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Fatty acids, lipotoxicity and insulin secretion

Published on Jan 21, 1999in Diabetologia 7.11
· DOI :10.1007/s001250051130
J. D. McGarry2
Estimated H-index: 2
(UTSW: University of Texas Southwestern Medical Center),
R. L. Dobbins1
Estimated H-index: 1
(UTSW: University of Texas Southwestern Medical Center)
Cite
Abstract
tant energy source for most body tissues, particularly during periods of food deprivation, but recent evidence suggests that these same molecules subserve a much broader function in whole body fuel homeostasis by virtue of their ability to act as potent signalling entities in a variety of cellular processes. One such auxiliary role of NEFA is to heighten the responsiveness of the pancreatic beta cell to a variety of insulin secretagogues. Importantly, this fatty acid-beta cell interaction, though designed by nature for physiological purposes, can, under certain circumstances, take on a pathophysiological dimension. Some new developments surrounding this Jekyll and Hyde character of fatty acids will be reviewed briefly below.
  • References (75)
  • Citations (487)
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References75
Newest
Published on Oct 1, 1998in Diabetes 7.20
Robert L. Dobbins21
Estimated H-index: 21
(UTSW: University of Texas Southwestern Medical Center),
M W Chester3
Estimated H-index: 3
(UTSW: University of Texas Southwestern Medical Center)
+ 2 AuthorsDaniel T. Stein23
Estimated H-index: 23
(UTSW: University of Texas Southwestern Medical Center)
In the fasted rat, efficient glucose-stimulated insulin secretion (GSIS) is absolutely dependent on an elevated level of circulating free fatty acids (FFAs). To determine if this is also true in humans, nonobese volunteers were fasted for 24 h (n = 5) or 48 h (n = 5), after which they received an infusion of either saline or nicotinic acid (NA) to deplete their plasma FFA pool, followed by an intravenous bolus of glucose. NA treatment resulted in a fall in basal insulin concentrations of 35 and ...
189 Citations Source Cite
Published on Oct 1, 1998in Diabetes 7.20
Guenther Boden63
Estimated H-index: 63
,
Xinhua Chen23
Estimated H-index: 23
,
Nayyar Iqbal21
Estimated H-index: 21
The objective of this study was to determine whether basal plasma free fatty acid (FFA) concentrations affect basal insulin secretion rates (ISRs). Effects of FFA levels on basal ISRs were evaluated by lowering basal plasma FFA levels with nicotinic acid (NA) (100-150 mg p.o., q 30 min x 4 h) in type 2 diabetic patients and in normal volunteers. Lowering of FFAs (from approximately 600 to approximately 100 micromol/l) lowered ISRs in type 2 diabetic patients during isoglycemic clamping (from 139...
111 Citations Source Cite
Published on Jul 1, 1998in Diabetes 7.20
I Cusin11
Estimated H-index: 11
,
K E Zakrzewska6
Estimated H-index: 6
+ 5 AuthorsFrançoise Rohner-Jeanrenaud48
Estimated H-index: 48
Continuous (4 days) intracerebroventricular leptin infusion (12 microg/day) was performed in lean rats, and its hormonometabolic effects were determined. Intracerebroventricular leptin administration did not result in leakage of the hormone into the peripheral circulation. Thus, its effects were elicited by its presence within the central nervous system. Intracerebroventricular leptin infusion produced marked decreases in food intake and body weight gain relative to vehicle-infused fed ad libitu...
177 Citations Source Cite
Published on Jun 1, 1998in Journal of Clinical Investigation 12.28
Robert L. Dobbins21
Estimated H-index: 21
(UTSW: University of Texas Southwestern Medical Center),
M W Chester3
Estimated H-index: 3
(UTSW: University of Texas Southwestern Medical Center)
+ 3 AuthorsJ. D. McGarry48
Estimated H-index: 48
(UTSW: University of Texas Southwestern Medical Center)
Lowering of the plasma FFA level in intact fasted rats by infusion of nicotinic acid (NA) caused essentially complete ablation of insulin secretion (IS) in response to a subsequent intravenous bolus of arginine, leucine, or glibenclamide (as previously found using glucose as the beta-cell stimulus). However, in all cases, IS became supranormal when a high FFA level was maintained by co-infusion of lard oil plus heparin. Each of these secretagogues elicited little, if any, IS from the isolated, p...
122 Citations Source Cite
Published on May 1, 1998in Journal of Clinical Investigation 12.28
Ye Qi Liu7
Estimated H-index: 7
,
Keith Tornheim1
Estimated H-index: 1
,
Jack L. Leahy23
Estimated H-index: 23
Diabetic states are characterized by a raised serum/islet level of long chain fatty acids and a lowered ED50 for glucose-induced insulin secretion. Prolonged culture (> 6 h) of islets with long chain fatty acids replicates the basal insulin hypersecretion. We examined this effect in rat islets cultured for 24 h with 0.25 mM oleate. Insulin secretion at 2.8 mM glucose was doubled in combination with a 60% lowered islet content of glucose-6-phosphate (G6P). Investigation of the lowered G6P showed:...
