Effects of fat on insulin-stimulated carbohydrate metabolism in normal men.

Boden, Guenther; Jadali, Fayegh; White, John V.; Liang, Yin; Mozzoli, Maria; Chen, X; Coleman, Emily; Smith, Colleen M.

doi:10.1172/jci115399

Cited by 457 publications

(326 citation statements)

References 49 publications

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“…The circadian rhythm in cortisol is also unlikely to explain the lower glucose tolerance in the biological evening because cortisol, which decreases glucose tolerance (41,42), actually peaks in the biological morning and is low in the biological evening (10,15). Raised FFA levels can impair glucose tolerance and decrease insulin sensitivity and glucose oxidation (43)(44)(45). However, we found no effect of circadian phase on fasting or postprandial FFA levels.…”

Section: Discussionmentioning

confidence: 61%

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

Morris

Yang

Garcia

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

335

336

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Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/ feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show-by using two 8-d laboratory protocols-in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic β-cell function (27% lower earlyphase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers.circadian disruption | shift work | night work | glucose metabolism | diabetes I n healthy humans, there is a strong time-of-day variation in glucose tolerance, with a peak in the morning and a trough in the evening and night (1-6). Understanding the underlying mechanisms of the day/night variation in glucose tolerance is important for diurnally active individuals as well as shift workers, who are at increased risk for developing type 2 diabetes (7-9). The endogenous circadian system and circadian misalignment (i.e., misalignment between the endogenous circadian system and 24-h environmental/behavioral cycles) have been shown to affect glucose metabolism (4,(10)(11)(12)(13)(14). However, the relative and separate importance of the endogenous circadian system and circadian misalignment-after accounting for behavioral cycle effects (including the sleep/wake, fasting/feeding, and physical inactivity/activity cycles, etc.)-on 24-h variation in glucose tolerance is not well understood.Most species have evolved an endogenous circadian timing system that optimally times physiological variations and behaviors relative to the 24-h environmental cycle (15-17). The mammalian circadian system is comp...

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Section: Discussionmentioning

confidence: 61%

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

Morris

Yang

Garcia

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

335

336

View full text Add to dashboard Cite

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“…The rise in plasma levels of NEFAs has been shown to induce insulin resistance [5][6][7][8]. In line with these studies, it has been demonstrated that CD36 knockout mice have improved insulin sensitivity in muscle, implying that fatty acid flux into the cells plays a critical role in insulin resistance [9].…”

Section: Introductionmentioning

confidence: 80%

Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels

et al. 2005

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Aims/hypothesis: Elevated fasting and postprandial plasma levels of triglyceride-rich lipoproteins (TGRLs), i.e. VLDL/remnants and chylomicrons/remnants, are a characteristic feature of insulin resistance and are considered a consequence of this state. The aim of this study was to investigate whether intact TGRL particles are capable of inducing insulin resistance. Methods: We studied the effect of highly purified TGRLs on glycogen synthesis, glycogen synthase activity, glucose uptake, insulin signalling and intramyocellular lipid (IMCL) content using fully differentiated L6 skeletal muscle cells. Results: Incubation with TGRLs diminished insulin-stimulated glycogen synthesis, glycogen synthase activity, glucose uptake and insulin-stimulated phosphorylation of Akt and glycogen synthase kinase 3. Insulin-stimulated tyrosine phosphorylation of IRS-1, and IRS-1-and IRS-2-associated phosphatidylinositol 3-kinase (PI3K) activity were not impaired by TGRLs, suggesting that these steps were not involved in the lipoprotein-induced effects on glucose metabolism. The overall observed effects were time-and dose-dependent and paralleled IMCL accumulation. NEFA concentration in the incubation media did not increase in the presence of TGRLs indicating that the effects observed were solely due to intact lipoprotein particles. Moreover, co-incubation of TGRLs with orlistat, a potent active-site inhibitor of various lipases, did not alter TGRL-induced effects, whereas co-incubation with receptor-associated protein (RAP), which inhibits interaction of TGRL particles with members of the LDL receptor family, reversed the TGRL-induced effects on glycogen synthesis and insulin signalling. Conclusions/ interpretation: Our data suggest that the accumulation of TGRLs in the blood stream of insulin-resistant patients may not only be a consequence of insulin resistance but could also be a cause for it.

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“…In general, rapidly absorbed carbohydrates stimulate a large insulin rise, followed by a rapid blood glucose fall, often below baseline values. This could result in a counter-regulatory response with the release of free fatty acids, creating an insulin-resistant environment (Piatti et al, 1991;Boden et al, 1991) and reduced glucose tolerance. Ingestion of a slow release carbohydrate food (eg uncooked cornstarch) at bedtime was shown to produce a substantial suppression of nocturnal free fatty acid levels and postprandial improvements in breakfast glucose levels possibly due to reduced nocturnal lipolysis (Axelsen et al, 1997(Axelsen et al, ,1999a.…”

Section: Glycemic Index In Chronic Diseasementioning

confidence: 99%

Glycemic index in chronic disease: a review

et al. 2002

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Aim: The intent of this review is to critically analyze the scientific evidence on the role of the glycemic index in chronic Western disease and to discuss the utility of the glycemic index in the prevention and management of these disease states. Background: The glycemic index ranks foods based on their postprandial blood glucose response. Hyperinsulinemia and insulin resistance, as well as their determinants (eg high energy intake, obesity, lack of physical activity) have been implicated in the etiology of diabetes, coronary heart disease and cancer. Recently, among dietary factors, carbohydrates have attracted much attention as a significant culprit, however, different types of carbohydrate produce varying glycemic and insulinemic responses. Low glycemic index foods, characterized by slowly absorbed carbohydrates, have been shown in some studies to produce beneficial effects on glucose control, hyperinsulinemia, insulin resistance, blood lipids and satiety. Method: Studies on the short and long-term metabolic effects of diets with different glycemic indices will be presented and discussed. The review will focus primarily on clinical and epidemiological data, and will briefly discuss in vitro and animal studies related to possible mechanisms by which the glycemic index may influence chronic disease.

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Effects of fat on insulin-stimulated carbohydrate metabolism in normal men.

Cited by 457 publications

References 49 publications

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels

Glycemic index in chronic disease: a review

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