Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese,hyperinsulinemic (JCR-LA corpulent) rats

Human studies suggest that chromium picolinate (CrPic) decreases insulin levels and improves glucose disposal in obese and type 2 diabetic populations. To evaluate whether CrPic may aid in treatment of the insulin resistance syndrome, we assessed its effects in JCR:LA-corpulent rats, a model of this syndrome. Male lean and obese hyperinsulinemic rats were randomly assigned to receive oral CrPic [80 microg/(kg. d); n = 5 or 6, respectively) in water or to control conditions (water, n = 5). After 3 mo, a 120-min intraperitoneal glucose tolerance test (IPGTT) and a 30-min insulin tolerance test were performed. Obese rats administered CrPic had significantly lower fasting insulin levels (1848 +/- 102 vs. 2688 +/- 234 pmol/L; P < 0.001; mean +/- SEM) and significantly improved glucose disappearance (P < 0.001) compared with obese controls. Glucose and insulin areas under the curve for IPGTT were significantly less for obese CrPic-treated rats than in obese controls (P < 0.001). Obese CrPic-treated rats had lower plasma total cholesterol (3.57 +/- 0.28 vs. 4.11 +/- 0.47 mmol/L, P < 0.05) and higher HDL cholesterol levels (1.92 +/- 0.09 vs. 1.37 +/- 0.36 mmol/L, P < 0.01) than obese controls. CrPic did not alter plasma glucose or cholesterol levels in lean rats. Total skeletal muscle glucose transporter (Glut)-4 did not differ among groups; however, CrPic significantly enhanced membrane-associated Glut-4 in obese rats after insulin stimulation. Thus, CrPic supplementation enhances insulin sensitivity and glucose disappearance, and improves lipids in male obese hyperinsulinemic JCR:LA-corpulent rats.     

Trans-11 vaccenic acid dietary supplementation induces hypolipidemic effects in JCR:LA-cp rats

Trans-11 vaccenic acid [VA; 18:1(n-9)] is a positional and geometric isomer of oleic acid and is the precursor to conjugated linoleic acid (CLA) in humans. Despite VA being the predominant trans monoene in ruminant-derived lipids, very little is known about its nutritional bioactivity, particularly in conditions of chronic metabolic disorders, including obesity, insulin resistance, and/or dyslipidemia. The aim of this study was to assess the potential of VA to improve dyslipidemia, insulin sensitivity, or inflammatory status in obese and insulin-resistant JCR:LA-cp rats. The obese rats and age-matched lean littermates were fed a control diet or a control diet supplemented with 1.5% (wt:wt) VA for a period of 3 wk. The incorporation of VA and subsequent conversion to CLA in triglyceride was measured in adipose tissue. Glucose and insulin metabolism were assessed via a conscious adapted meal tolerance test procedure. Plasma lipids as well as serum inflammatory cytokine concentrations were measured by commercially available assays. VA supplementation did not result in any observable adverse health effects in either lean or obese JCR:LA-cp rats. After 3 wk of feeding, body weight, food intake, and glucose/insulin metabolism did not differ between VA-supplemented and control groups. The incorporation of VA and CLA into adipose triglycerides in obese rats fed VA increased by 1.5-fold and 6.5-fold, respectively, compared with obese rats fed the control diet. The most striking effect was a 40% decrease (P < 0.05) in fasting triglyceride concentrations in VA-treated obese rats relative to obese controls. Serum Il-10 concentration was decreased by VA, regardless of genotype (P < 0.05). In conclusion, short-term dietary supplementation of 1.5% VA did not result in any detrimental metabolic effects in JCR:LA-cp rats. In contrast, dietary VA had substantial hypo-triglyceridemic effects, suggesting a new bioactivity of this fatty acid that is typically found in ruminant-derived food products.     

