Regulation of glucose transport and transporter 4 (GLUT-4) in muscle and adipocytes of sucrose-fed rats: effects of N-3 poly- and monounsaturated fatty acids.

The goal of this study was to compare the short-term effects of dietary n-3 polyunsaturated (fish oil) and monounsaturated (olive oil) fatty acids on glucose transport, plasma glucose and lipid controls in a dietary insulin resistance model using sucrose-fed rats. The underlying cellular and molecular mechanisms were also determined in the muscle and adipose tissue. Male Sprague-Dawley rats (5 weeks old) were randomized for diets containing 57.5 % (w/w) sucrose and 14 % lipids as either fish oil (SF), olive oil (SO) or a mixture of standard oils (SC) for 3 weeks. A fourth control group (C) was fed a diet containing 57.5 % starch and 14 % standard oils. After three weeks on the diet, body weight was comparable in the four groups. The sucrose-fed rats were hyperglycemic and hyperinsulinemic in response to glucose load. The presence of fish oil in the sucrose diet prevented sucrose-induced hyperinsulinemia and hypertriglyceridemia, but had no effect on plasma glucose levels. Insulin-stimulated glucose transport in adipocytes increased after feeding with fish oil (p < 0.005). These modifications were associated with increased Glut-4 protein (p < 0.05) and mRNA levels in adipocytes. In the muscle, no effect was found on Glut-4 protein levels. Olive oil, however, could not bring about any improvement in plasma insulin, plasma lipids or Glut-4 protein levels. We therefore conclude that the presence of fish oil, in contrast to olive oil, prevents insulin resistance and hypertriglyceridemia in rats on a sucrose diet, and restores Glut-4 protein quantity in adipocytes but not in muscle at basal levels. Dietary regulation of Glut-4 proteins appears to be tissue specific and might depend on insulin stimulation and/or duration of dietary interventions.

Negative regulation of leptin by chronic high-glycemic index starch diet.

The response of plasma leptin to a high-glycemic index (high-GI) starch diet after a short (3 weeks) and prolonged (12 weeks) period was determined in Sprague-Dawley rats. Age-matched rats were fed an identical isocaloric diet except that the carbohydrates were from either mung bean starch (low-GI) or waxy cornstarch (high-GI). After a single test meal of the high-GI starch diet, postprandial plasma glucose (P < .05) and insulin (P < .01) peaks and plasma glucose (P < .014) and insulin (P < .05) areas were higher versus the low-GI starch diet (n = 8 per group). Other age-matched control rats were fed the same diets for a longer period. After 3 weeks, ob mRNA levels were decreased by 50% (P < .005) in the epididymal adipose tissue of high-GI-fed rats versus low-GI-fed rats, without a significant decrease in plasma leptin. After 12 weeks of the high-GI starch diet, both plasma leptin and ob mRNA were decreased by 34% (P < .005) and 41% (P < .05), respectively, compared with the low-GI diet. Both relative epididymal adipose tissue weight (adjusted per 100 g body weight) and total fat mass, as measured by dual-energy x-ray absorptiometry (DEXA), were unchanged by the high-GI starch diet. Basal nonfasting plasma insulin, glucose, and triglycerides were not altered by the high-GI starch diet, whereas free fatty acids were significantly elevated and associated with a trend (P < .13) for increased plasma free glycerol. Plasma leptin levels were negatively correlated with free fatty acid levels (r = .56, P < .05). Despite low leptin, rats fed on the high-GI diet did not increase their food intake, suggesting increased leptin sensitivity. These findings might precede weight gain and the increase in fat mass. Chronic nutritional factors might alter plasma leptin via several overlapping factors independently of energy intake.

A high glycemic index starch diet affects lipid storage-related enzymes in normal and to a lesser extent in diabetic rats.

