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Assessment of hepatic insulin extraction from in vivo surrogate methods of insulin clearance measurement.

Published on Oct 1, 2018in American Journal of Physiology-endocrinology and Metabolism4.125
· DOI :10.1152/ajpendo.00344.2017
Isaac Asare-Bediako3
Estimated H-index: 3
(Cedars-Sinai Medical Center),
Rebecca L. Paszkiewicz5
Estimated H-index: 5
(Cedars-Sinai Medical Center)
+ 6 AuthorsRichard N. Bergman96
Estimated H-index: 96
(Cedars-Sinai Medical Center)
Abstract
Hyperinsulinemia, accompanied by reduced first-pass hepatic insulin extraction (FPE) and increased secretion, is a primary response to insulin resistance. Different in vivo methods are used to esti...
  • References (40)
  • Citations (3)
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References40
Newest
#1Francesca Piccinini (Cedars-Sinai Medical Center)H-Index: 3
#2David Polidori (Janssen Pharmaceutica)H-Index: 26
Last. Richard N. Bergman (Cedars-Sinai Medical Center)H-Index: 96
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African Americans (AAs) tend to have higher plasma insulin concentrations than European Americans (EAs); the increased insulin concentrations have been attributed to increased secretion and/or decreased insulin clearance by liver or other tissues. This work characterizes the contributions of hepatic versus extrahepatic insulin degradation related to ethnic differences between AAs and EAs. By using a recently developed mathematical model that uses insulin and C-peptide measurements from the insul...
21 CitationsSource
#1David Polidori (Janssen Pharmaceutica)H-Index: 26
#2Richard N. Bergman (Cedars-Sinai Medical Center)H-Index: 96
Last. Anne E. Sumner (NIH: National Institutes of Health)H-Index: 29
view all 4 authors...
Insulin clearance is a highly variable and important factor that affects circulating insulin concentrations. We developed a novel model-based method to estimate both hepatic and extrahepatic insulin clearance using plasma insulin and C-peptide profiles obtained from the insulin-modified frequently sampled intravenous glucose tolerance test. Data from 100 African immigrants without diabetes (mean age 38 years, body weight 81.7 kg, fasting plasma glucose concentration 83 mg/dL, and fasting insulin...
29 CitationsSource
#1José M. Costa-Júnior (State University of Campinas)H-Index: 6
#2Sandra Mara Ferreira (State University of Campinas)H-Index: 8
Last. Luiz F. Rezende (State University of Campinas)H-Index: 11
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Introduction Endurance training improves peripheral insulin sensitivity in the liver and the skeletal muscle, but the mechanism for this effect is poorly understood. Recently, it was proposed that insulin clearance plays a major role in both glucose homeostasis and insulin sensitivity. Therefore, our goal was to determine the mechanism by which endurance training improves insulin sensitivity and how it regulates insulin clearance in mice. Methods Mice were treadmill-trained for 4 weeks at 70–80%...
4 CitationsSource
We visualized insulin uptake in vivo across the apical membrane of the rat proximal tubule (PT) by confocal microscopy; we compared it with in vitro findings in a rat PT cell line (WKPT) using fluorescence microscopy and flow cytometry. Surface tubules were observed in vivo with a 633-nm single laser-illuminated real-time video-rate confocal scanning microscope in upright configuration for optical sectioning below the renal capsule. Fields were selected containing proximal and distal tubules; Cy...