The effects of whey protein and chromium picolinate supplementation on visceral fat and metabolic status in high-fat-fed rats

The objective of this study was to evaluate the effects of whey protein (WP) and chromium picolinate (CrPic) on body composition and metabolic status in rats fed a high-fat diet (HFD). Male Wistar rats (n = 10/group, 8 weeks old) were divided into three groups. The control group was fed a HFD (300 g fat/kg diet). The other two groups were fed the HFD plus 320 g whey protein isolate/kg diet (HFD + WP) with or without 80 mcg CrPic/kg body wt/day (HFD + WP + CrPic). After six weeks, rats were fasted, blood samples were drawn, and visceral and subcutaneous fat pads were removed and weighed. Daily food intake was not affected by treatment. Rats fed HFD exhibited significant increases in body weight, body fat and metabolic risk factors (p ≤ 0.05). Rats fed the HFD + WP showed a significant decrease in body weight, serum glucose and blood lipids, and a significant increase in insulin levels (p ≤ 0.05). Rats fed the HFD + WP + CrPic had the lowest levels in total visceral fat, triglycerides, total cholesterol and free fatty acids, and the highest insulin levels (p ≤ 0.05). Tissue concentrations of chromium (Cr) increased with CrPic supplementation (p < 0.001). The results of this study support the use of WP and CrPic supplementation to improve body composition and metabolic syndrome risk factors.     

Insulin resistant glucose transport activity in adipose cells from the SHR/N-corpulent rat

Young male obese (cp/cp) and lean (cp/+ or +/+) littermates of the SHR/N-corpulent (cp) strain were fed purified diets containing 54% carbohydrate as either sucrose or cooked starch for 12 wk. A significant effect of phenotype (obese greater than lean) was observed on body weight, epididymal fat pad weight and fat cell size. A diet effect (sucrose greater than starch) was observed on body weight, fat pad weight, and fat cell size. No effect of phenotype or diet was observed on basal 3-O-methylglucose transport in isolated adipose cells. However, insulin-stimulated glucose uptake was decreased 70-80% in isolated adipose cells from obese SHR/N-cp rats. No effect of diet on insulin-stimulated glucose uptake was observed in obese SHR/N-cp rats. Scatchard analysis of insulin binding data demonstrated no differences in the dissociation constant (KD) for the insulin receptor:insulin complex. However, obese rats exhibited a decreased number of insulin receptors compared to lean SHR/N-cp rats. These data demonstrate that the obese SHR/N-cp rat exhibits insulin-resistant glucose transport. This altered insulin sensitivity may be one factor contributing to the development of noninsulin-dependent diabetes mellitus in these animals.     

Energy restriction reduces fractional calcium absorption in mature obese and lean rats

Weight loss is associated with bone loss and the risk may be greater in lean than heavier individuals, but the mechanisms involved remain unclear. We hypothesized that energy restriction (EnR) would decrease true fractional Ca absorption (TFCA) and be mediated by Ca-regulating hormones, but differently in obese and lean rats. Rats were fed a high fat (47% energy) or low fat (16% energy) diet for 4 mo. At 6 mo of age, the resulting lean [284 +/- 28g (mean +/- SD, n = 18)] and obese (319 +/- 34g, n = 20) groups (P < 0.005) were divided into controls (CTL, ad libitum) and energy-restricted (40% restriction) groups. At baseline, bone resorption (urinary crosslinks) was higher and bone formation (serum osteocalcin) was lower in obese than in lean rats, whereas Ca balance components and Ca-regulating hormones did not differ. EnR for 10 wk reduced body weight by 25 +/- 7% compared with a 6 +/- 6% gain in CTL rats (P < 0.001). For both lean and obese rats, TFCA (5-d measurement, (45)Ca radioisotope) decreased from 30 +/- 9% to 24 +/- 9% with EnR, compared with 25 +/- 10% to 29 +/- 11% in controls (P < 0.05). Weight loss was directly correlated with the decrease in TFCA (r = 0.34, P < 0.05). Uterine weights indicated a reduced estrogenic activity in energy-restricted rats (P < 0.0001). In lean, but not obese rats, serum estradiol (E(2)) correlated with weight loss (r = 0.52, P < 0.05), and tended to correlate with the decrease in TFCA (r = 0.48, P = 0.06). At the end of the study, serum 25-hydroxyvitamin-D was lower and urinary Ca was higher in lean than obese energy-restricted rats. Distinct endocrine profiles during weight loss in obese and lean rats suggest that the susceptibility of bone and Ca metabolism to EnR could differ depending on initial body weight.     