The of this study was to evaluate the chronic effects of a high (waxy corn) vs. a low (mung beans) glycemic index starch diet on the lipogenic enzymes, fatty acid synthase (FAS) and lipoprotein lipase (LPL). Normal and diabetic (streptozotocin-injected on d 2 of life) male Sprague-Dawley rats consumed a diet containing 575 g/kg carbohydrates either as waxy cornstarch (WCS) or as mung bean starch (MBS). After 3 wk, neither body weights nor relative epididymal fat pad weights differed. In diabetic rats, the WCS diet induced high basal plasma insulin levels. Plasma triglycerides were not significantly affected by diet in either normal or diabetic rats. Adipose tissue and liver LPL activities were not modified by the type of starch in the diet. In normal rats, FAS activity and gene expression in epididymal adipose tissue but not in liver were greater in rats consuming the WCS diet than in those consuming MBS. To evaluate the implication of insulin in this regulation, two genes regulated by insulin [GLUT4 and phosphoenolpyruvate carboxykinase (PEPCK)] were also studied. The high glycemic index WCS diet compared with the low glycemic index MBS diet resulted in lower hepatic PEPCK mRNA in both normal and diabetic rats. Normal, but not diabetic rats fed WCS had greater GLUT4 gene expression in adipocytes than did those fed MBS. We conclude that the total replacement of 575 g/kg low glycemic index starch by a high glycemic index starch for 3 wk caused the following in normal rats: 1) high FAS activity and mRNA in adipose tissue but not in liver and 2) high GLUT4 gene expression in adipose tissue. In both normal and diabetic rats this same diet resulted in lower hepatic PEPCK mRNA. Therefore, high glycemic index starch diet is implicated in stimulating FAS activity and lipogenesis and might have undesirable long-term metabolic effects.

Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study.

OBJECTIVE: To evaluate the effect of a moderate dose of fish oil on glycemic control and in vivo insulin action in type 2 diabetic men with elevated plasma triacylglycerols and to determine the effect of the same treatment on gene expression of GLUT4, lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL) in the abdominal adipose tissue. RESEARCH DESIGN AND METHODS: A total of 12 type 2 diabetic men were randomly allocated to 2 months of 6 g daily of either fish oil or sunflower oil, separated by a 2-month washout interval, in a double-blind crossover design. RESULTS: For glucose metabolism, 2 months of fish oil supplementation compared with sunflower oil led to similar fasting plasma insulin, glucose, and HbA1c. Basal hepatic glucose production did not increase after fish oil. There was no difference in insulin suppression of hepatic glucose production nor in insulin stimulation of whole-body glucose disposal measured by the euglycemic-hyperinsulinemic clamp. Fish oil did not ameliorate the low mRNA level of GLUT4 in adipose tissue of these patients. For lipid profile, fish oil lowered plasma triacylglycerol more than sunflower oil (P < 0.05) and tended to increase the amount of mRNA of both LPL and HSL in adipose tissue. CONCLUSIONS: A moderate dose of fish oil did not lead to deleterious effects on glycemic control or whole-body insulin sensitivity in type 2 diabetic men, with preserved triacylglycerol-lowering capacities.

Dietary (n-3) polyunsaturated fatty acids improve adipocyte insulin action and glucose metabolism in insulin-resistant rats: relation to membrane fatty acids.

To study the effects of dietary fish oil on insulin-stimulated glucose metabolism in adipocytes of insulin-resistant rats (rats fed 50% sucrose and 30% fat), eighteen 5-wk-old Sprague-Dawley rats were fed, for 6 wk, a diet containing 30% fat as either fish oil (FO) or a mixture of vegetable and animal oils [control oils (CO)]. A third reference group was fed a standard diet (62% corn starch and 13% fat). At the end of the 6-wk period, the two experimental groups had comparable plasma glucose concentrations that were higher than that found in the reference group. FO feeding corrected the hyperinsulinemia of the experimental rats (P < 0.05) to reach values in the reference group. Plasma triacylglycerol (P < 0.01) and cholesterol (P < 0.001) concentrations were also lower in rats fed FO than in those fed CO. The body weights of FO-fed rats were similar to that of CO-fed rats, but epididymal adipose tissue weight was lower (P < 0.01). Adipocytes of FO-fed rats, compared with those of CO-fed rats, had high insulin-stimulated glucose transport (P < 0.05), oxidation (P < 0.001) and incorporation into total lipids (P < 0.05). The incorporation of (n-3) polyunsaturated fatty acids in adipocyte membrane phospholipids was higher in FO-fed rats than in those fed CO (P < 0.0001). Insulin action was positively correlated with the fatty acid unsaturation index in membrane phospholipids. Thus dietary fish oil has beneficial effects on insulinemia, plasma lipids and insulin-stimulated glucose metabolism in insulin-resistant slightly diabetic rats.

