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Rapid oscillations in omental lipolysis are independent of changing insulin levels in vivo

Published on Aug 1, 2000in Journal of Clinical Investigation 12.28
· DOI :10.1172/JCI7815
Lisa Getty3
Estimated H-index: 3
,
Antonios E. Panteleon1
Estimated H-index: 1
+ 2 AuthorsRichard N. Bergman103
Estimated H-index: 103
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Abstract
Abnormal fat metabolism plays an important role in the pathogenesis of obesity-related type 2 diabetes mellitus. This study examined whether free fatty acid levels (FFAs), like insulin levels, oscillate rapidly in plasma. Peripheral and portal blood samples from dogs were assayed for FFA, glycerol, glucose, and insulin. FFA and glycerol showed correlated oscillatory profiles, with about 8 pulses/hour. Omental lipolysis was also pulsatile, with about 10 pulses/hour, and insulin levels oscillated rapidly in plasma with about 7 pulses/hour. We applied an insulin clamp, β-adrenergic blockade, or both together, to determine the driving force behind the FFA oscillation, and we analyzed our findings by approximate entropy (ApEn) for which lower values suggest regular pulses and higher values suggest disorder. Under basal conditions, ApEn was 0.3 ± 0.2. With insulin not oscillating, FFA still cycled at about 9 pulses/hour and the ApEn was 0.2 ± 0.1. In contrast, β-blockade, either in the presence or absence of an insulin clamp, removed the FFA oscillation in three of nine dogs. In the other six dogs, the oscillatory profile was unchanged, but ApEn was significantly higher than basal values, suggesting that the regularity of the profile was disrupted. These results suggest that the FFA oscillation is driven by the central nervous system, not by insulin.
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  • Citations (44)
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References50
Newest
Published on Dec 1, 1998in Diabetes 7.20
Lisa Getty3
Estimated H-index: 3
,
Marianthe Hamilton-Wessler11
Estimated H-index: 11
+ 2 AuthorsRichard N. Bergman103
Estimated H-index: 103
We examined the hindlimb lymph insulin profile during simulated intravenous glucose tolerance tests (IVGTTs) in anesthetized dogs to test the following hypotheses: 1) the biphasic insulin response to intravenous glucose can be seen as a priming bolus and a secondary infusion that effect a rapid stepwise increase in the interstitial insulin concentration and 2) the activation of glucose utilization (rate of glucose uptake [Rd]) during an IVGTT is more similar to the dynamics of the interstitial i...
38 Citations Source Cite
Published on May 1, 1997in Nature Medicine 30.64
Julio Licinio65
Estimated H-index: 65
(NIH: National Institutes of Health),
Christos S. Mantzoros103
Estimated H-index: 103
(BIDMC: Beth Israel Deaconess Medical Center)
+ 8 AuthorsJeffrey S. Flier120
Estimated H-index: 120
(BIDMC: Beth Israel Deaconess Medical Center)
Leptin communicates nutritional status to regulatory centers in the brain1,2. Because peripheral leptin influences the activity of the highly pulsatile adrenal and gonadal axes3,4, we sought to determine whether leptin levels in the blood are pulsatile. We measured circulating leptin levels every 7 minutes for 24 hours, in six healthy men, and found that total circulating leptin levels exhibited a pattern indicative of pulsatile release, with 32.0 ± 1.5 pulses every 24 hours and a pulse duration...
556 Citations Source Cite
Published on Jan 1, 1997in Diabetes 7.20
Guenther Boden63
Estimated H-index: 63
Evidence is reviewed that free fatty acids (FFAs) are one important link between obesity and insulin resistance and NIDDM. First, plasma FFA levels are elevated in most obese subjects. Second, physiological elevations in plasma FFA concentrations inhibit insulin stimulated peripheral glucose uptake in a dose-dependent manner in normal controls and in patients with NIDDM. Two possible mechanisms are identified: 1 ) a fat-related inhibition of glucose transport or phosphorylation, which appears af...
1,390 Citations Source Cite
Published on Aug 1, 1996in Diabetes 7.20
Guenther Boden63
Estimated H-index: 63
,
Xinhua Chen23
Estimated H-index: 23
,
Jean Luc Urbain1
Estimated H-index: 1
Diurnal variation in insulin sensitivity in patients with NIDDM has long been suspected but has been difficult to document mainly because of the interdependence of changes in glucose and insulin. Stable serum insulin levels during hyperglycemic clamping in patients with NIDDM in the present study provided the opportunity to examine changes in insulin sensitivity unaffected by changes in blood glucose and insulin concentrations. Six patients with NIDDM (four men and two women, BMI 33.9 ± 2.5) und...
158 Citations Source Cite
Published on May 1, 1996in Diabetes 7.20
Yun-Ping Zhou6
Estimated H-index: 6
,
Per-Olof Berggren68
Estimated H-index: 68
,
Valdemar Grill46
Estimated H-index: 46
We studied the effects of fatty acid oxidation on insulin secretion of db/db mice and underlying molecular mechanisms of these effects. At 2–3 months of age, db/db mice were markedly obese, hyperglycemic, and hyperinsulinemic. Serum free fatty acid (FFA) levels were increased in 2-month-old (1.5 ± 0.1 vs. 1.1 ± 0.1 mmol/l, P P db /+ mice serving as controls. Glucose-induced insulin release from db/db islets was markedly decreased compared with that from db /+ islets and was specifically ameliora...