The male obese Wistar diabetic fatty rat is a new model of extreme insulin resistance

The male obese Wistar Diabetic Fatty (WDF) rat is a genetic model of obesity and non-insulin dependent diabetes (NIDDM). The obese Zucker rat shares the same gene for obesity on a different genetic background but is not diabetic. This study evaluated the degree of insulin resistance in both obese strains by examining the binding and post binding effects of muscle insulin receptors in obese rats exhibiting hyperinsulinemia and/or hyperglycemia. Insulin receptor binding and affinity and tyrosine kinase activity were measured in skeletal muscle from male WDF fa/fa (obese) and Fa/? (lean) and Zucker fa/fa (obese) and Fa/Fa (homozygous lean) rats. Rats were fed a high sucrose (68% of total Kcal) or Purina stock diet for 14 weeks. At 27 weeks of age, adipose depots were removed for adipose cellularity analysis and the biceps femoris muscle was removed for measurement of insulin binding and insulin-stimulated receptor kinase activity. Plasma glucose (13.9 vs. 8.4 mM) and insulin levels (14,754 vs. 7440 pmol/L) were significantly higher in WDF obese than in Zucker obese rats. Insulin receptor number and affinity and TK activity were unaffected by diet. Insulin receptor number was significantly reduced in obese WDF rats ( 2.778 +/- 0.617 pmol/mg protein), compared to obese Zucker rats (4.441 +/- 0.913 pmol/mg potein). Both obese strains exhibited down regulation of the insulin receptor compared to their lean controls. Maximal tyrosine kinase (TK) activity was significantly reduced in obese WDF rats (505 +/- 82 fmol/min/mg protein) compared to obese Zucker rats (1907 +/- 610 fmol/min/mg protein). Only obese WDF rats displayed a decrease in TK activity per receptor. These observations establish the obese WDF rat as an excellent model for exploring mechanisms of extreme insulin resistance, particularly post-receptor tyrosine kinase-associated defects, in non-insulin dependent diabetes.     

Increased A-ring reduction of glucocorticoids in obese Zucker rats: effects of insulin sensitization

OBJECTIVE: Obesity is associated with altered glucocorticoid metabolism, which may impact on hypothalamic-pituitary-adrenal axis activity. Here we characterize hepatic 5alpha- and 5beta-reductase in obese rats and their responses to insulin sensitization. RESEARCH METHODS AND PROCEDURES: Hepatic A-ring reductase protein and mRNA were assessed in lean and obese Zucker rats after insulin sensitization with metformin or rosiglitazone (n = 7 to 8/group). RESULTS: Hepatic 5alpha-reductase 1 and 5beta-reductase mRNA and protein (p < 0.01) were increased in obese rats. Insulin sensitization ameliorated increased 5alpha-reductase 1 mRNA in obese rats (p < 0.01) and partially reversed increased 5beta-reductase activity. DISCUSSION: Hepatic clearance of glucocorticoids by 5alpha- and 5beta-reductase is increased in obese Zucker rats, and this increase in clearance is attenuated by insulin sensitization. This increased hepatic clearance may underpin compensatory activation of the hypothalamic-pituitary-adrenal axis in obesity.     

饮食对胰岛素抵抗大鼠肝脏组织中PTP 1B表达的影响

目的在高脂饮食诱导胰岛素抵抗的基础上,观察饮食对大鼠肝脏中蛋白酪氨酸磷酸酶1B(PTP1B)表达的影响.方法选取雄性Wistar大鼠30只,随机分为正常对照组10只,给予基础饲料;模型组20只,给予高脂饲料.模型组大鼠给予高脂喂养4周后,随机分为2亚组胰岛抵抗组,继续高脂饮食;饮食组,给予低脂饮食干预.干预6周后,用蛋白印迹法检测各组大鼠肝组织中PTP1B蛋白含量.结果在胰岛素抵抗状态时,大鼠肝组织中PTP1B蛋白与对照组相比,含量增加98.3%(t=9.335,P＜0.001);饮食干预能明显降低PTP1B的表达,与胰岛素抵抗组相比减少32.7%(t=4.076,P＜0.001).结论饮食干预能改善机体胰岛素抵抗,可能与降低肝脏组织中PTP1B蛋白表达有关.     