47 Citations Source Cite
Michio Shimabukuro39
Estimated H-index: 39
(UTSW: University of Texas Southwestern Medical Center),
Y An-Tingzhou20
Estimated H-index: 20
(UTSW: University of Texas Southwestern Medical Center)
+ 1 AuthorsRoger H Unger112
Estimated H-index: 112
Like obese humans, Zucker diabetic fatty (ZDF) rats exhibit early β cell compensation for insulin resistance (4-fold β cell hyperplasia) followed by decompensation (>50% loss of β cells). In prediabetic and diabetic ZDF islets, apoptosis measured by DNA laddering is increased 3- and >7-fold, respectively, compared with lean ZDF controls. Ceramide, a fatty acid-containing messenger in cytokine-induced apoptosis, was significantly increased (P 1 mM) in prediabetic and diabetic ZDF rats; therefore,...
940 Citations Source Cite
Published on Mar 1, 1998in Journal of Clinical Investigation 12.28
L C Bollheimer2
Estimated H-index: 2
,
Robert H. Skelly4
Estimated H-index: 4
+ 2 AuthorsChristopher J. Rhodes78
Estimated H-index: 78
The pancreatic beta cell normally maintains a stable balance among insulin secretion, insulin production, and insulin degradation to keep optimal intracellular stores of the hormone. Elevated levels of FFA markedly enhance insulin secretion; however, the effects of FFA on insulin production and intracellular stores remain unclear. In this study, twofold elevation in total circulating FFA effected by infusion of lard oil and heparin into rats for 6 h under normoglycemic conditions resulted in a m...
227 Citations Source Cite
Published on Mar 1, 1998in Diabetes 7.20
A Pick2
Estimated H-index: 2
,
J Clark1
Estimated H-index: 1
+ 4 AuthorsKenneth S. Polonsky86
Estimated H-index: 86
To define the mechanisms involved in the evolution of diabetes in the Zucker diabetic fatty (ZDF) rat, beta-cell mass and replication rates were determined by immunochemistry, point-counting morphometry, and 6-h 5-bromo-29-deoxyuridine (BrdU) incorporation. The beta-cell mass in 5- to 7-week-old prediabetic ZDF rats (4.3 +/- 0.06 mg) was similar to age-matched insulin-resistant Zucker fatty (ZF) rats (3.7 +/- 0.05 mg) and greater than that in Zucker lean control (ZLC) rats (1.9 +/- 0.3, P
464 Citations Source Cite
Published on Jan 1, 1998in Cellular Signalling 3.39
Shaoying Zhang7
Estimated H-index: 7
(Purdue University),
Ki-Han Kim28
Estimated H-index: 28
(Purdue University)
Abstract The current model of the nutrient sensing mechanism in pancreatic β-cells implies that malonyl-CoA plays a key role. According to this hypothesis, glucose activation of acetyl-CoA carboxylase triggers a rapid production of malonyl-CoA which inhibits carnitine palmitoyltransferase 1 and the importation of fatty acyl-CoA into the mitochondria for oxidation. The increase in cytosolic long chain fatty acyl-CoA leads to the exocytosis of insulin by a mechanism which has not yet been clearly ...
47 Citations Source Cite
Published on Nov 1, 1997in Diabetes 7.20
Nicholas D. Oakes21
Estimated H-index: 21
(Garvan Institute of Medical Research),
Gregory J. Cooney53
Estimated H-index: 53
(RPA: Royal Prince Alfred Hospital)
+ 2 AuthorsEdward W. Kraegen66
Estimated H-index: 66
(Garvan Institute of Medical Research)
To elucidate cellular mechanisms of insulin resistance induced by excess dietary fat, we studied conscious chronically high-fat–fed (HFF) and control chow diet-fed rats during euglycemic-hyperinsulinemic (560 pmol/1 plasma insulin) clamps. Compared with chow diet feeding, fat feeding significantly impaired insulin action (reduced whole body glucose disposal rate, reduced skeletal muscle glucose metabolism, and decreased insulin suppressibility of hepatic glucose production [HGP]). In HFF rats, h...
353 Citations Source Cite
Cited By487
Newest
Published on Jun 1, 2019in Biotechnology and Bioprocess Engineering 1.44
Seulmini Goh (IIT: Inha University), Dongjoo Kim2
Estimated H-index: 2
(IIT: Inha University)
+ 2 AuthorsSoonjo Kwon6
Estimated H-index: 6
(IIT: Inha University)
Diabetes mellitus is a chronic, progressive disease that has lasting effects on several organs and tissues. In addition, high glucose levels, high triglyceride and high cholesterol levels increase patient health problems. In this study, we investigated natural materials that can alleviate diabetes symptoms or prevent its onset and assessed extracts of bamboo stem, which has been known for centuries as a functional food. Mouse 3T3-L1 cells were induced to differentiate by adding a mixture of dexa...