80 Citations Source Cite
Published on May 1, 1996in Diabetes 7.20
Jason K. Kim68
Estimated H-index: 68
,
Jae K Wi4
Estimated H-index: 4
,
Jang H. Youn30
Estimated H-index: 30
To examine whether impairment of intracellular glucose metabolism precedes insulin resistance, we determined the time courses of changes in insulin-stimulated glucose uptake, glycolysis, and glycogen synthesis during high-fat feeding in rats. Animals were fed with a high-fat (66.5%) diet ad libitum for 0, 2, 4, 7, or 14 days ( n = 10–11 in each group) after 5 days of a low-fat (12.5%) diet. Submaximal and maximal insulin-stimulated glucose fluxes were estimated in whole body and individual skele...
73 Citations Source Cite
Published on Apr 1, 1996in Diabetes 7.20
Jason K. Kim68
Estimated H-index: 68
,
Jae K Wi4
Estimated H-index: 4
,
Jang H. Youn30
Estimated H-index: 30
The effects of elevated plasma free fatty acid (FFA) levels on insulin-stimulated whole-body and skeletal muscle glucose transport, glucose uptake, glycolysis, and glycogen synthesis were studied in conscious rats during hyperinsulinemic-euglycemic clamps with ( n = 26) or without ( n = 23) Intralipid and heparin infusion. Whole-body and skeletal muscle glucose uptake, glycolysis, and glycogen synthesis were estimated using d-[3- 3 H]glucose and 2-[ 14 C]deoxyglucose (study 1), and glucose trans...
85 Citations Source Cite
Published on Sep 1, 1995in Diabetes 7.20
Kerstin Rebrin21
Estimated H-index: 21
(SC: University of Southern California),
Garry M. Steil40
Estimated H-index: 40
(SC: University of Southern California)
+ 1 AuthorsRichard N. Bergman103
Estimated H-index: 103
(SC: University of Southern California)
Overproduction of glucose by the liver in the face of insulin resistance is a primary cause of hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM). However, mechanisms involved in control of hepatic glucose output (HGO) remain less than clear, even in normal individuals. Recent results have supported an indirect extrahepatic effect of insulin as the primary locus of insulin action to restrain HGO. One suggested extrahepatic site is the pancreatic ɑ-cell. To examine whether insulin9s...
246 Citations Source Cite
Published on Sep 1, 1995in Journal of Clinical Investigation 12.28
Guenther Boden63
Estimated H-index: 63
,
Xinhua Chen23
Estimated H-index: 23
It was the aim of this study to determine whether FFA inhibit insulin-stimulated whole body glucose uptake and utilization in patients with non-insulin-dependent diabetes. We performed five types of isoglycemic (- 11 mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin; (c) with insulin plus glycerol; (d) with saline; (e) with saline plus fat/heparin and two types of euglycemic (- 5 mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin. During these studies, we determined ra...
286 Citations Source Cite
Published on Aug 1, 1995in Diabetes 7.20
Roger H Unger112
Estimated H-index: 112
We review evidence that increased tissue levels of fatty acyl CoA cause the β-cell abnormalities of nondiabetic obesity and ultimately result in obesity-dependent diabetes. Nondiabetic obesity in Zucker rats is characterized by hypersecretion of insulin at normal fasting and subfasting glucose concentrations. This is a result of β-cell hyperplasia and increased low K m glucose usage and oxidation. These abnormalities, the hyperinsulinemia, the hyperplasia of β-cells, i.e., its in vitro equivalen...
842 Citations Source Cite
Cited By44
Newest
Published on Jan 1, 2016
Isabel R. Hsu9
Estimated H-index: 9
,
Edward Zuniga5
Estimated H-index: 5
,
Richard N. Bergman103
Estimated H-index: 103
A large number of studies have shown the existence of metabolic covalent modifications in different molecular structures, able to store biochemical information that is not encoded by the DNA. Some of these covalent mark patterns can be transmitted across generations (epigenetic changes). Recently, the emergence of Hopfield-like attractor dynamics has been observed in the self-organized enzymatic networks, which have the capacity to store functional catalytic patterns that can be correctly recove...
Published on Oct 10, 2014in PLOS ONE 2.78
Ildefonso M. De la Fuente7
Estimated H-index: 7
,
Jesús M. Cortés11
Estimated H-index: 11
(Ikerbasque)
+ 4 AuthorsLuis Martínez9
Estimated H-index: 9
(UPV/EHU: University of the Basque Country)
Biochemical energy is the fundamental element that maintains both the adequate turnover of the biomolecular structures and the functional metabolic viability of unicellular organisms. The levels of ATP, ADP and AMP reflect roughly the energetic status of the cell, and a precise ratio relating them was proposed by Atkinson as the adenylate energy charge (AEC). Under growth-phase conditions, cells maintain the AEC within narrow physiological values, despite extremely large fluctuations in the aden...
