Insulin inhibits apolipoprotein B secretion in isolated human hepatocytes

Salhanick, Arthur I.; Schwartz, Seymour I.; Amatruda, John M.

doi:10.1016/0026-0495(91)90109-a

Cited by 41 publications

(25 citation statements)

References 38 publications

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“…In line with this Cummings et al [9] observed no effect of insulin on VLDL apo B FCR in NIDDM subjects. In conclusion, we have uncovered an action of insulin on VLDL1 apo B metabolism in vivo that was postulated to occur on the basis of cell culture findings [29,30]. Teleologically, an acute action of insulin on the release of large triglyceride-rich lipoproteins from the liver helps preserve hepatic lipid stores at a time when there is abundant triglyceride present in the circulation in the form of chylomicrons i. e. it is a further 'anabolic' action of the hormone.…”

Section: Discussionmentioning

confidence: 86%

“…However, more recent cell culture work has provided clear evidence that the presence of insulin has 1 507 326 269 507 326 269 188 108 210 2 1086 1011 883 1086 1011 883 201 201 364 3 687 792 870 687 792 870 175 155 166 4 500 510 331 483 492 311 191 179 230 5 904 842 356 796 116 72 6 690 625 747 690 625 747 140 106 an inhibitory effect on VLDL synthesis and release [29,30]. Comparable investigations in humans have reported discrepant results.…”

Section: Discussionmentioning

confidence: 99%

“…The patients were admitted to the metabolic ward at the Helsinki University Central Hospital at 07. 30 hours. An indwelling cannula was inserted in an antecubital vein for infusions and a second cannula was inserted retrogradely into a heated hand vein to obtain arterialized venous blood for blood sampling.…”

Section: Methodsmentioning

confidence: 99%

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Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM

et al. 1997

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Features of diabetic dyslipidaemia in non-insulin-dependent diabetes mellitus (NIDDM), such as a low HDL cholesterol concentration, the preponderance of small dense LDL and postprandial fat intolerance are considered to be metabolic consequences of elevated plasma triglycerides [1]. The mechanism underlying hypertriglyceridaemia in NIDDM is still unclear. A majority of studies indicate that the elevation of plasma triglycerides in NIDDM result from an overproduction of VLDL triglyceride [2,3] and apo B [4,5] but it is unclear and a matter of controversy whether the increased production of VLDL particles is driven by a direct effect of hyperinsulinaemia or is a consequence of defective suppression of VLDL production by insulin [1]. In healthy subjects acute insulin administration suppresses VLDL apo B production [6][7][8]. Data on the suppression of VLDL production by insulin in insulin resistant states are controversial. Lewis et al. [6] showed an impaired suppression of VLDL apo B production in obese subjects while Cummings et al. [9] did not find any defect in the ability of insulin to suppress VLDL apo B production in patients with NIDDM.Two major subclasses of VLDL particles are recognised, large triglyceride-rich VLDL1 particles Diabetologia (1997) 40: 454-462 Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM Summary Insulin administration to healthy subjects inhibits the production of very low density lipoprotein (VLDL)1 (Svedbergs flotation (Sf) rate 60-400) without affecting that of VLDL2 (Sf 20-60) subclass. This study was designed to test whether this hormonal action is impaired in non-insulin-dependent diabetes mellitus (NIDDM). We studied six men with NIDDM (age 53 ± 3 years, body mass index 27.0 ± 1.0 kg/m 2 , plasma triglycerides 1.89 ± 0.22 mmol/l) during an 8.5 h infusion of saline (control) and then in hyperinsulinaemic (serum insulin ∼ 540 pmol/l) conditions during 8.5 h infusions of glucose and insulin to give either hyper-and normoglycaemic conditions. [3-2 H]-leucine was used as tracer and kinetic constants derived using a non-steadystate multicompartmental model. Compared to the control study, patients with NIDDM reduced VLDL1 apo B production by only 3 ± 8 % after 8.5 h of hyperinsulinaemia (701 ± 102 vs 672 ± 94 mg/day respectively, NS) in hyperglycaemic conditions and by 9 ± 21 % under normoglycaemic conditions (603 ± 145 mg/day). In contrast, in normal subjects insulin induced a 50 ± 15 % decrement in VLDL1 apo B production (p < 0.05). Direct synthesis of VLDL2 apo B in patients with NIDDM was not markedly affected by insulin. We conclude that a contributory factor to hypertriglyceridaemia in NIDDM is the inability of insulin to inhibit acutely the release of VLDL1 from the liver, despite efficient suppression of serum nonesterfied fatty acids. [Diabetologia (1997) 40: 454-462]