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Published on May 14, 2019in Islets 1.88
Iok Teng Kuok2
Estimated H-index: 2
(UW: University of Washington),
Austin M. Rountree6
Estimated H-index: 6
(UW: University of Washington)
+ 1 AuthorsIan R. Sweet29
Estimated H-index: 29
(UW: University of Washington)
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Published on Apr 1, 2019in Biochimica et Biophysica Acta 3.79
James P. C. Coverdale4
Estimated H-index: 4
(Warw.: University of Warwick),
Siavash Khazaipoul3
Estimated H-index: 3
(St And: University of St Andrews)
+ 2 AuthorsClaudia A. Blindauer27
Estimated H-index: 27
(Warw.: University of Warwick)
This work was supported by the Leverhulme Trust (grant ref. RPG-2017-214), BBSRC (grant ref. BB/J006467/1) and the British Heart Foundation (grant refs. PG/15/9/31270 and FS/15/42/31556).
1 Citations Source Cite
Jan Weis15
Estimated H-index: 15
(Uppsala University Hospital),
Håkan Ahlström49
Estimated H-index: 49
(Uppsala University Hospital),
Olle Korsgren59
Estimated H-index: 59
(Uppsala University Hospital)
Objective To estimate pancreas graft relaxation times and concentrations of total fat, and the intracellular lipids of non-adipose pancreatic cells (NAPC) using proton (1H) magnetic resonance spectroscopy (MRS) during cold preservation.
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Published on Mar 1, 2019in Biofactors 3.60
Ericka Moreno‐Méndez (UNAM: National Autonomous University of Mexico), Alain Hernández-Vázquez3
Estimated H-index: 3
(UNAM: National Autonomous University of Mexico),
Cristina Fernández Mejía14
Estimated H-index: 14
(UNAM: National Autonomous University of Mexico)
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Published on Dec 1, 2018in Scientific Reports 4.01
Emi Ogata1
Estimated H-index: 1
(Fukushima Medical University),
Koichi Asahi13
Estimated H-index: 13
+ 13 AuthorsIchiei Narita31
Estimated H-index: 31
Although fasting plasma glucose levels <70 mg/dL are associated with a high incidence of cardiovascular disease (CVD), whether there is any risk of new-onset diabetes mellitus owing to fasting plasma glucose at this range has not been clarified. We measured the odds ratio (OR) of new-onset diabetes mellitus relative to fasting plasma glucose levels at various ranges in a nation-wide Japanese population with and without CVD history. Of 186,749 participants without diabetes in 2008, 171,408 had no...
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Published on Nov 1, 2018in Biomedicine & Pharmacotherapy 3.74
Biplab Giri4
Estimated H-index: 4
(University of Gour Banga),
Sananda Dey2
Estimated H-index: 2
(University of Gour Banga)
+ 3 AuthorsSandeep Kumar Dash1
Estimated H-index: 1
(University of Gour Banga)
Abstract Chronic exposure of glucose rich environment creates several physiological and pathophysiological changes. There are several pathways by which hyperglycemia exacerbate its toxic effect on cells, tissues and organ systems. Hyperglycemia can induce oxidative stress, upsurge polyol pathway, activate protein kinase C (PKC), enhance hexosamine biosynthetic pathway (HBP), promote the formation of advanced glycation end-products (AGEs) and finally alters gene expressions. Prolonged hyperglycem...
8 Citations Source Cite
Published on Aug 1, 2018in Journal of Chromatography B 2.81
Wenyue Jiang2
Estimated H-index: 2
(JLU: Jilin University),
Lihui Si1
Estimated H-index: 1
(JLU: Jilin University)
+ 8 AuthorsZhongying Liu6
Estimated H-index: 6
(JLU: Jilin University)
Abstract Fenugreek is a well-known medicinal plant used for treatment of diabetes. In this study, the antidiabetic effect of fenugreek flavonoids was investigated by metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Fenugreek flavonoids were purified using polyamide resin and D101 macroporous adsorption resin, characterized by UPLC-Q-TOF-MS, and administered to streptozotocin (STZ)-induced diabetic rats for 28 ...
1 Citations Source Cite
Published on Jan 1, 2018in Lab on a Chip 6.91
Basel Bandak2
Estimated H-index: 2
(FSU: Florida State University),
Lian Yi6
Estimated H-index: 6
(FSU: Florida State University),
Michael G. Roper22
Estimated H-index: 22
(FSU: Florida State University)
Proper release of insulin from pancreatic islets of Langerhans is essential for maintaining glucose homeostasis. For full efficacy, both the pattern and the amount of hormone release are critical. It is therefore important to understand how insulin levels are secreted from single islets in both a quantitative fashion and in a manner that resolves temporal dynamics. In this study, we describe a microfluidic analytical system that can both quantitatively monitor insulin secretion from single islet...
2 Citations Source Cite