Improved cognitive-cerebral function in older adults with chromium supplementation

Abstract

Insulin resistance is implicated in the pathophysiological changes associated with Alzheimer's disease, and pharmaceutical treatments that overcome insulin resistance improve memory function in subjects with mild cognitive impairment (MCI) and early Alzheimer's disease. Chromium (Cr) supplementation improves glucose disposal in patients with insulin resistance and diabetes. We sought to assess whether supplementation with Cr might improve memory and neural function in older adults with cognitive decline. In a placebo-controlled, double-blind trial, we randomly assigned 26 older adults to receive either chromium picolinate (CrPic) or placebo for 12 weeks. Memory and depression were assessed prior to treatment initiation and during the final week of treatment. We also performed functional magnetic resonance imaging (fMRI) scans on a subset of subjects. Although learning rate and retention were not enhanced by CrPic supplementation, we observed reduced semantic interference on learning, recall, and recognition memory tasks. In addition, fMRI indicated comparatively increased activation for the CrPic subjects in right thalamic, right temporal, right posterior parietal, and bifrontal regions. These findings suggest that supplementation with CrPic can enhance cognitive inhibitory control and cerebral function in older adults at risk for neurodegeneration.     

Adiponectin levels during low- and high-fat eucaloric diets in lean and obese women

OBJECTIVE: Adiponectin influences insulin sensitivity (S(I)) and fat oxidation. Little is known about changes in adiponectin with changes in the fat content of eucaloric diets. We hypothesized that dietary fat content may influence adiponectin according to an individual's SI. RESEARCH METHODS AND PROCEDURES: We measured changes in adiponectin, insulin, glucose, and leptin in response to high-fat (HF) and low-fat (LF) eucaloric diets in lean (n = 10) and obese (n = 11) subjects. Obese subjects were further subdivided in relation to a priori SI. RESULTS: We found significantly higher insulin, glucose, and leptin and lower adiponectin in obese vs. lean subjects during both HF and LF. The mean group values of these measurements, including adiponectin (lean, HF 21.9 +/- 9.8; LF, 20.8 +/- 6.6; obese, HF 10.0 +/- 3.3; LF, 9.5 +/- 2.3 ng/mL; mean +/- SD), did not significantly change between HF and LF diets. However, within the obese group, the insulin-sensitive subjects had significantly higher adiponectin during HF than did the insulin-resistant subjects. Additionally, the change in adiponectin from LF to HF diet correlated positively with the obese subjects' baseline SI. DISCUSSION: Although in lean and obese women, group mean values for adiponectin did not change significantly with a change in fat content of a eucaloric diet, a priori measured SI in obese subjects predicted an increase in adiponectin during the HF diet; this may be a mechanism that preserves SI in an already obese group.     

Chromium supplementation can alleviate negative effects of heat stress on egg production,egg quality and some serum metabolites of laying Japanese quail

This study was conducted to determine the effects of Cr (chromium picolinate, CrPic) supplementation at various levels (0, 200, 400, 800 or 1200 microg/kg of diet) on egg production, egg quality and serum concentrations of insulin, corticosterone and glucose in laying Japanese quail (Coturnix coturnix japanica) reared under conditions of heat stress (32.5 degrees C). Laying Japanese quail (n = 150; 45 d old) were divided into five groups of 30 birds. The quail were fed either a control diet containing 965 microg Cr/kg diet or the control diet supplemented with 200, 400, 800 or 1200 microg of Cr/kg diet. Increased supplemental chromium increased body weight (P = 0.05, linear), feed intake (P = 0.05, linear), egg production (P = 0.01, linear) and also improved feed efficiency (P = 0.01, linear). Increased supplemental chromium linearly increased egg weight (P = 0.01), eggshell thickness, egg specific gravity (P = 0.05) and Haugh unit (P = 0.01). Serum insulin concentration increased linearly (P = 0.01), whereas corticosterone and glucose concentration decreased linearly (P = 0.05) as dietary chromium increased. The best results were obtained with 1200 microg Cr/kg diet, and chromium supplementation at such a level can be considered to be protective management practice in a quail diet, reducing the negative effects of heat stress.     