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

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Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM

et al. 1997

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“…Moreover, genetic disruption of hepatic insulin signaling in mice reduces triglyceride secretion, lowers serum TAG levels, and reduces atherogenesis in animal models (8)(9)(10). On the other hand, in isolated hepatocytes, insulin treatment inhibits VLDL-TAG and apolipoprotein B secretion (11,12). Therefore, there are conflicting reports on the role of hepatic insulin signaling in the control of VLDL secretion.…”

Section: Introductionmentioning

confidence: 99%

mTORC1 stimulates phosphatidylcholine synthesis to promote triglyceride secretion

Quinn¹,

Wan²,

Shewale³

et al. 2017

Journal of Clinical Investigation

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“…One possible mechanism to account for the lower postprandial change in overall total TAG concentration following lunch compared to breakfast is suppression of VLDL-TAG secretion by the liver. This is supported by the observation that addition of insulin to cultured cells (Durrington et al, 1982;Dashti & Wolfbauer, 1987;Sparks et al, 1989;Byrne et al, 1991;Salhanick et al, 1991) and acute hyperinsulinaemia in human subjects (Vogelberg et al, 1978;Lewis et al, 1993Lewis et al, , 1994Shumak et al, 1988;Malmstrom et al, 1997a) suppressed VLDL secretion. Furthermore, Malmstrom et al (1998) showed that hyperinsulinaemia suppressed secretion of VLDL 1 leading to a differential increase in VLDL 2 secretion.…”

Section: Discussionmentioning

confidence: 85%

Effect of meal sequence on postprandial lipid, glucose and insulin responses in young men

et al. 2003

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Objective: To investigate whether the postprandial changes in plasma triacylglycerol (TAG), nonesterified fatty acids (NEFA), glucose and insulin concentrations in young men were the same if an identical meal was fed at breakfast and lunch, and if the response to lunch was modified by consumption of breakfast. Methods: In two trials (1 and 2) healthy subjects (age 2271 y, body mass index 2272 kg/m 2 ) were fed the same mixed macronutrient meal at breakfast at 08:00 h and lunch at 14:00 h. In the third trial, no breakfast was fed and the overnight fast extended until lunch at 14:00 h. Addition of [1,1,1-13 C]tripalmitin to one meal in each trial was used to distinguish between endogenous and meal-derived lipids. Results: The postprandial changes in TAG, NEFA and glucose concentrations were similar in trials 1 and 2. The change in plasma total TAG concentration was about two fold less (Po0.05) after lunch compared to breakfast. Postprandial NEFA suppression was the same after breakfast and lunch. Glucose and insulin responses were significantly greater following lunch suggesting decreasing insulin sensitivity during the day. Consumption of breakfast did not alter the postprandial total TAG or NEFA responses after lunch. Measurement of [13 C]palmitic acid concentration showed that handling of TAG and NEFA from the meal was the same after breakfast and lunch, and was not altered by consumption of breakfast. Conclusions: Overall, these data suggest that in young, healthy men regulation of plasma TAG from endogenous sources, principally VLDL, but not chylomicrons during the postprandial period leads to differences in the magnitude of lipaemic response when the same meal was consumed at breakfast or at lunch 6 h later.

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Insulin inhibits apolipoprotein B secretion in isolated human hepatocytes

Cited by 41 publications

References 38 publications

Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM

Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM

mTORC1 stimulates phosphatidylcholine synthesis to promote triglyceride secretion

Effect of meal sequence on postprandial lipid, glucose and insulin responses in young men

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