10 Citations Source Cite
Published on Jan 1, 2014
A patogenese da doenca hepatica gordurosa nao alcoolica (DHGNA) nao esta completamente esclarecida. Existem evidencias cada vez maiores de que o estresse oxidativo participa desse processo. O objetivo do presente estudo e avaliar o papel de marcadores plasmaticos de estresse oxidativo em obesos morbidos com DHGNA. Foram incluidos 43 obesos morbidos submetidos ao bypass gastrico em Y-de-Roux, com biopsia hepatica obtida durante a cirurgia. O estresse oxidativo plasmatico foi mensurado por meio da...
Published on Jan 1, 2014
Ildefonso Mtz. de la Fuente1
Estimated H-index: 1
(CSIC: Spanish National Research Council)
The self-organization of metabolic processes, such as the spontaneous dissipative formation of macromolecular structures, the functional coordination between multienzymatic complexes, and the emergence of molecular rhythms, is one of the most relevant topics in the post-genomic era. Herein, I analyze some aspects of self-organization in metabolic processes utilizing information theory to quantifying biomolecular information flows in bits, an approach that enables the visualization of emergent ef...
8 Citations Source Cite
Published on Jan 1, 2012
Deanna M. Arble9
Estimated H-index: 9
(NU: Northwestern University),
Georges Copinschi35
Estimated H-index: 35
(ULB: Université libre de Bruxelles)
+ 2 AuthorsFred W. Turek70
Estimated H-index: 70
(NU: Northwestern University)
Publisher Summary This chapter focuses on basic circadian rhythm characteristics, including the sleep-wake and feeding–fasting rhythms, as well as circadian genetics as they pertain to neuroendocrine and endocrine rhythms. A prominent feature of the neuroendocrine system is its high degree of temporal organization. An immense variety of circadian rhythms has been observed in man. Human circadian rhythms have been characterized for blood constituents, innumerable physiological variables, as well ...
3 Citations Source Cite
Published on Nov 18, 2011in PLOS ONE 2.78
Ildefonso M. De la Fuente2
Estimated H-index: 2
(CSIC: Spanish National Research Council),
Jesús M. Cortés11
Estimated H-index: 11
(UGR: University of Granada)
+ 2 AuthorsJ. Veguillas8
Estimated H-index: 8
(UPV/EHU: University of the Basque Country)
Background Experimental observations and numerical studies with dissipative metabolic networks have shown that cellular enzymatic activity self-organizes spontaneously leading to the emergence of a metabolic core formed by a set of enzymatic reactions which are always active under all environmental conditions, while the rest of catalytic processes are only intermittently active. The reactions of the metabolic core are essential for biomass formation and to assure optimal metabolic performance. T...
6 Citations Source Cite
Published on Aug 1, 2011in The Journal of Clinical Endocrinology and Metabolism 5.61
Carson C. Chow43
Estimated H-index: 43
(NIH: National Institutes of Health),
Vipul Periwal24
Estimated H-index: 24
(NIH: National Institutes of Health)
+ 5 AuthorsAnne E. Sumner28
Estimated H-index: 28
(NIH: National Institutes of Health)
Context: Obesity and diabetes are more common in African-Americans than whites. Because free fatty acids (FFA) participate in the development of these conditions, studying race differences in the regulation of FFA and glucose by insulin is essential. Objective: The objective of the study was to determine whether race differences exist in glucose and FFA response to insulin. Design: This was a cross-sectional study. Setting: The study was conducted at a clinical research center. Participants: Thi...
22 Citations Source Cite
Published on Mar 30, 2011in PLOS ONE 2.78
Darko Stefanovski17
Estimated H-index: 17
(SC: University of Southern California),
Joyce M. Richey16
Estimated H-index: 16
(SC: University of Southern California)
+ 7 AuthorsRichard N. Bergman13
Estimated H-index: 13
(SC: University of Southern California)
Objective Insulin resistance induces hyperinsulinemic compensation, which in turn maintains almost a constant disposition index. However, the signal that gives rise to the hyperinsulinemic compensation for insulin resistance remains unknown. Methods In a dog model of obesity we examined the possibility that potential early-week changes in plasma FFA, glucose, or both could be part of a cascade of signals that lead to compensatory hyperinsulinemia induced by insulin resistance. Results Hypercalor...
21 Citations Source Cite
Published on Sep 27, 2010in International Journal of Molecular Sciences 4.18
Ildefonso Martí1
Estimated H-index: 1
One of the most important goals of the postgenomic era is understanding the metabolic dynamic processes and the functional structures generated by them. Extensive studies during the last three decades have shown that the dissipative self-organization of the functional enzymatic associations, the catalytic reactions produced during the metabolite channeling, the microcompartmentalization of these metabolic processes and the emergence of dissipative networks are the fundamental elements of the dyn...
19 Citations Source Cite