Intraventricular insulin reduces food intake and body weight of lean but not obese Zucker rats

Porcine insulin (2 mU/rat/day) and its saline vehicle were infused into the third cerebral ventricle of female lean or obese Zucker rats using 14-day osmotic minipumps. Lean rats receiving saline (N = 6) gained 14 +/- 3 g over the 14 days, whereas lean rats receiving insulin (N = 7) lost 12 +/- 4 g over the same interval (p less than 0.01). The average total food intake of the insulin-infused group was decreased by 14% (p less than 0.05) as compared with that of the saline-infused group. The decreased caloric consumption was adequate to account for the body weight loss. Insulin infusion had no effect on food intake or body weight of the obese rats relative to their saline-infused controls (change in body weight: saline (N = 5), -14 +/- 23 g; insulin (N = 7), +3 +/- 14 g). These results suggest that genetically obese Zucker rats have reduced sensitivity to insulin in the central nervous system. We propose that this phenomenon may participate in the development and maintenance of hyperphagia and obesity in these animals.     

Vaccenic and elaidic acid modify plasma and splenocyte membrane phospholipids and mitogen-stimulated cytokine production in obese insulin resistant JCR: LA-cp rats

This study assessed the long-term effects of dietary vaccenic acid (VA) and elaidic acid (EA) on plasma and splenocyte phospholipid (PL) composition and related changes in inflammation and splenocyte phenotypes and cytokine responses in obese/insulin resistant JCR:LA-cp rats. Relative to lean control (Ctl), obese Ctl rats had higher serum haptoglobin and impaired T-cell-stimulated cytokine responses. VA and EA diets improved T-cell-stimulated cytokine production; but, only VA normalized serum haptoglobin. However, EA- and VA-fed rats had enhanced LPS-stimulated cytokine responses. The changes elicited by VA were likely due changes in essential fatty acid composition in PL; whereas EA-induced changes may due to direct incorporation into membrane PL.     

Specific preservation of biosynthetic responses to insulin in adipose tissue may contribute to hyperleptinemia in insulin-resistant obese mice

Obesity is characterized by whole-body insulin resistance, yet the expression of many insulin-stimulated genes, including leptin, is elevated in obesity. These observations suggest that insulin resistance may depend on tissue type and gene. To address this hypothesis, we examined the regulation of immediate-early gene expression in liver and adipose tissue after injection of insulin and glucose, in lean insulin-sensitive, and in A(y)/a obese insulin-sensitive and obese insulin-resistant mice. Expression of hepatic jun-B mRNA was robustly increased after insulin injection in lean insulin-sensitive a/a mice and insulin-sensitive A(y)/a mice. In contrast, induction of hepatic jun-B and c-fos gene expression by insulin was markedly attenuated in obese insulin-resistant mice. Surprisingly, induction of adipose jun-B and c-fos gene expression by insulin was markedly enhanced in obese insulin-resistant mice. Furthermore, the expressions of jun-B and leptin were also enhanced in insulin-resistant mice after injection of glucose. Leptin mRNA was positively correlated with blood glucose levels and jun-B mRNA in lean but not insulin-resistant mice. Multiple regression analysis indicated that the correlation between leptin mRNA and jun-B mRNA was significant even after removing the effect of blood glucose, but the correlation between leptin mRNA and glucose was no longer significant after removing the effect of jun-B mRNA. These data suggest that some impairments in biosynthetic responses to insulin are manifest primarily in the liver, leading to hyperinsulinemia and stimulating the expression of some adipose insulin-stimulated genes, including leptin. These studies demonstrate the utility of immediate-early gene expression in the analysis of biosynthetic mechanisms of insulin resistance.     

Liver insulin receptor tyrosine kinase activity in a rat model of type II diabetes mellitus and obesity

Spontaneous hypertensive-corpulent rats (SHR/N-corpulent), homozygous for the corpulent gene (cp/cp), are obese, hyperinsulinemic and exhibit abnormal glucose tolerance and thus represent a model for type II diabetes and obesity. In view of their overall insulin resistance, we examined liver insulin receptor binding and tyrosine kinase activity from corpulent rats and lean littermates fed purified diets containing 54% sucrose or starch for about 12 wk. Specific 125I-insulin binding to crude liver membranes from female corpulent rats fed either starch or sucrose was reduced to approximately 50% of that seen in lean rats (14 vs. 7%). Affinity of insulin receptors was similar in all groups, suggesting that hyperinsulinemic corpulent rats possess fewer hepatic insulin receptors than do lean rats. Using similar numbers of wheat germ agglutinin-agarose (WGA)-purified insulin receptors with similar affinities for insulin, it was found that basal and insulin-stimulated phosphorylation of the synthetic tyrosine-specific kinase substrate poly(Glu, Tyr)4:1 was similar in lean and obese rats fed sucrose or starch. It is suggested that the contribution of the liver to the insulin resistance in obese SHR/N-cp rats probably lies distal to the insulin receptor tyrosine kinase.     

