Coupling, Induce Apoptosis, and Impair Insulin Secretion in Isolated Human Islets

Contact Info

Product

Resources

About