Effects of long-term low-glycaemic index starchy food on plasma glucose and lipid concentrations and adipose tissue cellularity in normal and diabetic rats.

The present study aimed to assess the metabolic consequences of the chronic ingestion of two starches giving different postprandial glycaemic responses in normal and diabetic rats. The two starches chosen were mung-bean (Phaseolus aureus) starch (97% pure starch) and wheat starch presented as ground French toast. First, we studied the characteristics of these two starches. In vitro the alpha-amylase (EC 3.2.1.1) digestibilities of these starches were 40 (SE 3) and 62 (SE 4)% respectively at 30 min, whereas the contents of resistant starch were 77 (SE 4) and 22 (SE 4) g/kg respectively. In vivo the mung-bean starch produced lower postprandial glycaemic responses than the wheat starch (areas under the curve were: 91 (SE 28) and 208 (SE 33) mmol.min/l, P < 0.05) in normal rats (n 8). We then submitted twenty-eight normal and twenty-eight diabetic (neonatal streptozotocin on second day of birth) male Sprague-Dawley rats (6 weeks old) to a diet containing 570 g starch/kg as either mung-bean starch or wheat starch (n 14 rats/group). After 5 weeks on the diets food intakes and body weights were identical in each group. Liver and kidney weights were comparable when expressed as relative weight. The mung-bean-starch diet slightly decreased epididymal fat-pad weight (P < 0.14, ANOVA) and led to a marked decrease in adipocyte volume (P < 0.05). Plasma triacylglycerol and phospholipid concentrations were lower after the mung-bean-starch diet than after the wheat-starch diet in both normal and diabetic rats, whereas free fatty acid concentrations were lower only in normal rats. Similarly, non-fasting plasma glucose concentrations decreased (P < 0.05) in normal rats fed on mung-bean starch but not in diabetic ones (P < 0.14). Insulin levels tended to be lower, but not significantly, after mung-bean-starch feeding than after wheat starch. We conclude that the replacement of 570 g wheat starch/kg diet with mung-bean starch for 5 weeks resulted in (1) lowered non-fasting plasma glucose and free fatty acid levels in normal but not in diabetic rats, (2) a reduction in plasma triacylglycerol concentration and adipocyte volume in both normal and diabetic rats. Thus, the type of starch mixed into the diet may have important metabolic consequences in normal and diabetic rats.

Effects of chronic dietary fructose with and without copper supplementation on glycaemic control, adiposity, insulin binding to adipocytes and glomerular basement membrane thickness in normal rats.

Sucrose feeding over a long period has been reported to induce glomerular basement membrane (GBM) thickening and insulin resistance in normal rats. These effects are attributed to the fructose moiety of the sucrose molecule, to Cu deprivation or both. Consequently, our aim was to evaluate the long-term effects of fructose feeding with normal or high amounts of Cu on body weight, plasma lipids, blood glucose regulation, GBM thickening and insulin binding to adipocytes. Four groups of eight Sprague-Dawley rats were fed for 10 weeks on a diet containing 570 g carbohydrate/kg supplied either as starch (S), dextrose (D), fructose (F) or fructose-starch (1:1, w/w; FS), and an adequate amount of Cu (12 micrograms Cu/g diet). A fifth group was fed on diet F supplemented with 24 micrograms Cu/g diet (FCu). After 10 weeks the epididymal adipose tissue and kidney weights expressed per 100 g body weight (relative weight) were heaviest in the F and FCu groups (P < 0.0001, ANOVA). The GBM thickness was within the normal range in the five groups but significantly higher in group D (1.95 (SE 0.04) nm and lower in group FS (1.79 (SE 0.02) nm when compared with group S (1.85 (SE 0.03) nm; P < 0.05). Insulin binding to adipocytes (expressed per cell) was lowest in the F and FCu groups, intermediate in groups D and FS and highest in group S (P < 0.05). Fasting plasma insulin level was higher in group F than in the FCu and FS groups (P < 0.05), whereas fasting plasma glucose, total cholesterol and triacylglycerol levels remained within the normal range in all groups. We conclude that in normal rats a 10-week fructose-rich diet with an adequate amount of Cu produced deleterious metabolic effects on adipose tissue, insulin binding to adipocytes, and plasma insulin, but not on GBM thickening even though kidney weight was significantly increased. However, a moderate fructose intake mixed with other sugars did not have adverse effects.