The association between plasma adiponectin and insulin sensitivity in humans depends on obesity

OBJECTIVE: In humans, low plasma adiponectin concentrations precede a decrease in insulin sensitivity and predict type 2 diabetes independently of obesity. However, it is possible that the contribution of adiponectin to insulin sensitivity is not equally strong over the whole range of obesity. RESEARCH METHODS AND PROCEDURES: We investigated the cross-sectional association between plasma adiponectin levels and insulin sensitivity in different ranges of body fat content [expressed as percentage of body fat (PFAT)] in a large cohort of normal glucose-tolerant subjects (n = 900). All individuals underwent an oral glucose tolerance test (OGTT), and 299 subjects additionally a euglycemic hyperinsulinemic clamp. In longitudinal analyses, the association of adiponectin at baseline with change in insulin sensitivity was investigated in a subgroup of 108 subjects. RESULTS: In cross-sectional analyses, the association between plasma adiponectin and insulin sensitivity, adjusted for age, gender, and PFAT, depended on whether subjects were lean or obese [p for interaction adiponectin x PFAT = <0.001 (OGTT) and 0.002 (clamp)]. Stratified by quartiles of PFAT, adiponectin did not correlate significantly with insulin sensitivity in subjects in the lowest PFAT quartile (R2 = 0.10, p = 0.13, OGTT; and R2 = 0.10, p = 0.57, clamp), whereas the association in the upper PFAT quartile was rather strong (R2 = 0.36, p < 0.0001, OGTT; and R2 = 0.48, p = 0.003, clamp). In longitudinal analyses, plasma adiponectin at baseline preceded change in insulin sensitivity in obese (n = 54, p = 0.03) but not in lean (n = 54, p = 0.68) individuals. DISCUSSION: These data suggest that adiponectin is especially critical in sustaining insulin sensitivity in obese subjects. Thus, interventions to reduce insulin resistance by increasing adiponectin concentrations may be effective particularly in obese, insulin-resistant individuals.     

Delayed Onset of Ataxia in a Patient with Short Bowel Syndrome: A Case of Vitamin E Deficiency

Lean and obese Zucker rats were deprived of food for 12, 24, and 48 h. After sacrifice, plasma and brain tissue were saved for hormone and regional hypothalamic monoamine analysis. An ad libitum group was killed at time 0 for comparison to the food deprived groups. Insulin (I), C-peptide (CP), glucose, and the CP/I ratio were dramatically different across phenotype. Glucagon was only different at 12 h of caloric deprivation. Insulin secretion dropped substantially with fasting as reflected by the decrease in C-peptide plasma levels in both lean and obese rats. The CP/I ratio, which indicates clearance of insulin, increased in lean rats across time of fasting but did not significantly change in obese rats. Several distinct changes occurred between phenotypes in the hypothalamus across food deprivation. Lateral hypothalamic 5HT content and 5HT turnover (5HIAA/5HT) increased in lean but not obese rats during the period of fasting. Likewise ventromedial hypothalamic dopamine turnover (NE/DA) decreased during caloric deprivation in lean rats but not in the obese rats. This same turnover was increased in the PVNA of obese but not lean rats during caloric deprivation. Individual measurements of both C-peptide and insulin correlated significantly with LH 5HT turnover and VMH dopamine turnover in lean rats but not obese rats. These data suggest that obese rat's hypothalami may possibly be insensitive to insulin or some factor such as leptin that insulin may regulate. Because obese rats cannot change their levels of hypothalamic neurotransmitters when insulin or some other insulin induced factor changes, may suggest clues as to why these rats became obese. Perhaps these data may help explain the altered body weight set-point, increased adiposity, and hyperphagia in these animals.     

