Free fatty acids increase basal hepatic glucose production and induce hepatic insulin resistance at different sites

Lam, Tony K.T.; Werve, Gérald van de; Giacca, Adria

doi:10.1152/ajpendo.00332.2002

Cited by 132 publications

(101 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, higher insulin concentrations would physiologically lead to larger postprandial suppression of NEFA unless the meal had caused a state of acute insulin resistance. NEFA derived from serum triglycerides are known to increase hepatic glucose production and induce hepatic insulin resistance (Lam et al, 2003). However, it occurs unlikely that WH-meal would induce acute postprandial insulin resistance within the initial 30 min.…”

Section: Discussionmentioning

confidence: 99%

Acute differential effects of milk-derived dietary proteins on postprandial lipaemia in obese non-diabetic subjects

et al. 2011

View full text Add to dashboard Cite

Background/Objectives: Postprandial lipaemia is an established risk factor for atherosclerosis. To investigate the acute effect of four milk-derived dietary proteins (alpha-lactalbumin, whey isolate, caseinoglycomacropeptide and whey hydrolysate) on postprandial lipaemia, we have conducted a randomized, acute, single-blinded clinical intervention study with crossover design. Subjects/Methods: A total of 11 obese non-diabetic subjects (age: 44-74, BMI: 30-41.4 kg m -2 ) were included. On 4 different days the subjects ingested a high-fat meal with the following energy distribution: 66% energy from fat (100 g of butter), 15% of energy from carbohydrate (90 g of white wheat bread) and 19% of energy from protein (45 g of pure protein). Our primary variable was plasma triglyceride measured in the 8-h postprandial period. Secondarily, retinyl palmitate, non-esterified free fatty acids, glucose, insulin, glucagon, GLP-1 and GIP, active and total grehlin and cholecystokinin were measured. Results: We observed no statistically significant (P ¼ 0.8) differences between meals on our primary variable that is, triglycerides. Whey hydrolysate was associated with a significantly (P ¼ 0.02) smaller postprandial suppression of non-esterified free fatty acids compared with the other dietary proteins. Conclusion: We did not observe significant differences in postprandial lipaemia to the four milk-derived dietary proteins. Whey hydrolysate caused less postprandial suppression of free fatty acids.

show abstract

Section: Discussionmentioning

confidence: 99%

Acute differential effects of milk-derived dietary proteins on postprandial lipaemia in obese non-diabetic subjects

et al. 2011

View full text Add to dashboard Cite

show abstract

“…These characteristics are similar to the human diabetic condition, and it may be that the pathology of diabetes in humans is adaptive in a species that fasts for long durations and exists on a diet high in lipid and protein but devoid of carbohydrate. Short-term elevations of plasma NEFA have been shown to induce hepatic and peripheral insulin resistance and possibly increase EGP (6,26,27). Conversely, under constant circulating concentrations of insulin, glucagon, and cortisol, hyperglycemia (200% basal levels) has been demonstrated to reduce rates of lipolysis by up to 30% (13).…”