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#1Kamyar Kalantar-Zadeh (UCLA: University of California, Los Angeles)H-Index: 96
#2Stephen F. Derose (KP: Kaiser Permanente)H-Index: 21
Last. Csaba P. Kovesdy (UVA: University of Virginia)H-Index: 70
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Many individuals with diabetic nephropathy, the leading cause of chronic kidney disease (CKD) in the United States, progress to stage 5 of CKD and undergo maintenance dialysis treatment. Recent data indicate that in up to one third of diabetic dialysis patients with a presumptive diagnosis of diabetic nephropathy, glycemic control improves spontaneously with the progression of CKD, loss of residual renal function, and the initiation of dialysis therapy, leading to normal-to-low hemoglobin A1c (
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#1Emma M. EgglestonH-Index: 2
#2Linda A. JahnH-Index: 18
Last. Eugene J. BarrettH-Index: 54
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OBJECTIVE— Transport of insulin from the central circulation into muscle is rate limiting for the stimulation of glucose metabolism. By recruiting muscle microvasculature, insulin may promote its own movement into muscle interstitium. We tested whether in humans, as in the rat, insulin exerts an early action to recruit microvasculature within skeletal muscle. We further hypothesized that expansion of the microvascular volume of muscle would enhance muscle insulin clearance. RESEARCH DESIGN AND M...
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During insulin resistance, glucose homeostasis is maintained by an increase in plasma insulin via increased secretion and/or decreased first-pass hepatic insulin extraction. However, the relative importance of insulin secretion vs. clearance to compensate for insulin resistance in obesity has yet to be determined. This study utilizes the fat-fed dog model to examine longitudinal changes in insulin secretion and first-pass hepatic insulin extraction during development of obesity and insulin resis...
52 CitationsSource
#1Juris J. Meier (UCLA: University of California, Los Angeles)H-Index: 58
Last. Peter C. Butler (UCLA: University of California, Los Angeles)H-Index: 65
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In health, insulin is secreted in discrete pulses into the portal vein, and the regulation of the rate of insulin secretion is accomplished by modulation of insulin pulse mass. Several lines of evidence suggest that the pattern of insulin delivery by the pancreas determines hepatic insulin clearance. In previous large animal studies, the amplitude of insulin pulses was related to the extent of insulin clearance. In humans (and in large animals), the amplitude of insulin oscillations is ∼100-fold...
161 CitationsSource
#1Stella P. KimH-Index: 18
#2Martin EllmererH-Index: 19
Last. Richard N. BergmanH-Index: 96
view all 4 authors...
Obesity is highly correlated with insulin resistance and the development of type 2 diabetes. Insulin resistance will result in a decrease in insulin's ability to stimulate glucose uptake into peripheral tissue and will suppress glucose production by the liver. However, the development of peripheral and hepatic insulin resistance relative to one another in the context of obesity-associated insulin resistance is not well understood. To examine this phenomena, we used the moderate fat-fed dog model...
164 CitationsSource
#1Filip Braet (Free University of Brussels)H-Index: 35
#2Eddie Wisse (Free University of Brussels)H-Index: 41
This review provides a detailed overview of the current state of knowledge about the ultrastructure and dynamics of liver sinusoidal endothelial fenestrae. Various aspects of liver sinusoidal endothelial fenestrae regarding their structure, origin, species specificity, dynamics and formation will be explored. In addition, the role of liver sinusoidal endothelial fenestrae in relation to lipoprotein metabolism, fibrosis and cancer will be approached.
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Cited By3
Newest
Source
#1Richard N. Bergman (Cedars-Sinai Medical Center)H-Index: 96
#2Francesca Piccinini (Cedars-Sinai Medical Center)H-Index: 3
Last. Marilyn Ader (Cedars-Sinai Medical Center)H-Index: 28
view all 5 authors...
There is wide variance among individuals in the fraction of insulin cleared by the liver (20% to 80%). Hepatic insulin clearance is 67% lower in African Americans than European Americans. Clearance is also lower in African American children 7–13 years of age. Lower hepatic insulin clearance will result in peripheral hyperinsulinemia: this exacerbates insulin resistance, which stresses the β-cells, possibly resulting in their ultimate failure and onset of type 2 diabetes. We hypothesize that lowe...
1 CitationsSource
#1Richard N. Bergman (Cedars-Sinai Medical Center)H-Index: 96
#2Francesca Piccinini (Cedars-Sinai Medical Center)H-Index: 3
Last. Marilyn Ader (Cedars-Sinai Medical Center)H-Index: 28
view all 7 authors...
2 CitationsSource