Effects of short-term dehydroepiandrosterone treatment on serum and pancreatic insulin in Zucker rats

Lean and obese female Zucker rats were treated with 0.6% dehydroepiandrosterone (DHEA) from 5 until 10 wk of age and comparisons made to both ad libitum--fed and weight-matched groups. Within genotype, body weights and cumulative food intakes of DHEA and weight-matched groups were not different. Fat pad weights of DHEA rats were significantly lower than those of non-treated groups. Pancreatic insulin content, whether expressed per pancreas or per gram pancreas, was not lowered by DHEA treatment. Fasting serum insulin levels were not altered in lean rats but were significantly lower in DHEA obese rats than in either nontreated obese group. Glucose metabolism (conversion to CO2, fatty acids or glyceride-glycerol) in isolated adipocytes was similar in all groups except that obese rats had greater glyceride-glycerol production than lean rats. Glucose conversion to CO2 in soleus muscle was lower in obese rats than in lean rats. Basal and insulin-stimulated glycogen production was lower in DHEA and weight-matched obese rats than in any other group. Ad libitum-fed lean rats had higher insulin-stimulated glycogen production than DHEA lean and all groups of obese rats. Short-term DHEA treatment of obese Zucker rats lowers serum insulin levels without improvement of insulin resistance in peripheral tissues and without lowering pancreatic insulin content.     

Effect of dietary carbohydrates on glucagon and insulin receptors in genetically obese female Zucker rats

Obese Zucker rats are hyperlipemic and mildly hyperglycemic. Because insulin and glucagon are involved in lipid and carbohydrate metabolism and they act via their receptors, we investigated the role of insulin and glucagon receptors in obese and lean female Zucker rats. Because dietary sucrose is more lipogenic than starch, we also studied the effect of dietary carbohydrates on the receptors. Significant phenotypic effect (obese greater than lean) was observed on plasma levels of glucose, triglyceride and insulin. Binding of insulin and glucagon to liver plasma membranes was significantly lower in obese rats than in lean rats. Lower insulin binding was due to a lower number of receptors as well as a lower affinity, whereas the lower glucagon binding was due only to a lower receptor number. Insulin binding in lean rats but not in obese rats was lower in sucrose-fed than in starch-fed rats. Diet had no effect on glucagon binding. We propose that in obese Zucker rats, in addition to hyperinsulinemia, impaired glucagon activity as manifested by decreased glucagon binding to target tissues may be an important contributor to the hyperlipemia and obesity.     

Food fried in extra-virgin olive oil improves postprandial insulin response in obese, insulin-resistant women

The benefits of low glycemic load (GL) diets on clinical outcome in several metabolic and cardiovascular diseases have extensively been demonstrated. The GL of a meal can be affected by modulating the bioavailability of carbohydrates or by changing food preparation. We investigated the effect on plasma glucose and insulin response in lean and obese women of adding raw or fried extra-virgin olive oil to a carbohydrate-containing meal. After an overnight fast, 12 obese insulin-resistant women (body mass index [BMI], 32.8?±?2.2?kg/m(2)) and five lean subjects (BMI, 22.2?±?1.2?kg/m(2)) were randomly assigned to receive two different meals (designated A and B). Meal A was composed of 60?g of pasta made from wheat flour and 150?g of grilled courgettes with 25?g of uncooked oil. Meal B included 15?g of oil in the 150?g of deep-fried courgettes and 10?g of oil in the 60?g of stir-fried pasta. Both meals included 150?g of apple. Blood samples were collected at baseline and every 30 minutes over a 3-hour post-meal period and were tested for levels of glucose, insulin, C-peptide, and triglycerides. The area under the curve (AUC) values were calculated. In obese women the AUCs for C-peptide were significantly higher after meal A than after meal B at 120 minutes (W [Wilcoxon sign rank test]?=?27.5, P?=?.0020), 150 minutes (W?=?26.5, P?=?.0039), and 180 minutes (W?=?26.5, P?=?.0039). No differences were found in lean subjects. This study demonstrated that in obese, insulin-resistant women, food fried in extra-virgin olive oil significantly reduced both insulin and C-peptide responses after a meal.