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Dietary macronutrient composition affects ? cell responsiveness but not insulin sensitivity.

ABSTRACT: Altering dietary carbohydrate or fat content may have chronic effects on insulin secretion and sensitivity, which may vary with individual metabolic phenotype.The objective was to evaluate the contribution of tightly controlled diets differing in carbohydrate and fat content for 8 wk to insulin sensitivity and ? cell responsiveness and whether effects of diet would vary with race, free-living diet, or insulin response.Healthy overweight men and women (36 European Americans, 33 African Americans) were provided with food for 8 wk and received either a eucaloric standard diet (55% carbohydrate, 27% fat) or a eucaloric reduced-carbohydrate (RedCHO)/higher-fat diet (43% carbohydrate, 39% fat). Insulin sensitivity and ? cell responsiveness were assessed at baseline and 8 wk by using a liquid meal tolerance test.Insulin sensitivity did not change with diet (P = 0.1601). Static ? cell response to glucose (?S) was 28.5% lower after the RedCHO/higher-fat diet. Subgroup analyses indicated that lower ?S with the RedCHO/higher-fat diet occurred primarily among African Americans. A significant inverse association was observed for change in glucose area under the curve compared with change in ?S.Consumption of a eucaloric 43% carbohydrate/39% fat diet for 8 wk resulted in down-regulation of ? cell responsiveness, which was influenced by baseline phenotypic characteristics. Further study is needed to probe the potential cause-and-effect relation between change in ?S and change in glucose tolerance. This trial is registered at clinicaltrials.gov as NCT00726908.

SUBMITTER: Goree LL

PROVIDER: S-EPMC3127518 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Dietary macronutrient composition affects β cell responsiveness but not insulin sensitivity.

Goree Laura Lee LL Chandler-Laney Paula P Ellis Amy C AC Casazza Krista K Granger Wesley M WM Gower Barbara A BA

The American journal of clinical nutrition 20110518 1

<h4>Background</h4>Altering dietary carbohydrate or fat content may have chronic effects on insulin secretion and sensitivity, which may vary with individual metabolic phenotype.<h4>Objective</h4>The objective was to evaluate the contribution of tightly controlled diets differing in carbohydrate and fat content for 8 wk to insulin sensitivity and β cell responsiveness and whether effects of diet would vary with race, free-living diet, or insulin response.<h4>Design</h4>Healthy overweight men and ...[more]

PMID: 21593507

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Project description:Carbohydrate response element binding protein (ChREBP) is a lipogenic transcription factor that is thought to be involved in the development of hepatic steatosis and insulin resistance. Increased ChREBP expression in liver results in increased hepatic steatosis, and the isoform ChREBP? in adipose tissue can predict insulin sensitivity in obese humans. As ChREBP is activated by glucose, it was postulated that the composition of diet would regulate ChREBP isoform expression in metabolically relevant tissues. We compared the effects of diets with high complex carbohydrate, high fat, or a normal chow on ChREBP expression and metabolic parameters in C57BL/6 mice. We found that diets high in fat decrease ChREBP expression in adipose tissue, but isocaloric diets high in carbohydrate have no effect. Interestingly, this decrease in adipose ChREBP was associated with increased inflammatory markers. In the same animals a high carbohydrate diet induced a robust increase in hepatic ChREBP? expression (?2-fold; p = 0.0002), but little detectable change in the more abundant ChREBP? transcript. This change was accompanied by increased expression of target genes liver pyruvate kinase (p<0.0001), acetyl-CoA carboxylase (p = 0.0191) and stearoyl-CoA desaturase-1 (p = 0.0045). This increase in ChREBP expression was associated with increased hepatic steatosis, despite no changes in body weight or body fat when compared to chow-fed mice. Unexpectedly, mice fed a high carbohydrate diet displayed enhanced sensitivity to exogenous insulin, despite having mild glucose intolerance and increased liver steatosis. In summary, we have shown the composition of diet can selectively regulate ChREBP isoform expression in a tissue specific manner. Furthermore, we have shown a high complex carbohydrate diet selectively increases hepatic ChREBP? expression, which associates with hepatic steatosis but not insulin resistance. In contrast, a high fat diet reduces adipose ChREBP, which associates with inflammation and insulin resistance.

Project description:BACKGROUND:We sought to characterize the effects of dietary macronutrient composition on various hormones implicated in the regulation of insulin sensitivity (IS) and energy expenditure (EE). METHODS:Following 10-15% weight loss, 21 overweight subjects consumed 3 weight-loss maintenance diets [low fat (LF), low glycemic index (LGI) and very low carbohydrate (VLC)] in random order, each for 4 weeks. At baseline and at the end of each treatment period, fasting samples for fibroblast growth factor (FGF)-21, heme-oxygenase-1 (HO-1), chemerin, irisin, secreted frizzle-related protein (SFRP-4), total bile acids, ghrelin, gastrin inhibitory peptide (GIP), peptide-Y, and amylin; hepatic and peripheral IS; and EE were obtained. Analyses were controlled for age, gender, baseline body mass index, and diet sequence. RESULTS:FGF-21 decreased (P < 0.0001), with differential effect by macronutrient composition (mean change from baseline ± SEM: LF -49.4 ± 16.6, LGI -58.6 ± 16.3, VLC -76.7 ± 18.2 pg/mL, P = 0.0002). Change in FGF-21 was inversely associated with change in hepatic IS [Beta = -0.565 units/log(ng/mL), P = 0.02], but not with peripheral IS or EE. Heme-oxygenase-1 (HO-1) increased (P = 0.003), without differential effect by macronutrient composition (LF 0.40 ± 0.26, LGI 0.98 ± 0.63, VLC 0.49 ± 0.29 ng/mL, P = 0.07). Ghrelin increased (P = 0.0003), while chemerin decreased (P = 0.001) without macronutrient effect. Total bile acid, irisin, SFRP-4, GIP, peptide-Y and amylin levels did not change. CONCLUSIONS:FGF-21 levels decreased with dietary intervention in proportion to carbohydrate content, and correlated with hepatic insulin sensitivity, suggesting a pattern of improving FGF-21 resistance. HO-1 increased in response to dietary intervention, a tendency to greater increase in response to the LGI diet. Dietary intervention affected ghrelin and chemerin, independent of macronutrient composition. These findings may elucidate relationships between dietary composition, insulin sensitivity and metabolism. TRIAL REGISTRATION:NCT00315354.

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Dietary macronutrient composition affects ? cell responsiveness but not insulin sensitivity.

Publications

Dietary macronutrient composition affects β cell responsiveness but not insulin sensitivity.

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