Section: Discussionmentioning

confidence: 99%

Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals

Houser¹,

Champagne²,

Crocker³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Adult female elephant seals (Mirounga angustirostris) combine long-term fasting with lactation and molting. Glycerol gluconeogenesis has been hypothesized as potentially meeting all of the glucose requirements of the seals during these fasts. To test this hypothesis, a primed constant infusion of [2-14 C]glycerol was administered to 10 ten adult female elephant seals at 5 and 21-22 days postpartum and to 10 additional adult females immediately after the molt. Glycerol kinetics, rates of lipolysis, and the contribution of glycerol to glucose production were determined for each period. Plasma metabolite levels as well as insulin, glucagon, and cortisol were also measured. Glycerol rate of appearance was not significantly correlated with mass (P ϭ 0.14, r 2 ϭ 0.33) but was significantly related to the percentage of glucose derived from glycerol (P Ͻ 0.01, r 2 ϭ 0.81) during late lactation. The contribution of glycerol to glucose production was Ͻ3% during each fasting period, suggesting a lower contribution to gluconeogenesis than is observed in other long-term fasting mammals. Because of a high rate of endogenous glucose production in fasting elephant seals, it is likely that glycerol gluconeogenesis still makes a substantial contribution to the substrate needs of glucose-dependent tissues. The lack of a relationship between glucoregulatory hormones and glycerol kinetics, glycerol gluconeogenesis, and metabolites supports the proposition that fasting elephant seals do not conform to the traditional insulinglucagon model of substrate metabolism. reesterification; lipid metabolism; lactogenesis; glucagon; insulin GLUCONEOGENESIS IS an important physiological process in maintaining blood glucose levels during fasting and can meet Ͼ90% of glucose needs after just 2 days of fasting (28). Both amino acids and glycerol can be metabolized to glucose when exogenous carbohydrate becomes unavailable. However, under long-term fasting conditions the loss of protein is generally minimized to stay the eventual loss of organ function that results from protein depletion. Under these conditions glycerol becomes an increasingly important gluconeogenic precursor. In the postabsorptive state, the conversion of glycerol to glucose accounts for ϳ3-4.5% of glucose production; however, after fasting for several days, the contribution of glycerol to glucose production increases to ϳ10 -22% (2, 7, 29). After weeks of fasting glycerol can contribute up to 60% of glucose production (7), although the basis for this calculation has come into question because of methodological issues related to the separation of radiolabeled glycerol from radiolabeled glucose (2). Thus, during long-duration fasts, the availability of lipid stores not only serves to provide energy via fatty acid oxidation but also contributes to meeting the energetic costs of glucose-dependent tissues.Northern elephant seals (Mirounga angustirostris) undertake prolonged fasts of 1-3 mo. Adult females undertake two fasts each year, one while lactating and another while molting. Bot...

show abstract

“…Most women with PCOS present increased circulating levels of free fatty acids (FFAs), which have been shown to cause insulin resistance in vivo [79,80]. In fact, several in vivo studies demonstrated that elevating circulating FFAs leads to peripheral tissue insulin resistance [81][82][83]. Accumulation of plasma fatty acids in muscle and liver tissues induce mitochondrial dysfunction, oxidative stress, inflammation and immune disorders [84].…”

Section: Cellular Mechanisms Of Metabolic Insulin Resistance-mostmentioning

confidence: 99%

Insulin and hyperandrogenism in women with polycystic ovary syndrome

Baptiste

Battista

Trottier

et al. 2010

The Journal of Steroid Biochemistry and Molecular Biology

264

199

View full text Add to dashboard Cite

Polycystic ovary syndrome (PCOS) is a very common endocrine disorder characterized by chronic anovulation, clinical and/or biochemical hyperandrogenism, and/or polycystic ovaries. But most experts consider that hyperandrogenism is the main characteristic of PCOS. Several theories propose different mechanisms to explain PCOS manifestations: (1) a primary enzymatic default in the ovarian and/or adrenal steroidogenesis; (2) an impairment in gonadotropin releasing hormone (GnRH) secretion that promotes luteal hormone (LH) secretion; or (3) alterations in insulin actions that lead to insulin resistance with compensatory hyperinsulinemia. However, in the past 20 years there has been growing evidence supporting that defects in insulin actions or in the insulin signalling pathways are central in the pathogenesis of the syndrome. Indeed, most women with PCOS are metabolically insulin resistant, in part due to genetic predisposition and in part secondary to obesity. But some women with typical PCOS do not display insulin resistance, which supports the hypothesis of a genetic predisposition specific to PCOS that would be revealed by the development of insulin resistance and compensatory hyperinsulinemia in most, but not all, women with PCOS. However, these hypotheses are not yet appropriately confirmed, and more research is still needed to unravel the true pathogenesis underlying this syndrome. The present review thus aims at discussing new concepts and findings regarding insulin actions in PCOS women and how it is related to hyperandrogenemia.

show abstract

Free fatty acids increase basal hepatic glucose production and induce hepatic insulin resistance at different sites

Cited by 132 publications

References 52 publications

Acute differential effects of milk-derived dietary proteins on postprandial lipaemia in obese non-diabetic subjects

Acute differential effects of milk-derived dietary proteins on postprandial lipaemia in obese non-diabetic subjects

Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals

Insulin and hyperandrogenism in women with polycystic ovary syndrome

Contact Info

Product

Resources

About